subject:(recessive)

Texas A&M University

1. Kondru, Vijaya. The Impact of Hypophosphatemia on Chondrocyte Fate.

Degree: MS, Oral Biology, 2017, Texas A&M University

URL: http://hdl.handle.net/1969.1/165846

► Dentin Matrix Protein 1(DMP1) is a non-collagenous phosphoprotein, belonging to the Small Integrin small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, the deficiency or mutation of… (more)

▼ Dentin Matrix Protein 1(DMP1) is a non-collagenous phosphoprotein, belonging to the Small Integrin small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, the deficiency or mutation of which results in Autosomal Recessive Hypophosphatemic Rickets, as evidenced by the accumulation of hypertrophic chondrocytes, resulting in immature or “premature” bone formation and mineralization. We employed cell lineage tracing (AggcretoDMP1-/-) together with other techniques to analyze the skeletal phenotype in DMP1 null mice at P10; these mice had shortened long bones and decreased circulatory levels of phosphate. While exogenous phosphate administration, in vitro, appeared to rescue the phenotype, we observed increased expressions of collagen 1 and osteopontin, together with high alkaline phosphatase activity (ALP) in the bone matrix, suggesting that these “accumulated” cells are actively differentiating into bone cells and secreting bone matrix; moreover, these bone cells were immature, and actively dividing, as indicated by decreased sclerostin (SOST) expression and increased Ki67 levels, respectively. However, while there was no apparent change in collagen 2 (Col2) and collagen 10 (Col10) expression, and Endomucin activity, Osterix and Runx2 levels were higher in the DMP1 control than in the KO. In conclusion, there is increased chondrogenesis in a “hypophosphate” environment in DMP1 null mice; here, hypertrophic chondrocytes “persist” and differentiate rapidly into immature bone cells (they do not apoptose as previously believed). While exogenous phosphate positively influenced the secondary ossification center in long bones, further studies at different time points are necessary to demonstrate such an effect. Moreover, to demonstrate the influence of phosphate rich diet on phenotype, cell lineage tracing studies are warranted to study the cell transformation from chondrocytes to bone cells. Advisors/Committee Members: Feng, Jerry (advisor), Opperman, Lynne (committee member), Jing, Yan (committee member).

Subjects/Keywords: DMP1; Autosomal Recessive Hypophosphatemic Rickets; SIBLING proteins

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APA (6^th Edition):

Kondru, V. (2017). The Impact of Hypophosphatemia on Chondrocyte Fate. (Masters Thesis). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/165846

Chicago Manual of Style (16^th Edition):

Kondru, Vijaya. “The Impact of Hypophosphatemia on Chondrocyte Fate.” 2017. Masters Thesis, Texas A&M University. Accessed March 08, 2021. http://hdl.handle.net/1969.1/165846.

MLA Handbook (7^th Edition):

Kondru, Vijaya. “The Impact of Hypophosphatemia on Chondrocyte Fate.” 2017. Web. 08 Mar 2021.

Vancouver:

Kondru V. The Impact of Hypophosphatemia on Chondrocyte Fate. [Internet] [Masters thesis]. Texas A&M University; 2017. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/1969.1/165846.

Council of Science Editors:

Kondru V. The Impact of Hypophosphatemia on Chondrocyte Fate. [Masters Thesis]. Texas A&M University; 2017. Available from: http://hdl.handle.net/1969.1/165846

Queen Mary, University of London

2. Bland, Philip James. The genetic and functional role of ABCA12 in Harlequin Ichthyosis.

Degree: PhD, 2016, Queen Mary, University of London

URL: http://qmro.qmul.ac.uk/xmlui/handle/123456789/12571 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.775189

► Harlequin Ichthyosis (HI) is the most severe disorder in the family of autosomal recessive congenital ichthyosis (ARCI). Recessive mutations in the ABC transporter ABCA12 were… (more)

▼ Harlequin Ichthyosis (HI) is the most severe disorder in the family of autosomal recessive congenital ichthyosis (ARCI). Recessive mutations in the ABC transporter ABCA12 were found to be causative in HI. Loss of ABCA12 leads to defective transport of ceramides, impaired transportation of proteases, premature terminal differentiation, transepidermal water loss (TEWL) and the retention of squames, which leads to the characteristic clinical phenotype of thickened hyperkeratotic plates overlying the skin. This thesis focuses on the genetic and functional role of ABCA12 in the skin and how loss of ABCA12 leads to the HI epidermis. Several molecular genetic techniques were utilised to ascertain and evaluate possible causative mutations for HI in the gene ABCA12. The identification of novel and known, point and complex mutations give molecular diagnostics a greater reservoir to help identify possible causative mutations in future cases. The spectrum of ABCA12 mutations, which have been attributed to different diseases within ARCI, was discussed. A HI immortalised cell line was derived from a patient with a compound heterozygote mutation in ABCA12, with a nonsense p.Glu2264X and c.5382-2a/g, a complex splice site mutation of the putative acceptor site (AG) preceding exon 35. Further investigations assessed the use of low affinity acceptor sites by the spliceosome. Immunohistochemistry of the patient biopsy showed an absence of ABCA12 and a reduction of ABCA1 proteins. Knockdown of ABCA12 in control K17 immortalised keratinocytes decreased expression levels of ABCA1 and LXRβ proteins. Functional studies of the HI patient derived cell line validated a HI cellular phenotype in monolayer. The expression levels of involucrin, TGM1 and K10 proteins showed how the patient derived HI cell line under calcium shift initiated premature terminal differentiation in vitro, compared to controls. The activation of nuclear hormone receptors PPARβ/δ and LXRβ by the application of their agonists on the HI cell line increased the transcript and protein levels of the reduced ABCA1. The same agonists reduced specific markers of differentiation, which were activated prematurely in the HI cell line under calcium shift, suggesting a potential therapeutic strategy to explore.

Subjects/Keywords: Harlequin Ichthyosis; autosomal recessive congenital ichthyosis; ABCA12

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APA (6^th Edition):

Bland, P. J. (2016). The genetic and functional role of ABCA12 in Harlequin Ichthyosis. (Doctoral Dissertation). Queen Mary, University of London. Retrieved from http://qmro.qmul.ac.uk/xmlui/handle/123456789/12571 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.775189

Chicago Manual of Style (16^th Edition):

Bland, Philip James. “The genetic and functional role of ABCA12 in Harlequin Ichthyosis.” 2016. Doctoral Dissertation, Queen Mary, University of London. Accessed March 08, 2021. http://qmro.qmul.ac.uk/xmlui/handle/123456789/12571 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.775189.

MLA Handbook (7^th Edition):

Bland, Philip James. “The genetic and functional role of ABCA12 in Harlequin Ichthyosis.” 2016. Web. 08 Mar 2021.

Vancouver:

Bland PJ. The genetic and functional role of ABCA12 in Harlequin Ichthyosis. [Internet] [Doctoral dissertation]. Queen Mary, University of London; 2016. [cited 2021 Mar 08]. Available from: http://qmro.qmul.ac.uk/xmlui/handle/123456789/12571 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.775189.

Council of Science Editors:

Bland PJ. The genetic and functional role of ABCA12 in Harlequin Ichthyosis. [Doctoral Dissertation]. Queen Mary, University of London; 2016. Available from: http://qmro.qmul.ac.uk/xmlui/handle/123456789/12571 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.775189

University of the Western Cape

3. Magwebu, Zandisiwe Emilia Z.E. Molecular genetics: strategies to identify congenital cataract genes in captive-bred vervet monkeys .

Degree: 2013, University of the Western Cape

URL: http://hdl.handle.net/11394/4265

► Molecular genetics: strategies to indentify congenital cataract genes in captive-bred Vervet monkeys Zandisiwe Emilia Magwebu MSc thesis, Department of Medical Biosciences, University of the Western… (more)

▼ Molecular genetics: strategies to indentify congenital cataract genes in captive-bred Vervet monkeys Zandisiwe Emilia Magwebu MSc thesis, Department of Medical Biosciences, University of the Western Cape The present study describes molecular aspects of inherited congenital cataract in captive-bred Vervet monkeys. Congenital cataracts are lens opacities that are present at birth or soon after birth and include hereditary cataracts or cataracts caused by infectious agents. The MRC Primate Unit is housing a colony of captive-bred Vervet monkeys in which 7.5% is suffering from congenital cataract. However, the parents of the affected individuals were asymptomatic. Six families within the colony have been identified to be affected by two types of morphologies (Ysutural and total cataract). Based on the evidence provided above, it was speculated that the colony was affected with autosomal recessive cataract. The main aim of this study was to facilitate a strategy for managing breeding programs by minimizing cataract occurrences in captive-bred Vervet monkeys. Integrated combination of clinical, molecular and bioinformatic strategies were used to identify and assess reciprocal candidate susceptibility genes for cataracts. The genes that are known to be responsible for most human congenital cataract cases were prioritized. The genes include Heat shock transcription factor 4 (HSF4), Crystalline Alpha A (CRYAA), glucosaminyl (N-acetyl) transferase 2 (GCNT2) and Lens intrinsic membrane protein 2 (LIM2). Twenty two subjects were selected based on their morphology (5 carriers, 5 controls and 12 cataracts). 2ml of blood was collected for Deoxyribonucleic acid (DNA) extraction. Coding exons and flanking regions were screened by polymerase chain reaction (PCR) amplification and sequenced. The CLC DNA workbench was used for results analysis. The screening of four genes revealed 20 sequence variants which were not present in the control individuals. Sequencing of HSF4 revealed three mutations: R116R, L245>L and P421>L in exon 5, 10 and 14, respectively. The coding exons for CRYAA showed two sequence variants: S134W and K166N in exon 3. Twelve mutations were identified in exon one of all three GCNT2 transcripts (A, B and C). These mutations include: G212G, H256>H, M258>V, N275>N, V16>I, Y122>F, S15>S, S24>N, S38>S, I118>I, D194>D and Y373>Y which was found in exon three of all transcripts. There were no mutations in LIM2, however, three single nucleotide polymorphisms (SNPs) were identified in exon 2 (P66>P) and 3 (I118>T and A127>T). The above mutations were conserved when aligned with other species. The sequence variations vary among the families and those individuals with the same or different cataract phenotype. Based on these findings, it can be concluded that the four candidate genes harbour mutations that are responsible for both phenotypes. The effect of these mutations in Vervet monkeys is not yet understood, however, their impact will be further investigated. For future studies, it will be of… Advisors/Committee Members: Seier, Jurgen (advisor).

Subjects/Keywords: Vervet monkeys; Congenital cataract; Autosomal recessive cataract

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APA (6^th Edition):

Magwebu, Z. E. Z. E. (2013). Molecular genetics: strategies to identify congenital cataract genes in captive-bred vervet monkeys . (Thesis). University of the Western Cape. Retrieved from http://hdl.handle.net/11394/4265

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Magwebu, Zandisiwe Emilia Z E. “Molecular genetics: strategies to identify congenital cataract genes in captive-bred vervet monkeys .” 2013. Thesis, University of the Western Cape. Accessed March 08, 2021. http://hdl.handle.net/11394/4265.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Magwebu, Zandisiwe Emilia Z E. “Molecular genetics: strategies to identify congenital cataract genes in captive-bred vervet monkeys .” 2013. Web. 08 Mar 2021.

Vancouver:

Magwebu ZEZE. Molecular genetics: strategies to identify congenital cataract genes in captive-bred vervet monkeys . [Internet] [Thesis]. University of the Western Cape; 2013. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/11394/4265.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Magwebu ZEZE. Molecular genetics: strategies to identify congenital cataract genes in captive-bred vervet monkeys . [Thesis]. University of the Western Cape; 2013. Available from: http://hdl.handle.net/11394/4265

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

4. Zhao, Yang. Mutation analysis of the USH2A gene in Japanese patients with non-syndromic autosomal recessive retinitis pigmentosa : 非症候群性の常染色体劣性網膜色素変性の日本人患者におけるUSH2A遺伝子の変異解析.

Degree: 博士（医学）, 2013, Hamamatsu University School of Medicine / 浜松医科大学

URL: http://hdl.handle.net/10271/2768

►

Objective: To identify disease-causing USH2A (Usher syndrome 2A) gene mutations in Japanese patients with non-syndromic retinitis pigmentosa (RP). Design: Case series.Participants: Hundred unrelated Japanese patients… (more)

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Objective: To identify disease-causing USH2A (Usher syndrome 2A) gene mutations in Japanese patients with non-syndromic retinitis pigmentosa (RP). Design: Case series.Participants: Hundred unrelated Japanese patients with no systemic manifestations of RP were identified, with the exclusion of families with obvious autosomal dominant inheritance. From these 100 patients, 18 RP patients with very likely pathogenic EYS (eyes shut homolog) gene mutations were excluded; finally, 82 patients were included in the study. The ophthalmological data of previously reported 13 unrelated Japanese patients with Usher syndrome (USH) by USH2A mutations were also collected.Methods: To determine the prevalence of USH2A gene mutations, all 72 exons were screened for mutations by polymerase chain reaction amplification. The phenotype analysis was based on ophthalmic examination and audiograms.Main Outcome Measures: DNA sequence variants, visual acuity, visual field assessments using Goldmann kinetic perimetry, optical coherence tomography images, and audiograms.Results: Mutation analysis of the USH2A gene revealed 5 very likely pathogenic mutations in 4 patients, 1 of whom did not have another possible pathogenic mutation. These very likely pathogenic mutations consisted of a deletion mutation, 2 splicing mutations, and 2 missense mutations. In addition, we also identified 3 possible pathogenic mutations in 3 individual patients. All the 4 patients with 1 or 2 very likely pathogenic mutations and 13 USH patients with USH2A mutations exhibited typical clinical features of RP, with the central visual acuity preserved relatively well up to their thirties.Conclusions: The spectrum of USH2A gene mutations among Japanese non-syndromic RP patients largely differs from that among European or North American population. Considering only 1 or 2 deleterious mutations, the observed prevalence of distinct USH2A gene mutations among Japanese arRP patients is 4% (4/100).

浜松医科大学学位論文医博第660号（平成25年9月20日）

Subjects/Keywords: Retinitis pigmentosa; autosomal recessive; USH2A gene; Japanese patient

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APA (6^th Edition):

Zhao, Y. (2013). Mutation analysis of the USH2A gene in Japanese patients with non-syndromic autosomal recessive retinitis pigmentosa : 非症候群性の常染色体劣性網膜色素変性の日本人患者におけるUSH2A遺伝子の変異解析. (Thesis). Hamamatsu University School of Medicine / 浜松医科大学. Retrieved from http://hdl.handle.net/10271/2768

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Zhao, Yang. “Mutation analysis of the USH2A gene in Japanese patients with non-syndromic autosomal recessive retinitis pigmentosa : 非症候群性の常染色体劣性網膜色素変性の日本人患者におけるUSH2A遺伝子の変異解析.” 2013. Thesis, Hamamatsu University School of Medicine / 浜松医科大学. Accessed March 08, 2021. http://hdl.handle.net/10271/2768.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Zhao, Yang. “Mutation analysis of the USH2A gene in Japanese patients with non-syndromic autosomal recessive retinitis pigmentosa : 非症候群性の常染色体劣性網膜色素変性の日本人患者におけるUSH2A遺伝子の変異解析.” 2013. Web. 08 Mar 2021.

Vancouver:

Zhao Y. Mutation analysis of the USH2A gene in Japanese patients with non-syndromic autosomal recessive retinitis pigmentosa : 非症候群性の常染色体劣性網膜色素変性の日本人患者におけるUSH2A遺伝子の変異解析. [Internet] [Thesis]. Hamamatsu University School of Medicine / 浜松医科大学; 2013. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/10271/2768.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Zhao Y. Mutation analysis of the USH2A gene in Japanese patients with non-syndromic autosomal recessive retinitis pigmentosa : 非症候群性の常染色体劣性網膜色素変性の日本人患者におけるUSH2A遺伝子の変異解析. [Thesis]. Hamamatsu University School of Medicine / 浜松医科大学; 2013. Available from: http://hdl.handle.net/10271/2768

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Vanderbilt University

5. Wanga, Valentine Adhiambo. Residual-based Test of Conditional Association between Continuous and Ordinal Variables with Application to Genome-wide Association Studies.

Degree: MS, Biostatistics, 2014, Vanderbilt University

URL: http://hdl.handle.net/1803/12859

► The discovery of genes linked with a large array of diseases has been accelerated by genome-wide association studies (GWAS), in which genetic variants in different… (more)

Subjects/Keywords: categorical.; additive; recessive; tenofovir; HIV; pharmacokinetics; creatinine clearance; CoCoBOT; dominant

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APA (6^th Edition):

Wanga, V. A. (2014). Residual-based Test of Conditional Association between Continuous and Ordinal Variables with Application to Genome-wide Association Studies. (Thesis). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/12859

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Wanga, Valentine Adhiambo. “Residual-based Test of Conditional Association between Continuous and Ordinal Variables with Application to Genome-wide Association Studies.” 2014. Thesis, Vanderbilt University. Accessed March 08, 2021. http://hdl.handle.net/1803/12859.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Wanga, Valentine Adhiambo. “Residual-based Test of Conditional Association between Continuous and Ordinal Variables with Application to Genome-wide Association Studies.” 2014. Web. 08 Mar 2021.

Vancouver:

Wanga VA. Residual-based Test of Conditional Association between Continuous and Ordinal Variables with Application to Genome-wide Association Studies. [Internet] [Thesis]. Vanderbilt University; 2014. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/1803/12859.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Wanga VA. Residual-based Test of Conditional Association between Continuous and Ordinal Variables with Application to Genome-wide Association Studies. [Thesis]. Vanderbilt University; 2014. Available from: http://hdl.handle.net/1803/12859

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Harvard University

6. Lim, Teng Ting. Exploring the genetic landscape of complex diseases using the recessive model.

Degree: PhD, Biology: Medical Sciences, Division of, 2014, Harvard University

URL: http://nrs.harvard.edu/urn-3:HUL.InstRepos:12274464

► High-throughput sequencing technologies have changed the way we identify, study and understand the role of rare variation in Mendelian diseases. Sequencing in complex diseases have… (more)

Subjects/Keywords: Genetics; complex disease; exome sequencing; rare variant; recessive

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APA (6^th Edition):

Lim, T. T. (2014). Exploring the genetic landscape of complex diseases using the recessive model. (Doctoral Dissertation). Harvard University. Retrieved from http://nrs.harvard.edu/urn-3:HUL.InstRepos:12274464

Chicago Manual of Style (16^th Edition):

Lim, Teng Ting. “Exploring the genetic landscape of complex diseases using the recessive model.” 2014. Doctoral Dissertation, Harvard University. Accessed March 08, 2021. http://nrs.harvard.edu/urn-3:HUL.InstRepos:12274464.

MLA Handbook (7^th Edition):

Lim, Teng Ting. “Exploring the genetic landscape of complex diseases using the recessive model.” 2014. Web. 08 Mar 2021.

Vancouver:

Lim TT. Exploring the genetic landscape of complex diseases using the recessive model. [Internet] [Doctoral dissertation]. Harvard University; 2014. [cited 2021 Mar 08]. Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:12274464.

Council of Science Editors:

Lim TT. Exploring the genetic landscape of complex diseases using the recessive model. [Doctoral Dissertation]. Harvard University; 2014. Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:12274464

7. Takeda, Ikuko. Autosomal recessive Andersen-Tawil syndrome with a novel mutation L94P in Kir2.1 : Kir2.1に新規ミスセンス変異（L94P）を認める常染色体劣性遺伝形式のAndersen-Tawil症候群.

Degree: 博士(医学), 2014, Hiroshima University / 広島大学

URL: http://ir.lib.hiroshima-u.ac.jp/00036281

► Aim: Dominant negative mutations of the inwardly rectifying K+ channel Kir2.1 cause Andersen-Tawil syndrome, an autosomal dominant disorder. Here, we identified a novel Kir2.1 mutation… (more)

Subjects/Keywords: Andersen-Tawil syndrome; KCNJ2; Kir2.1; autosomal recessive; patch clamp

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Takeda, I. (2014). Autosomal recessive Andersen-Tawil syndrome with a novel mutation L94P in Kir2.1 : Kir2.1に新規ミスセンス変異（L94P）を認める常染色体劣性遺伝形式のAndersen-Tawil症候群. (Thesis). Hiroshima University / 広島大学. Retrieved from http://ir.lib.hiroshima-u.ac.jp/00036281

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Takeda, Ikuko. “Autosomal recessive Andersen-Tawil syndrome with a novel mutation L94P in Kir2.1 : Kir2.1に新規ミスセンス変異（L94P）を認める常染色体劣性遺伝形式のAndersen-Tawil症候群.” 2014. Thesis, Hiroshima University / 広島大学. Accessed March 08, 2021. http://ir.lib.hiroshima-u.ac.jp/00036281.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Takeda, Ikuko. “Autosomal recessive Andersen-Tawil syndrome with a novel mutation L94P in Kir2.1 : Kir2.1に新規ミスセンス変異（L94P）を認める常染色体劣性遺伝形式のAndersen-Tawil症候群.” 2014. Web. 08 Mar 2021.

Vancouver:

Takeda I. Autosomal recessive Andersen-Tawil syndrome with a novel mutation L94P in Kir2.1 : Kir2.1に新規ミスセンス変異（L94P）を認める常染色体劣性遺伝形式のAndersen-Tawil症候群. [Internet] [Thesis]. Hiroshima University / 広島大学; 2014. [cited 2021 Mar 08]. Available from: http://ir.lib.hiroshima-u.ac.jp/00036281.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Takeda I. Autosomal recessive Andersen-Tawil syndrome with a novel mutation L94P in Kir2.1 : Kir2.1に新規ミスセンス変異（L94P）を認める常染色体劣性遺伝形式のAndersen-Tawil症候群. [Thesis]. Hiroshima University / 広島大学; 2014. Available from: http://ir.lib.hiroshima-u.ac.jp/00036281

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Debrecen

8. Rizvi, Danial. Pharmacological Management of Cystic Fibrosis .

Degree: DE – Általános Orvostudományi Kar, University of Debrecen

URL: http://hdl.handle.net/2437/273747

► Cystic fibrosis (CF) is an autosomal recessive defect occurring in approximately one in 3,500 live births based on data from neonatal screening. CF is clinically… (more)

Subjects/Keywords: Cystic Fibrosis; CFTR; Autosomal Recessive

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APA (6^th Edition):

Rizvi, D. (n.d.). Pharmacological Management of Cystic Fibrosis . (Thesis). University of Debrecen. Retrieved from http://hdl.handle.net/2437/273747

Note: this citation may be lacking information needed for this citation format:
No year of publication.
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Rizvi, Danial. “Pharmacological Management of Cystic Fibrosis .” Thesis, University of Debrecen. Accessed March 08, 2021. http://hdl.handle.net/2437/273747.

Note: this citation may be lacking information needed for this citation format:
No year of publication.
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Rizvi, Danial. “Pharmacological Management of Cystic Fibrosis .” Web. 08 Mar 2021.

Note: this citation may be lacking information needed for this citation format:
No year of publication.

Vancouver:

Rizvi D. Pharmacological Management of Cystic Fibrosis . [Internet] [Thesis]. University of Debrecen; [cited 2021 Mar 08]. Available from: http://hdl.handle.net/2437/273747.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
No year of publication.

Council of Science Editors:

Rizvi D. Pharmacological Management of Cystic Fibrosis . [Thesis]. University of Debrecen; Available from: http://hdl.handle.net/2437/273747

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
No year of publication.

University of New South Wales

9. Pan, Annie Ying-Hui. Disease gene identification in Australian kelpies.

Degree: Biotechnology & Biomolecular Sciences, 2012, University of New South Wales

URL: http://handle.unsw.edu.au/1959.4/51889 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:10558/SOURCE02?view=true

► The Australian Kelpie was generated from three pairs of working Scottish Collie dogs in 1870. The new breed was developed in an effort to ease… (more)

▼ The Australian Kelpie was generated from three pairs of working Scottish Collie dogs in 1870. The new breed was developed in an effort to ease the growing working demand faced by sheep farming. Like most dog breeds, inbreeding has been common within the Kelpie breed and persistent breeding of champion dogs (popular sire effect) has resulted in the spread of autosomal recessive conditions. One of these, Cerebellar Abiotrophy (CA) results in ataxia, characterized by a head tremor, poor body coordination and high stepping gait. Whole genome association and homozygosity analysis have mapped the CA locus to a 5 Mb region on chromosome 3 and identified a common SNP haplotype shared between all affecteds and some unaffected controls. This region was sequenced on a 454 platform in two affected and one control dogs. A total of 2019 differences were identified homozygous in the two affecteds compared to the control, 17 of which were synonymous substitutions in coding exons and substitutions in the untranslated regions of mRNA. On top of this, a total of 22 differences in introns and intergenic regions with high sequence conservation between other mammals and dogs were identified and investigated as possible causative mutations for CA in Kelpies. PCR and Sanger sequencing were employed to fill in 454 sequencing gaps for a total of 40 coding, non-coding exons and upstream regions of different genes within the candidate region. One intergenic (31674050) deletion conserved between other mammals and dogs was homozygous in the affecteds compared to controls and was predicted to disrupt a HSF2 transcription factor binding site for regulation of neighbouring genes. In addition, sequencing of the DMGDH gene in affected and unaffected control dogs identified a 223 bp insertion upstream of the last exon. This insertion may produce aberrant mRNA splicing and protein truncation, and may be a causative factor in the CA phenotype. Advisors/Committee Members: Wilton, Alan, Biotechnology & Biomolecular Sciences, Faculty of Science, UNSW, Delaney, Sven, Biotechnology & Biomolecular Sciences, Faculty of Science, UNSW.

Subjects/Keywords: Ataxia; Australian Kelpie; Cerebellar Abiotrophy; Dog; Canine model; Autosomal recessive disease

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Pan, A. Y. (2012). Disease gene identification in Australian kelpies. (Masters Thesis). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/51889 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:10558/SOURCE02?view=true

Chicago Manual of Style (16^th Edition):

Pan, Annie Ying-Hui. “Disease gene identification in Australian kelpies.” 2012. Masters Thesis, University of New South Wales. Accessed March 08, 2021. http://handle.unsw.edu.au/1959.4/51889 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:10558/SOURCE02?view=true.

MLA Handbook (7^th Edition):

Pan, Annie Ying-Hui. “Disease gene identification in Australian kelpies.” 2012. Web. 08 Mar 2021.

Vancouver:

Pan AY. Disease gene identification in Australian kelpies. [Internet] [Masters thesis]. University of New South Wales; 2012. [cited 2021 Mar 08]. Available from: http://handle.unsw.edu.au/1959.4/51889 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:10558/SOURCE02?view=true.

Council of Science Editors:

Pan AY. Disease gene identification in Australian kelpies. [Masters Thesis]. University of New South Wales; 2012. Available from: http://handle.unsw.edu.au/1959.4/51889 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:10558/SOURCE02?view=true

Texas A&M University

10. Lin, Shuxian. Dmp1 Regulates Osteocyte Function Via Wnt/β-Catenin Signaling Pathway.

Degree: PhD, Biomedical Sciences, 2014, Texas A&M University

URL: http://hdl.handle.net/1969.1/152604

► DMP1, dentin matrix protein 1, was cloned from a rat dentin cDNA library 20 years ago. Initially, this non-collagenous matrix protein was thought to be… (more)

▼ DMP1, dentin matrix protein 1, was cloned from a rat dentin cDNA library 20 years ago. Initially, this non-collagenous matrix protein was thought to be dentin specific and gained little interest in other scientific communities except the dental research area. Research that identified DMP1 mutations in humans and deletion in mice lead to the discovery of a novel disease: autosomal recessive hypophosphatemic rickets (ARHR). Functional studies reveal that DMP1 is essential for the maturation and functions of osteoblast and osteocyte via two possible mechanisms: 1) as a transcriptional factor that directly regulates osteo-/odonto-specific genes; and 2) as an extracellular matrix (ECM) protein, which controls bone and dentin mineralization. However, both theories appear controversy. Besides, the mechanism by which ARHR patients or Dmp1- null mice develop osteomalacia is largely unknown. In this study, we initially targeted DMP1 either in the nucleus only by replacing the endogenous signal peptide with the NLS signal peptide (named ^(NLS)DMP1), or targeted it in the ECM by using its own signal secretive peptide with the same recombinant DMP1 protein (named ^(SP)DMP1). The ^(NLS)DMP1 transgene, when expressed in the Dmp1-null osteoblast and osteocyte in vivo, failed to rescue the Dmp1-null phenotype, whereas the ^(SP)DMP1 transgene fully rescued the skeletal abnormalities of Dmp1-null mice, indicating that DMP1 functions as an ECM protein in vivo. In a separate research, we revealed an elevated β-catenin expression level in Dmp1-KO osteocytes, besides, the targeted expression of β-catenin in the osteocyte recaptured the osteomalacia phenotype, similar to that in Dmp1-KO mice. Furthermore, the targeted expression of DKK1 (a potent inhibitor of Wnt/β-catenin) in Dmp1-KO osteoblasts by crossing Dmp1-KO and 2.3 Col 1-Dkk1 mice, resulting in consequent blockade of Wnt/β-catenin signaling, significantly improved the rachitic/osteomalacic phenotype. The results of this study will expand our understanding of how the osteocytes regulate bone development and mineralization during the early postnatal period. In addition, this study has clinical relevance, as a high Pi diet alone fails to fully restore the osteomalacic status in patients, and normalizing the Wnt/β-catenin signaling may benefit these patients. Advisors/Committee Members: Feng, Jian Q. (advisor), Svoboda, Kathy (committee member), Dechow, Paul (committee member), Qin, Chunlin (committee member), Wang, Fen (committee member).

Subjects/Keywords: Dentin Matrix Protein 1; Wnt/β-catenin; Autosomal Recessive Hypophosphatemic Rickets; Skeleton; Tooth

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Lin, S. (2014). Dmp1 Regulates Osteocyte Function Via Wnt/β-Catenin Signaling Pathway. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/152604

Chicago Manual of Style (16^th Edition):

Lin, Shuxian. “Dmp1 Regulates Osteocyte Function Via Wnt/β-Catenin Signaling Pathway.” 2014. Doctoral Dissertation, Texas A&M University. Accessed March 08, 2021. http://hdl.handle.net/1969.1/152604.

MLA Handbook (7^th Edition):

Lin, Shuxian. “Dmp1 Regulates Osteocyte Function Via Wnt/β-Catenin Signaling Pathway.” 2014. Web. 08 Mar 2021.

Vancouver:

Lin S. Dmp1 Regulates Osteocyte Function Via Wnt/β-Catenin Signaling Pathway. [Internet] [Doctoral dissertation]. Texas A&M University; 2014. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/1969.1/152604.

Council of Science Editors:

Lin S. Dmp1 Regulates Osteocyte Function Via Wnt/β-Catenin Signaling Pathway. [Doctoral Dissertation]. Texas A&M University; 2014. Available from: http://hdl.handle.net/1969.1/152604

11. Gancheva, Diana / Ганчева, Диана. Peculiarities in the clinical approach in patients with Wilson’s disease. // Особености в клиничния подход при пациенти с болест на Wilson.

Degree: 2014, Medical University of Varna

URL: http://repository.mu-varna.bg/handle/nls/43

► [EN] The dissertation is dedicated to Wilson’s disease (WD) – a rare inherited autosomal recessive disease, related to a disorder of copper metabolism. Its aim… (more)

▼ [EN] The dissertation is dedicated to Wilson’s disease (WD) – a rare inherited autosomal recessive disease, related to a disorder of copper metabolism. Its aim is to optimize the diagnostic and therapeutic approach to this disease. The purpose of the thesis is to define the peculiarities of the clinical characteristics, the diagnostic possibilities, the course and follow-up of patients with WD. Seven tasks are placed. Sixty five persons with WD and two control groups comprising a total of 51 patients with other liver diseases are examined. Patients in specific clinical situations, with comorbidities and special therapeutic response are described. The estimated prevalence of WD in Northeastern Bulgaria is 3.96/100000 inhabitants. The average delay of diagnosis is approximately 3 years. The level of serum ceruloplasmin is the main diagnostic parameter, but about 15% of WD patients have normal values. The stimulated 24-hour urine copper excretion is a useful and accurate diagnostic test. Our results support the high diagnostic significance of Leipzig scoring system as a reliable combination of criteria for definite diagnosis of WD. In difficult and unclear cases liver biopsy with Rhodanine staining is used to confirm the diagnosis, but a negative result does not exclude it. Kayser-Fleischer ring is found in 35.4% of patients and disappears in 47.8% of them. A properly guided D-penicillamine therapy is safe during pregnancy for both fetus and mother. An algorithm for diagnosis, treatment and follow-up of WD patients is proposed. A register of WD patients is created in the Clinic of gastroenterology at St. Marina University hospital of Varna. Seven applied scientific contributions are listed./////////////////////////////////// [BG] Дисертационният труд е посветен на болестта на Wilson (БУ) - рядко наследствено автозомно ре-цесивно заболяване, свързано с нарушение на метаболизма на медта. Насочен е към оптимизиране на диагностичния и терапевтичния подход към това заболяване. Цел на дисертационния труд е да се дефинират особеностите в клиничната характеристика, диагностичните възможности, протичането, лечението и наблюдението на пациентите с БУ. Поставени са 7 задачи. Изследвани са 65 лица с БУ и две контролни групи от общо 51 болни с други чернодробни заболявания. Описани са пациенти в специфични клинични ситуации, със съпътстващи заболявания и особености в терапевтичния отговор. Установена е честота 3,96/100000 за населението на Североизточна България. Регистрирано е средно забавяне с 3 години в поставяне на диагнозата. Серумният церулоплазмин е основен диагностичен параметър, но около 15% от пациентите са с нормални равнища. Провокираната куприурия е полезен и точен диагностичен показател. Нашите резултати са в подкрепа на високата диагностична значимост на Лайпцигската точкова система като надеждна комбинация от критерии за сигурна диагноза. Морфологичното изследване с оцветяване с Rhodanine се използва в трудни и неясни случаи за потвърждение на диагнозата, но отрицателният резултат не я отхвърля. Пръстенът на…

Subjects/Keywords: Wilson’s disease; inherited autosomal recessive disease; copper metabolism; Вътрешни болести / Internal Diseases; Гастроентерология / Gastroenterology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Gancheva, Diana / Ганчева, �. (2014). Peculiarities in the clinical approach in patients with Wilson’s disease. // Особености в клиничния подход при пациенти с болест на Wilson. (Thesis). Medical University of Varna. Retrieved from http://repository.mu-varna.bg/handle/nls/43

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Gancheva, Diana / Ганчева, Диана. “Peculiarities in the clinical approach in patients with Wilson’s disease. // Особености в клиничния подход при пациенти с болест на Wilson.” 2014. Thesis, Medical University of Varna. Accessed March 08, 2021. http://repository.mu-varna.bg/handle/nls/43.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Gancheva, Diana / Ганчева, Диана. “Peculiarities in the clinical approach in patients with Wilson’s disease. // Особености в клиничния подход при пациенти с болест на Wilson.” 2014. Web. 08 Mar 2021.

Vancouver:

Gancheva, Diana / Ганчева �. Peculiarities in the clinical approach in patients with Wilson’s disease. // Особености в клиничния подход при пациенти с болест на Wilson. [Internet] [Thesis]. Medical University of Varna; 2014. [cited 2021 Mar 08]. Available from: http://repository.mu-varna.bg/handle/nls/43.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Gancheva, Diana / Ганчева �. Peculiarities in the clinical approach in patients with Wilson’s disease. // Особености в клиничния подход при пациенти с болест на Wilson. [Thesis]. Medical University of Varna; 2014. Available from: http://repository.mu-varna.bg/handle/nls/43

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Freie Universität Berlin

12. Abbasi Moheb, Lia. Identifizierung von drei neuen Genen für autosomal rezessive geistige Behinderung und molekulare Charakterisierung der zugrundeliegenden Gendefekte.

Degree: 2012, Freie Universität Berlin

URL: https://refubium.fu-berlin.de/handle/fub188/11246

► Mentale Retardierung (MR), eine der komplexesten Erkrankungen, hat eine weltweite Prävalenz von etwa 2% und ist ein häufiger Grund schwerster Behinderung. Aus diesem Grund ist… (more)

▼ Mentale Retardierung (MR), eine der komplexesten Erkrankungen, hat eine weltweite Prävalenz von etwa 2% und ist ein häufiger Grund schwerster Behinderung. Aus diesem Grund ist diese Erkrankung sowohl für die Familie als auch für die Gesellschaft eine enorme Belastung. Es hat sich gezeigt, dass genetische Defekte auf dem X-Chromosom nur für 10% aller Fälle von MR verantwortlich sind, daher muss die überwältigende Mehrheit der genetischen Defekte auf den Autosomen kodiert sein. Die Erforschung der autosomalen MR hat bislang jedoch wesentlich weniger Aufmerksamkeit erhalten. Die Strategie zur Identifizierung der an autosomal rezessiven Erbkrankheiten beteiligten Gene umfasst, Homozygosity Mapping, in großen blutsverwandten Familien mit anschließendem Sequenzieren der Kandidatengene um Mutationen aufzuspüren. In westlichen Gesellschaften, wo ein Großteil der Erforschung von MR stattfindet, ist diese Strategie aufgrund von kleinen Familien und seltener Blutsverwandtschaft der Eltern kaum einsetzbar. Um die molekularen Ursachen autosomal rezessiver MR (ARMR) systematisch zu entschlüsseln, um als Grundvoraussetzung für Diagnose, Beratung und Therapie zu dienen, haben wir den Fokus auf große, blutsverwandte iranische Familien gelegt. In unseren Forschungen zu den molekularen Ursachen von ARMR haben wir neue ARMR-Loci identifiziert, doch sind darunter sechs Hot Spot-Loci für unspezifische oder nicht syndromaleARMR(NS-ARMR). Daraus kann geschlossen werden, dass zumindest in der iranischen Bevölkerung nicht alle Gendefekte selten sind und dass die Möglichkeit gemeinsamer molekularer Ursachen von NS-ARMR nicht ausgeschlossen werden kann. Diese Arbeit ist Teil des großen Projekts die molekularen Ursachen von ARMR zu erforschen. Zwei der sechs Hot Spots für ARMR wurden untersucht und die zugrunde liegenden Gendefekte identifiziert. Die Kopplungsintervalle von zwei iranischen Familien mit mehreren von NS-ARMR betroffenen Patienten überlappen auf Chr19q13.2-q13.31. Im Gen ZNF526 wurden zwei Missense-Mutationen mit hoher Pathogenitätsvoraussage identifiziert. ZNF526 kodiert ein Krüppel-Zinkfinger-Protein. Eine dieser Mutationen wurde in einer weiteren Familie mit NS-ARMR identifiziert, die in der gleichen Stadt im Nordwesten des Irans wohnt. Weitere Analysen ergaben einen gemeinsamen Haplotyp beider Familien, die daher entfernt miteinander verwandt sein müssen. Beide Mutationen betreffen funktionelle Domänen von ZNF526. In silico- Proteinmodellierung zeigte eine Veränderung der Proteinkonformation, welche wahrscheinlich die Funktion des Proteins behindert. Eine Minderung der DNA- Affinität wurde anhand von Chip-seq bestätigt. Spezifische Veränderung des Genexpressionsmusters in Lymphoblasten der Patienten wurde anhand von Arrays gezeigt. Dieser Befund konnte in ZNF526-defizienten Neuroblastomzellen rekapituliert werden. Die Annotation der Genfunktionen zeigte eine Anreicherung der deregulierten Gene in Singal-und Stoffwechselwegen, die eine Rolle in der Proteinsynthese, mitochondrialer Dysfunktion, Energiemetabolismus und… Advisors/Committee Members: w (gender), Prof. Dr. H. H. Ropers (firstReferee), Prof. Dr. S. Sigrist (furtherReferee).

Subjects/Keywords: Intellectual Disability; autosomal recessive; brain; 500 Naturwissenschaften und Mathematik::570 Biowissenschaften; Biologie

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Abbasi Moheb, L. (2012). Identifizierung von drei neuen Genen für autosomal rezessive geistige Behinderung und molekulare Charakterisierung der zugrundeliegenden Gendefekte. (Thesis). Freie Universität Berlin. Retrieved from https://refubium.fu-berlin.de/handle/fub188/11246

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Abbasi Moheb, Lia. “Identifizierung von drei neuen Genen für autosomal rezessive geistige Behinderung und molekulare Charakterisierung der zugrundeliegenden Gendefekte.” 2012. Thesis, Freie Universität Berlin. Accessed March 08, 2021. https://refubium.fu-berlin.de/handle/fub188/11246.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Abbasi Moheb, Lia. “Identifizierung von drei neuen Genen für autosomal rezessive geistige Behinderung und molekulare Charakterisierung der zugrundeliegenden Gendefekte.” 2012. Web. 08 Mar 2021.

Vancouver:

Abbasi Moheb L. Identifizierung von drei neuen Genen für autosomal rezessive geistige Behinderung und molekulare Charakterisierung der zugrundeliegenden Gendefekte. [Internet] [Thesis]. Freie Universität Berlin; 2012. [cited 2021 Mar 08]. Available from: https://refubium.fu-berlin.de/handle/fub188/11246.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Abbasi Moheb L. Identifizierung von drei neuen Genen für autosomal rezessive geistige Behinderung und molekulare Charakterisierung der zugrundeliegenden Gendefekte. [Thesis]. Freie Universität Berlin; 2012. Available from: https://refubium.fu-berlin.de/handle/fub188/11246

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Queen Mary, University of London

13. Bradshaw, Teisha Y. The cellular phenotype of the neurodegenerative disease autosomal recessive spastic ataxia of Charlevoix-Saguenay.

Degree: PhD, 2014, Queen Mary, University of London

URL: http://qmro.qmul.ac.uk/xmlui/handle/123456789/8924 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.667309

► Autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS) is an early onset neurodegenerative disorder resulting from mutations in the SACS gene that encodes the protein… (more)

▼ Autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS) is an early onset neurodegenerative disorder resulting from mutations in the SACS gene that encodes the protein sacsin. Sacsin is a 520kDa multi-domain protein localised at the cytosolic face of the outer mitochondrial membrane with suggested roles in proteostasis and most recently in the regulation of mitochondrial morphology. An excessively interconnected mitochondrial network was observed as a consequence of reduced levels of sacsin protein following SACS knockdown in neuroblastoma cells as well as in an ARSACS patient carrying the common Quebec homozygous SACS mutation 8844delT. Moreover, it was suggested that sacsin has a role in mitochondrial fission as it was found to interact with mitochondrial fission protein Dynamin related protein 1 (Drp1). The aim of this thesis was to explore sacsin’s role in the regulation of mitochondrial morphology and dynamics in non-Quebec ARSACS patients and sacsin knockdown fibroblasts. This study shows that loss of sacsin function promotes a more interconnected mitochondrial network in non-Quebec ARSACS patients and in sacsin knockdown fibroblasts. Moreover, recruitment of the essential mitochondrial fission protein Drp1 to the mitochondria was significantly reduced in ARSACS patient cells and in sacsin knockdown fibroblasts. This reduced recruitment of Drp1 to mitochondria also occurred when cells were treated to induce mitochondrial fission. Furthermore, both the size and intensity of Drp1 foci localised to the mitochondria were significantly reduced in both sacsin knockdown and patient fibroblasts. Finally, reduced ATP production, decreased respiratory capacity of mitochondria and an increase in mitochondrial reactive oxygen species demonstrated impaired mitochondrial function in ARSACS patient and sacsin knockdown fibroblasts. These results suggest a role for sacsin in the stabilisation or recruitment of cytoplasmic Drp1 to prospective sites of mitochondrial fission similar to that observed by other mitochondrial fission accessory proteins.

Subjects/Keywords: 616.8; Medicine; Endocrinology; Autosomal recessive spastic ataxia of Charlevoix Saguenay; Neurodegenerative diseases; SACS gene; Sacsin

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Bradshaw, T. Y. (2014). The cellular phenotype of the neurodegenerative disease autosomal recessive spastic ataxia of Charlevoix-Saguenay. (Doctoral Dissertation). Queen Mary, University of London. Retrieved from http://qmro.qmul.ac.uk/xmlui/handle/123456789/8924 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.667309

Chicago Manual of Style (16^th Edition):

Bradshaw, Teisha Y. “The cellular phenotype of the neurodegenerative disease autosomal recessive spastic ataxia of Charlevoix-Saguenay.” 2014. Doctoral Dissertation, Queen Mary, University of London. Accessed March 08, 2021. http://qmro.qmul.ac.uk/xmlui/handle/123456789/8924 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.667309.

MLA Handbook (7^th Edition):

Bradshaw, Teisha Y. “The cellular phenotype of the neurodegenerative disease autosomal recessive spastic ataxia of Charlevoix-Saguenay.” 2014. Web. 08 Mar 2021.

Vancouver:

Bradshaw TY. The cellular phenotype of the neurodegenerative disease autosomal recessive spastic ataxia of Charlevoix-Saguenay. [Internet] [Doctoral dissertation]. Queen Mary, University of London; 2014. [cited 2021 Mar 08]. Available from: http://qmro.qmul.ac.uk/xmlui/handle/123456789/8924 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.667309.

Council of Science Editors:

Bradshaw TY. The cellular phenotype of the neurodegenerative disease autosomal recessive spastic ataxia of Charlevoix-Saguenay. [Doctoral Dissertation]. Queen Mary, University of London; 2014. Available from: http://qmro.qmul.ac.uk/xmlui/handle/123456789/8924 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.667309

University of Lund

14. Ellberg, Carolina. Insights into breast cancer: New familial patterns and identification of a potential predictive marker.

Degree: 2014, University of Lund

URL: https://lup.lub.lu.se/record/4393868 ; https://portal.research.lu.se/ws/files/4329456/4393898.pdf

► The last proportion of heredity in breast cancer has proven to be somewhat elusive despite massive attempts to identify the associated factors. Approximately 50 percent… (more)

▼ The last proportion of heredity in breast cancer has proven to be somewhat elusive despite massive attempts to identify the associated factors. Approximately 50 percent of breast cancer caused by familial factors is currently explained. The five-year survival for breast cancer patients is excellent; however, breast cancer is considered a chronic disease, and given enough time, new tumors can develop. Women age 40 and older are offered screening mammography. However, population screening is expensive, and being able to pinpoint those who are at high risk of breast cancer would be beneficial. Both genetic and environmental risk factors could be used to select women who need screening. A major aim of this thesis was to try to identify potential familial patterns as candidates for hereditary breast cancer. In Paper I, we studied horizontal family history of breast cancer in relation to histology to discover a candidate phenotype for recessive inheritance. A horizontal pedigree pattern is characterized by two or more sisters diagnosed with breast cancer, without a family history of breast cancer in prior generations. A horizontal inheritance was more common in patients with tubular carcinoma compared with other histologic subtypes. Therefore, we propose that breast cancer patients with tubular carcinoma who have a sister or sisters diagnosed with breast cancer are candidates for genetic studies when searching for a recessively inherited predisposing gene. In paper II, we studied the occurrence of cancer in first-degree relatives of breast cancer patients diagnosed with the lobular carcinoma histologic subtype compared with other histological subtypes of breast cancer. We found a hereditary pattern involving breast cancer patients with lobular carcinoma and having a father diagnosed with cancer. The association was independent of a family history of breast cancer in sisters, the mother and grandmothers. Similarly, even though prostate cancer was prominent in the fathers, the association remained after removal of fathers diagnosed with prostate cancer. In paper III, we confirmed a previously reported younger age at breast cancer diagnosis in carriers of a BRCA1 mutation of paternal origin compared with maternal origin. Additionally, we observed an older age at ovarian cancer diagnosis in carriers of a BRCA1 mutation of paternal origin compared with maternal origin. No such observations were observed for BRCA2 mutation carriers. In paper IV, we studied the occurrence of spider telangiectasias at the time of breast cancer diagnosis in relation to hormonal risk factors. We reported that the occurrence of spider telangiectasias was associated with several hormonal risk factors such as weight, parity, history of oral contraceptive use, and menopausal hormone therapy use. A better overall survival was observed in older breast cancer patients who displayed spider telangiectasias at the time of breast cancer diagnosis.

Subjects/Keywords: Cancer and Oncology; BRCA1; BRCA2; Spider telangiectasias; Heredity; Parental inheritance; Recessive; familial; Breast cancer

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APA (6^th Edition):

Ellberg, C. (2014). Insights into breast cancer: New familial patterns and identification of a potential predictive marker. (Doctoral Dissertation). University of Lund. Retrieved from https://lup.lub.lu.se/record/4393868 ; https://portal.research.lu.se/ws/files/4329456/4393898.pdf

Chicago Manual of Style (16^th Edition):

Ellberg, Carolina. “Insights into breast cancer: New familial patterns and identification of a potential predictive marker.” 2014. Doctoral Dissertation, University of Lund. Accessed March 08, 2021. https://lup.lub.lu.se/record/4393868 ; https://portal.research.lu.se/ws/files/4329456/4393898.pdf.

MLA Handbook (7^th Edition):

Ellberg, Carolina. “Insights into breast cancer: New familial patterns and identification of a potential predictive marker.” 2014. Web. 08 Mar 2021.

Vancouver:

Ellberg C. Insights into breast cancer: New familial patterns and identification of a potential predictive marker. [Internet] [Doctoral dissertation]. University of Lund; 2014. [cited 2021 Mar 08]. Available from: https://lup.lub.lu.se/record/4393868 ; https://portal.research.lu.se/ws/files/4329456/4393898.pdf.

Council of Science Editors:

Ellberg C. Insights into breast cancer: New familial patterns and identification of a potential predictive marker. [Doctoral Dissertation]. University of Lund; 2014. Available from: https://lup.lub.lu.se/record/4393868 ; https://portal.research.lu.se/ws/files/4329456/4393898.pdf

University of Edinburgh

15. McQuillan, Ruth. Homozygosity, inbreeding and health in European populations.

Degree: PhD, 2009, University of Edinburgh

URL: http://hdl.handle.net/1842/5946

► Inbreeding results in increased levels of homozygosity for deleterious recessive alleles, leading to increased incidence of monogenic disease in inbred families. It has also been… (more)

▼ Inbreeding results in increased levels of homozygosity for deleterious recessive alleles, leading to increased incidence of monogenic disease in inbred families. It has also been suggested that inbreeding increases the risk of diseases such as cancer and heart disease, implying a role for the combined effects of many recessive alleles distributed across the genome. A better understanding of the links between inbreeding, homozygosity and disease is therefore of interest to those concerned with understanding the genetic architecture of complex disease. A homozygous genotype is defined as autozygous if both alleles originate from the same ancestor. Quantifying inbreeding involves quantifying autozygosity. A new, observational method of quantifying autozygosity using genomic data is developed here. Based on runs of homozygosity (ROH), this approach has a sound theoretical basis in the biological processes involved in inbreeding. It is also backed by strong empirical evidence, correlating strongly with pedigree-derived estimates of inbreeding and discriminating well between populations with different demographic histories. ROH are a signature of autozygosity, but not necessarily autozygosity of recent origin. Short ROH are shown to be abundant in demonstrably outbred individuals and it is suggested that this is a source of individual genetic variation which merits investigation as a disease risk factor, although denser genotype scans than those used in the present study are required for the reliable detection of very short ROH. In the absence of such dense scans, it is suggested that ROH longer than 1 or 1.5 Mb be used to estimate the effects of inbreeding on disease or quantitative physiological traits (QT), and that a simple measure of homozygosity be used to investigate overall recessive effects. Evidence for recessive effects on 13 QT important in cardiovascular and metabolic disease was investigated in 5 European isolate populations, characterised by heightened levels of inbreeding. A significant decrease in height was associated both with increased homozygosity and (to a lesser extent) with increased ROH longer than 5 Mb (i.e. inbreeding) estimated using a 300,000 SNP panel. No evidence was found for recessive effects on any of the other QTs. Evidence for recessive effects on colorectal cancer risk were investigated in two outbred case control samples typed with a 500,000 SNP panel. Cases were significantly more homozygous and had more of their genome in short ROH than did controls. Cases were significantly more homozygous than controls even when inbred individuals were removed from the sample. There was also some evidence of an inbreeding effect, with inbred subjects having slightly significantly higher odds of colorectal cancer than outbred subjects. This study provides evidence of recessive effects on a common, complex disease in outbred populations and on height in both inbred and outbred populations and shows that such effects are not solely attributable to increased levels of homozygosity resulting from recent…

Subjects/Keywords: 576.58; homozygosity; inbreeding; consanguinity; recessive effects

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

McQuillan, R. (2009). Homozygosity, inbreeding and health in European populations. (Doctoral Dissertation). University of Edinburgh. Retrieved from http://hdl.handle.net/1842/5946

Chicago Manual of Style (16^th Edition):

McQuillan, Ruth. “Homozygosity, inbreeding and health in European populations.” 2009. Doctoral Dissertation, University of Edinburgh. Accessed March 08, 2021. http://hdl.handle.net/1842/5946.

MLA Handbook (7^th Edition):

McQuillan, Ruth. “Homozygosity, inbreeding and health in European populations.” 2009. Web. 08 Mar 2021.

Vancouver:

McQuillan R. Homozygosity, inbreeding and health in European populations. [Internet] [Doctoral dissertation]. University of Edinburgh; 2009. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/1842/5946.

Council of Science Editors:

McQuillan R. Homozygosity, inbreeding and health in European populations. [Doctoral Dissertation]. University of Edinburgh; 2009. Available from: http://hdl.handle.net/1842/5946

Queen Mary, University of London

16. Duncan, Emma Jane. The neurodegenerative disease Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS) : cellular defects due to loss of sacsin function.

Degree: PhD, 2016, Queen Mary, University of London

URL: http://qmro.qmul.ac.uk/xmlui/handle/123456789/23110 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.765788

► Sacsin, which is mutated in the neurodegenerative disease Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS), is a 520 kDa modular protein with regions of homology… (more)

▼ Sacsin, which is mutated in the neurodegenerative disease Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS), is a 520 kDa modular protein with regions of homology to molecular chaperones and domains linking to the ubiquitin proteasome system. This suggests a role in proteostasis. Previously, sacsin has been shown to partially localise with mitochondria, and loss of sacsin results in elongated and dysfunctional mitochondria. Moreover, alterations in neurofilaments have recently been reported in a mouse model of ARSACS. Despite these findings, pathophysiological mechanisms of ARSACS are poorly understood. The aim of this thesis was to elucidate the cellular role of sacsin by determining how loss of its function leads to the observed mitochondrial and intermediate filament defects. This hoped to shed light on the mechanism of disease in ARSACS. The results indicate that the mitochondrial elongation seen in ARSACS is likely due to reduced mitochondrial localisation of the essential fission factor DRP1. This may be mediated by loss of function of a complex involving sacsin and dynactin-6, a subunit of the dynein-dynactin motor complex, which has previously been shown to be required for DRP1 mitochondrial recruitment. DRP1-mediated mitochondrial fission is necessary for mitochondrial quality control; hence a disruption to mitochondrial quality control is likely to occur in sacsin deficient cells, which may explain the mitochondrial dysfunction in ARSACS. Furthermore, sacsin null cells display a dramatic collapse and perinuclear bundling of the vimentin intermediate filament network. This is coupled with the displacement of cellular organelles, particularly mitochondria, early endosomes and the Golgi, which accumulate at the periphery of the vimentin bundle. These are characteristic features of aggresome formation, indicating an aggregation of misfolded protein, which occurs due to disrupted proteostasis. Further supporting this, the proteostasis components ubiquitin, HSP70, LAMP2 and p62 are recruited to the perinuclear vimentin bundles. In summary, the findings of this thesis indicate a role for sacsin in mitochondrial and protein quality control, the dysfunction of which is likely to be particularly detrimental in neurons. Mitochondrial dysfunction along with protein misfolding and aggregation are implicated in many neurodegenerative diseases, and ARSACS is no exception.

Subjects/Keywords: 616.8; Endocrinology; Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay; ARSACS; Neurodegenerative Disease; Sacsin

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Duncan, E. J. (2016). The neurodegenerative disease Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS) : cellular defects due to loss of sacsin function. (Doctoral Dissertation). Queen Mary, University of London. Retrieved from http://qmro.qmul.ac.uk/xmlui/handle/123456789/23110 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.765788

Chicago Manual of Style (16^th Edition):

Duncan, Emma Jane. “The neurodegenerative disease Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS) : cellular defects due to loss of sacsin function.” 2016. Doctoral Dissertation, Queen Mary, University of London. Accessed March 08, 2021. http://qmro.qmul.ac.uk/xmlui/handle/123456789/23110 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.765788.

MLA Handbook (7^th Edition):

Duncan, Emma Jane. “The neurodegenerative disease Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS) : cellular defects due to loss of sacsin function.” 2016. Web. 08 Mar 2021.

Vancouver:

Duncan EJ. The neurodegenerative disease Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS) : cellular defects due to loss of sacsin function. [Internet] [Doctoral dissertation]. Queen Mary, University of London; 2016. [cited 2021 Mar 08]. Available from: http://qmro.qmul.ac.uk/xmlui/handle/123456789/23110 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.765788.

Council of Science Editors:

Duncan EJ. The neurodegenerative disease Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS) : cellular defects due to loss of sacsin function. [Doctoral Dissertation]. Queen Mary, University of London; 2016. Available from: http://qmro.qmul.ac.uk/xmlui/handle/123456789/23110 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.765788

Indian Institute of Science

17. Singhmar, Pooja. Functional Analysis Of Primary Microcephaly Gene Product ASPM.

Degree: PhD, Faculty of Science, 2013, Indian Institute of Science

URL: http://etd.iisc.ac.in/handle/2005/2060

► Autosomal recessive primary microcephaly (MCPH) is defined by congenital microcephaly and associated mental retardation with head circumference of the affected individual at least 3 standard… (more)

▼ Autosomal recessive primary microcephaly (MCPH) is defined by congenital microcephaly and associated mental retardation with head circumference of the affected individual at least 3 standard deviations below age- and sex-means. It is a disorder of abnormal fetal brain growth which is a consequence of impaired neurogenesis. It is genetically heterogeneous with seven known loci and genes for all the seven loci have been identified: MCPH-1-MCPH1, MCPH2-WDR62, MCPH3-CDK5RAP2, MCPH4-CEP152, MCPH5-ASPM, MCPH6-CENPJ, and MCPH7-STIL. All the seven MCPH proteins localize at the centrosome. Apart from MCPH, many other proteins associated with the phenotype microcephaly have been localized to the centrosome or linked to it functionally. For example, Microcephalic osteodysplastic primordial dwarfism type II protein PCNT and Seckel syndrome protein ATR are also centrosomal proteins. All of the above findings show the importance of centrosomal proteins as the key players in neurogenesis and brain development. However, the exact mechanism as to how the loss-of-function of these proteins leads to microcephaly remains to be elucidated. The study of MCPH genes can also provide insights into the basics of neurogenesis that lead to a normal brain size. The most common cause of MCPH is mutations in the ASPM (abnormal spindle-like, microcephaly-associated protein) gene. The main aim of this study was to gain insight into the function of ASPM using the yeast two-hybrid technique. The main findings of the study are listed below. To find novel interacting proteins for SPM, a GAL4 based yeast two-hybrid system was used. The 3,477 amino acid long ASPM was divided into eight different baits and each bait was individually used for screening a human fetal brain cDNA library cloned in the pACT2 vector. To generate baits, the different regions were amplified from human fetal brain cDNA and cloned in-frame with the GAL4-DNA binding domain in the pGBKT7 vector. Screening with a C-terminus ASPM bait (pGBKT7-CTR) identified Angelman syndrome protein ubiquitin protein ligase E3A (UBE3A) as an ASPM interactor. A region of UBE3A from amino acids 639-875 was found to interact with ASPM. The identification of UBE3A as an ASPM interacting partner was interesting as more than 80% of Angleman syndrome patients are reported to have microcephaly. Screening with the baits pGBKT7-1.4 kb ASPM and pGBKT7-2.1 kb ASPM harboring parts of IQ domain identified calmodulin as an ASPM interating partner. The full length calmodulin was found to interact with the IQ domain of ASPM. The interactions identified in the yeast two-hybrid assay were confirmed in vivo by co-immunoprecipitation studies. For this, a rabbit polyclonal anti-ASPM antibody was raised against the N-terminal region of ASPM (from amino acids 544-1059). The specificity of the antibody was tested by Western blot analysis and immunofluorescence microscopy. ASPM antibody recognized the 410 KDa fulllength ASPM protein in lysates from human fetal tissues and different cell lines.… Advisors/Committee Members: Arun Kumar, * (advisor).

Subjects/Keywords: Microcephaly Gene; Autosomal Recessive Primary Microcephaly (MCPH); Abnormal Spindle-like, Micrcephaly Associated Protein (ASPM); MCPH Genes; Microcephaly Protein; Neurology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Singhmar, P. (2013). Functional Analysis Of Primary Microcephaly Gene Product ASPM. (Doctoral Dissertation). Indian Institute of Science. Retrieved from http://etd.iisc.ac.in/handle/2005/2060

Chicago Manual of Style (16^th Edition):

Singhmar, Pooja. “Functional Analysis Of Primary Microcephaly Gene Product ASPM.” 2013. Doctoral Dissertation, Indian Institute of Science. Accessed March 08, 2021. http://etd.iisc.ac.in/handle/2005/2060.

MLA Handbook (7^th Edition):

Singhmar, Pooja. “Functional Analysis Of Primary Microcephaly Gene Product ASPM.” 2013. Web. 08 Mar 2021.

Vancouver:

Singhmar P. Functional Analysis Of Primary Microcephaly Gene Product ASPM. [Internet] [Doctoral dissertation]. Indian Institute of Science; 2013. [cited 2021 Mar 08]. Available from: http://etd.iisc.ac.in/handle/2005/2060.

Council of Science Editors:

Singhmar P. Functional Analysis Of Primary Microcephaly Gene Product ASPM. [Doctoral Dissertation]. Indian Institute of Science; 2013. Available from: http://etd.iisc.ac.in/handle/2005/2060

18. Carton-Buonafine, Coralie. Architecture génétique des troubles du spectre autistique dans les îles Féroé : Genetic Architecture of Autism Spectrum Disorders in the Faroe Islands.

Degree: Docteur es, Sciences de la vie et de la santé, 2018, Sorbonne Paris Cité

URL: http://www.theses.fr/2018USPCC117

► Les Troubles du Spectre Autistique (TSA) forment un groupe hétérogène de troubles neurodéveloppementaux caractérisés par des déficits de l’interaction sociale et de la communication ainsi… (more)

▼ Les Troubles du Spectre Autistique (TSA) forment un groupe hétérogène de troubles neurodéveloppementaux caractérisés par des déficits de l’interaction sociale et de la communication ainsi que la présence de comportements répétitifs et d’intérêts restreints. Les TSA affectent environ un individu sur 68. Ils se manifestent généralement durant les trois premières années de vie mais, pour certains cas, les symptômes sont reconnus plus tard, quand les exigences sociales augmentent. Les études de jumeaux et la récurrence des troubles dans certaines familles démontrent l’importance des facteurs génétiques dans la vulnérabilité aux TSA. Cependant, l’architecture génétique des TSA reste difficile à caractériser car elle est extrêmement hétérogène et il est très compliqué d’identifier, pour chacun des patients, la combinaison d’allèles à risque. Notre laboratoire a identifié la première voie génétique associée aux TSA – la voie NLGN-NRXN-SHANK- qui joue un rôle clé dans la plasticité synaptique. Il existe un nombre de plus en plus grand de gènes associés aux TSA mais peu d’études ont été réalisées sur des cohortes épidémiologiques et dans des populations isolées. L'analyse des données de génotypage et de séquençage d’exome de 357 individus issus des îles Féroé (36 patients, 136 apparentés des patients, 185 témoins) nous a permis de mettre en évidence un nombre plus important de Variations du Nombre de Copies (CNVs), un coefficient de consanguinité supérieur, un plus grand nombre de mutations homozygotes et délétères ainsi qu’un Polygenic Risk Score (ASD-PRS) supérieur chez les patients TSA comparés aux individus témoins. Notre analyse confirme le rôle de plusieurs loci associés aux TSA (NRXN1, ADNP, délétion 22q11) et a permis d’identifier de nouvelles mutations tronquant la protéine (GRIK2, ROBO1, NINL et IMMP2L) ou récessives (KIRREL3 et CNTNAP2) affectant des gènes déjà associés aux TSA. Nous avons également mis en évidence trois nouveaux gènes candidats jouant un rôle important dans la plasticité synaptique (RIMS4, KALRN et PLA2G4A) à travers la présence de mutations de novo délétères chez des patients sans déficience intellectuelle. Au total, nous avons pu identifier une cause génétique expliquant les TSA pour 11% des patients et au moins une mutation fortement délétère dans des gènes candidats chez 39% des patients. Aucune cause génétique n'a pu être trouvée chez 50% des patients. En résumé, notre étude permet de mieux comprendre l’architecture génétique des TSA dans les populations isolées en soulignant à la fois l'impact des variants communs et des variants rares mais également en révélant le rôle de nouveaux gènes pour les TSA. Ces gènes codent pour des protéines essentielles pour le neurodéveloppement et l’identification de ces facteurs impliqués dans la formation et l'entretien des synapses pourrait ainsi fournir de nouvelles pistes afin de mieux comprendre les bases biologiques des TSA et de découvrir de nouvelles stratégies thérapeutiques. Il est cependant nécessaire de comprendre plus avant l'impact de la… Advisors/Committee Members: Bourgeron, Thomas (thesis director).

Subjects/Keywords: Troubles du Spectre Autistique (TSA); Consanguinité; Mutations de novo; Mutations récessives; Autism Spectrum Disorders (ASD); Inbreeding; De novo variants; Recessive variants

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Carton-Buonafine, C. (2018). Architecture génétique des troubles du spectre autistique dans les îles Féroé : Genetic Architecture of Autism Spectrum Disorders in the Faroe Islands. (Doctoral Dissertation). Sorbonne Paris Cité. Retrieved from http://www.theses.fr/2018USPCC117

Chicago Manual of Style (16^th Edition):

Carton-Buonafine, Coralie. “Architecture génétique des troubles du spectre autistique dans les îles Féroé : Genetic Architecture of Autism Spectrum Disorders in the Faroe Islands.” 2018. Doctoral Dissertation, Sorbonne Paris Cité. Accessed March 08, 2021. http://www.theses.fr/2018USPCC117.

MLA Handbook (7^th Edition):

Carton-Buonafine, Coralie. “Architecture génétique des troubles du spectre autistique dans les îles Féroé : Genetic Architecture of Autism Spectrum Disorders in the Faroe Islands.” 2018. Web. 08 Mar 2021.

Vancouver:

Carton-Buonafine C. Architecture génétique des troubles du spectre autistique dans les îles Féroé : Genetic Architecture of Autism Spectrum Disorders in the Faroe Islands. [Internet] [Doctoral dissertation]. Sorbonne Paris Cité; 2018. [cited 2021 Mar 08]. Available from: http://www.theses.fr/2018USPCC117.

Council of Science Editors:

Carton-Buonafine C. Architecture génétique des troubles du spectre autistique dans les îles Féroé : Genetic Architecture of Autism Spectrum Disorders in the Faroe Islands. [Doctoral Dissertation]. Sorbonne Paris Cité; 2018. Available from: http://www.theses.fr/2018USPCC117

Université Montpellier II

19. Poulicard, Nils. Emergence et adaptation du Rice yellow mottle virus : relations entre histoire évolutive, contournement de résistance et interactions hôte/pathogène : Emergence and adaptation of Rice yellow mottle virus : relationships between evolutionary history, resistance-breakdown and host/pathogen interactions.

Degree: Docteur es, Biochimie et biologie moléculaire, 2010, Université Montpellier II

URL: http://www.theses.fr/2010MON20121

►

Le Rice yellow mottle virus (RYMV) est un virus émergeant qui constitue actuellement une contrainte majeure à la riziculture sur le continent africain. Quelques rares… (more)

▼

Le Rice yellow mottle virus (RYMV) est un virus émergeant qui constitue actuellement une contrainte majeure à la riziculture sur le continent africain. Quelques rares variétés de riz, issues des espèces cultivées de riz africain et asiatique (respectivement Oryza glaberrima et O. sativa), ont récemment été identifiées comme hautement résistantes au RYMV. Ce phénotype de résistance est dû à un gène récessif RYMV1 codant le facteur d'initiation de la traduction eIF(iso)4G1 du riz.Les objectifs de cette thèse sont (i) d'étudier la durabilité de la résistance élevée du riz contre le RYMV avant son déploiement à large échelle, (ii) de caractériser les mécanismes d'émergence de génotypes contournants et (iii) d'identifier des signatures moléculaires influençant ces processus d'adaptation. Ainsi, le contournement de deux allèles de résistance, identifiés chez les deux espèces de riz cultivés, a été relié à l'émergence de mutations dans la protéine virale VPg qui permettent de rétablir l'interaction avec le facteur eIF(iso)4G1 de l'hôte résistant. Un site sous sélection diversificatrice de la VPg influence directement la capacité de contournement de la résistance élevée en fonction de l'espèce hôte. Ce site, proche des mutations de contournement, est impliqué dans l'adaptation du virus à l'espèce O. glaberrima au cours de son histoire évolutive. La démarche employée au cours de ce travail combine des études d'évolution expérimentale à des analyses fonctionnelles. Les résultats obtenus par cette approche intégrative participeront à la mise en place de stratégies de lutte intégrée à la fois efficaces et durables face à la maladie de la panachure jaune du riz en Afrique.

The Rice yellow mottle virus (RYMV) is an emerging virus currently considered as the major constraint to rice production in Africa. Some varieties of African and Asian cultivated rice (Oryza glaberrima and O. sativa, respectively), have recently been identified as highly resistant to RYMV. This resistance phenotype is caused by a recessive gene RYMV1 encoding the translation initiation factor eIF(iso)4G1 of rice.The objectives of this thesis are (i) to investigate the durability of the high resistance of rice against RYMV before broadly deployment in fields, (ii) to characterize the mechanisms of emergence of resistance-breaking (RB) genotypes and (iii) to identify molecular signatures that influence these processes of adaptation. The resistance-breaking of two resistance alleles, identified in both cultivated rice species, is mainly associated with the emergence of mutations in the viral protein VPg that restore in resistant hosts the interaction with the factor eIF(iso)4G1. A site of VPg under diversifying selection directly affects the ability to overcome the high resistance depending on the host species. This site, near the RB mutations, is involved in the adaptation of the RYMV to O. glaberrima species during its evolutionary history. The approach used during this work combines experimental evolution and functional analyses. The results of this…

Advisors/Committee Members: Fargette, Denis (thesis director), Hébrard, Eugénie (thesis director).

Subjects/Keywords: Virus de plante; Émergence; Résistance récessive; Adaptation; Sélection; Interactions moléculaires; Plant virus; Emergence; Recessive resistance; Adaptation; Selection; Molecular interactions

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Poulicard, N. (2010). Emergence et adaptation du Rice yellow mottle virus : relations entre histoire évolutive, contournement de résistance et interactions hôte/pathogène : Emergence and adaptation of Rice yellow mottle virus : relationships between evolutionary history, resistance-breakdown and host/pathogen interactions. (Doctoral Dissertation). Université Montpellier II. Retrieved from http://www.theses.fr/2010MON20121

Chicago Manual of Style (16^th Edition):

Poulicard, Nils. “Emergence et adaptation du Rice yellow mottle virus : relations entre histoire évolutive, contournement de résistance et interactions hôte/pathogène : Emergence and adaptation of Rice yellow mottle virus : relationships between evolutionary history, resistance-breakdown and host/pathogen interactions.” 2010. Doctoral Dissertation, Université Montpellier II. Accessed March 08, 2021. http://www.theses.fr/2010MON20121.

MLA Handbook (7^th Edition):

Poulicard, Nils. “Emergence et adaptation du Rice yellow mottle virus : relations entre histoire évolutive, contournement de résistance et interactions hôte/pathogène : Emergence and adaptation of Rice yellow mottle virus : relationships between evolutionary history, resistance-breakdown and host/pathogen interactions.” 2010. Web. 08 Mar 2021.

Vancouver:

Poulicard N. Emergence et adaptation du Rice yellow mottle virus : relations entre histoire évolutive, contournement de résistance et interactions hôte/pathogène : Emergence and adaptation of Rice yellow mottle virus : relationships between evolutionary history, resistance-breakdown and host/pathogen interactions. [Internet] [Doctoral dissertation]. Université Montpellier II; 2010. [cited 2021 Mar 08]. Available from: http://www.theses.fr/2010MON20121.

Council of Science Editors:

Poulicard N. Emergence et adaptation du Rice yellow mottle virus : relations entre histoire évolutive, contournement de résistance et interactions hôte/pathogène : Emergence and adaptation of Rice yellow mottle virus : relationships between evolutionary history, resistance-breakdown and host/pathogen interactions. [Doctoral Dissertation]. Université Montpellier II; 2010. Available from: http://www.theses.fr/2010MON20121

Freie Universität Berlin

20. Püttmann, Lucia. Identifizierung und Charakterisierung der ursächlichen genetischen Defekte für autosomal rezessive mentale Retardierung in zwei iranischen Familien.

Degree: 2013, Freie Universität Berlin

URL: http://dx.doi.org/10.17169/refubium-14309

► Besonders autosomal-rezessive mentale Retardierung ist durch ausgeprägte Heterogenität gekennzeichnet und umfasst eine große Vielfalt von syndromalen und nicht-syndromalen Formen. Im Rahmen dieser Arbeit wurden zwei… (more)

▼ Besonders autosomal-rezessive mentale Retardierung ist durch ausgeprägte Heterogenität gekennzeichnet und umfasst eine große Vielfalt von syndromalen und nicht-syndromalen Formen. Im Rahmen dieser Arbeit wurden zwei iranische, konsanguine Familien mit mental retardierten Mitgliedern untersucht. Die Patienten der Familie M289 weisen eine mittelschwere Form mentaler Retardierung auf und haben neben grenzwertiger Mikrozephalie keine weiteren Begleitsymptome. Als einzige Mutation mit krankheitsauslösendem Potential wurde die c.514G > A [p.D172N] Sequenzvariante in SARS identifiziert. SARS kodiert die cytoplasmatische Seryl-tRNA-Synthetase, deren Funktion die Beladung von tRNA-Ser und tRNA-Sec mit Serin ist (tRNA-Aminoacylierung). Anhand von in silico-Protein-Modellierung wurde gezeigt, dass p.D172 in der Nähe des aktiven Zentrums von SARS liegt und mit einer negativen Ladung wahrscheinlich zur Aufrechterhaltung einer hydrophoben Umgebung beiträgt. Diese Ladung geht durch die p.D172N-Substitution verloren. Um herauszufinden, ob die p.D172N-Mutation die enzymatische Funktion von SARS beeinträchtigt, wurde die Freisetzung von Pyrophosphat (PPi) während des ersten Reaktionsschritts der tRNA-Aminoacylierung untersucht. Weiterhin wurde mittels Western Blot und Zellfraktionierung gezeigt, dass SARS p.D172N in menschlichen Zellen wahrscheinlich instabil ist. Die Patienten der Familie M8600485 haben ein syndromales Krankheitsbild mit schwerer mentaler Retardierung, Entwicklungsverzögerung, verzögerter Sprachentwicklung und generalisierten tonisch-klonischen Anfällen. Da das Krankheitsbild der Patienten typisch für Succinat-Semialdehyd-Dehydrogense (SSADH)-Defizienz ist, welche durch Mutationen in ALDH5A1 verursacht wird, wurde dieses Gen im Indexpatienten sequenziert. Hierbei wurde die bisher nicht bekannte Missense-Mutation c.901A > G [p.K301E] in ALDH5A1 identifiziert. In silico-Protein-Modellierung dieser Mutation zeigte, dass p.K301E vermutlich zum Verlust der Fähigkeit NAD+ zu binden führt. Zusätzlich konnte berechnet werden, dass die Mutation eine deutliche Abnahme der freien Energie verursacht und damit zu einer starken Destabilisierung von SSADH führen kann. Übereinstimmend mit diesen Vorhersagen wurde der Verlust der SSADH-Enzymaktivität bei unterschiedlichen NAD +–Konzentrationen in Proteinextrakten aus Lymphoblasten eines Patienten aus Familie 8600485 nachgewiesen. Die Mutation p.K301E ist erst die zweite Missense-Mutation, welche die Bindung von NAD+ an SSADH beeinträchtigt und zu nicht nachweisbarer SSADH-Aktivität führt. Advisors/Committee Members: w (gender), Prof. H.H. Ropers (firstReferee), Prof. S. Sigrist (furtherReferee).

Subjects/Keywords: intellectual disability; mental retardation; autosomal; monogenic disorder; recessive inheritance; 500 Naturwissenschaften und Mathematik::570 Biowissenschaften; Biologie::576 Genetik und Evolution

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Püttmann, L. (2013). Identifizierung und Charakterisierung der ursächlichen genetischen Defekte für autosomal rezessive mentale Retardierung in zwei iranischen Familien. (Thesis). Freie Universität Berlin. Retrieved from http://dx.doi.org/10.17169/refubium-14309

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Püttmann, Lucia. “Identifizierung und Charakterisierung der ursächlichen genetischen Defekte für autosomal rezessive mentale Retardierung in zwei iranischen Familien.” 2013. Thesis, Freie Universität Berlin. Accessed March 08, 2021. http://dx.doi.org/10.17169/refubium-14309.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Püttmann, Lucia. “Identifizierung und Charakterisierung der ursächlichen genetischen Defekte für autosomal rezessive mentale Retardierung in zwei iranischen Familien.” 2013. Web. 08 Mar 2021.

Vancouver:

Püttmann L. Identifizierung und Charakterisierung der ursächlichen genetischen Defekte für autosomal rezessive mentale Retardierung in zwei iranischen Familien. [Internet] [Thesis]. Freie Universität Berlin; 2013. [cited 2021 Mar 08]. Available from: http://dx.doi.org/10.17169/refubium-14309.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Püttmann L. Identifizierung und Charakterisierung der ursächlichen genetischen Defekte für autosomal rezessive mentale Retardierung in zwei iranischen Familien. [Thesis]. Freie Universität Berlin; 2013. Available from: http://dx.doi.org/10.17169/refubium-14309

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Freie Universität Berlin

21. Garshasbi, Masoud. Identifizierung von 31 genomischen Loci für autosomal-rezessive geistige Behinderung und molekulargenetische Charakterisierung neuer ursächlicher Mutationen in vier Genen.

Degree: 2010, Freie Universität Berlin

URL: http://dx.doi.org/10.17169/refubium-9548

► Schwere kognitive Erkrankungen und Verhaltensstörungen betreffen ca. 1-3% der Weltbevölkerung und stellen damit eine erhebliche Belastung für die betroffenen Familien, aber auch die Gesellschaft als… (more)

▼ Schwere kognitive Erkrankungen und Verhaltensstörungen betreffen ca. 1-3% der Weltbevölkerung und stellen damit eine erhebliche Belastung für die betroffenen Familien, aber auch die Gesellschaft als Ganzes dar. Es gibt Gründe die dafür sprechen, dass autosomal rezessive Formen mentaler Retardierung (ARMR) häufiger auftreten als X-chromosomal vererbte Formen geistiger Behinderung, jedoch bisher weniger Aufmerksamkeit erfahren haben. Dies liegt zum Teil daran, dass in industrialisierten Gesellschaften die dort vorherrschenden kleinen Familien und der geringe Grad an Konsanguinität in der Bevölkerung die Genkartierung behindert haben. Veranschaulicht wird dieser Sachverhalt durch die Tatsache, dass zu Beginn dieser Studie im Jahr 2003 nur ein Gen für nicht-syndromale mentale Retardierung (NS-ARMR) bekannt war. Die hier vorgestellte Arbeit ist Teil eines größer angelegten Projekts zur Aufklärung der molekularen Ursachen geistiger Behinderung in konsanguinen iranischen Großfamilien mit mehreren mental retardierten Kindern, um damit die Voraussetzungen für Diagnose, Beratung und Therapie zu verbessern. Diese Studie verbindet klinische und molekulargenetische Untersuchungsmethoden wie Patientenrekrutierung, klinische Charakterisierung, Probensammlung, SNP-array Genotypisierung, genomweite Kopplungsanalyse, Homozygotiekartierung und Mutationsanalyse auf systematische Art und Weise. Auf erfolgreiche Mutationsanalysen folgen schließlich Untersuchungen zur Funktion betroffener Gene. In der hier vorgestellten Arbeit führte die Untersuchung von 135 Familien zur Identifizierung von 31 neuen Loci für ARMR. Im Gegensatz zu früheren Beobachtungen, welche zunächst gegen die Existenz häufig mutierter Gene sprachen, wurden nun überlappende autozygote Bereiche von mehren Familien auf den Chromosomen 1, 5 und 19 gefunden. An jedem dieser Loci waren mindestens zwei der überlappenden Intervalle die einzigen in den jeweiligen Familien und zeigten einen LOD Score von drei oder höher. Die Mutationsanalyse in einer dieser Familien mit NS-ARMR führte zur Entdeckung eines neuen Gens für NS-ARMR, TUSC3, in welchem eine Mutation gefunden wurde, die den Verlust des zugehörigen Transkripts in Patientenzellen zur Folge hat. Weitere Untersuchungen von Familien mit syndromalen Fromen mentaler Retardierung brachten ein neues Gen für Ataxie mit milder geistiger Behinderung zu Tage. In diesem Gen, CA8, tragen die betroffenen Patienten eine R237Q Mutation mit mutmaßlich stark einschränkenden Auswirkungen auf die Funktion des Genprodukts. Des Weiteren wurde eine neue Muation im ALDH3A2 Gen von Patienten mit Sjögren-Larsson Syndrom, sowie zwei bisher unbekannte Mutationen im MCPH1 Gen von Patienten mit primärer Mikrozephalie gefunden. Genomweite Genexpressionsuntersuchungen, Knockdown- Experimente und Bestrahlungsversuche lieferten neue Erkenntnisse über die Beteiligung von MCPH1 an der Zellzykluskontrolle, bei zellulären DNA-Reparatursystemen und Transkriptionsregulation. Zusammenfassend kann gesagt werden, dass die Identifizierung eines neuen Gens für… Advisors/Committee Members: [email protected] (contact), [email protected] (contact), n (gender), Prof. Dr. Hans Hilger Ropers (firstReferee), Prof. Dr. Volker A. Erdmann (furtherReferee).

Subjects/Keywords: Linkage Analysis; Autosomal Recessive Mental Retardation; TUSC3; MCPH1; CA8; ALDH3A2; 500 Naturwissenschaften und Mathematik::570 Biowissenschaften; Biologie::576 Genetik und Evolution

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Garshasbi, M. (2010). Identifizierung von 31 genomischen Loci für autosomal-rezessive geistige Behinderung und molekulargenetische Charakterisierung neuer ursächlicher Mutationen in vier Genen. (Thesis). Freie Universität Berlin. Retrieved from http://dx.doi.org/10.17169/refubium-9548

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Garshasbi, Masoud. “Identifizierung von 31 genomischen Loci für autosomal-rezessive geistige Behinderung und molekulargenetische Charakterisierung neuer ursächlicher Mutationen in vier Genen.” 2010. Thesis, Freie Universität Berlin. Accessed March 08, 2021. http://dx.doi.org/10.17169/refubium-9548.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Garshasbi, Masoud. “Identifizierung von 31 genomischen Loci für autosomal-rezessive geistige Behinderung und molekulargenetische Charakterisierung neuer ursächlicher Mutationen in vier Genen.” 2010. Web. 08 Mar 2021.

Vancouver:

Garshasbi M. Identifizierung von 31 genomischen Loci für autosomal-rezessive geistige Behinderung und molekulargenetische Charakterisierung neuer ursächlicher Mutationen in vier Genen. [Internet] [Thesis]. Freie Universität Berlin; 2010. [cited 2021 Mar 08]. Available from: http://dx.doi.org/10.17169/refubium-9548.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Garshasbi M. Identifizierung von 31 genomischen Loci für autosomal-rezessive geistige Behinderung und molekulargenetische Charakterisierung neuer ursächlicher Mutationen in vier Genen. [Thesis]. Freie Universität Berlin; 2010. Available from: http://dx.doi.org/10.17169/refubium-9548

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Freie Universität Berlin

22. Duncker, Tobias. Korrelationen zwischen Nah-Infrarot und kurzwelliger Autofluoreszenz und Spektral-Domänen optische Kohärenztomografie in Morbus Stargardt.

Degree: 2015, Freie Universität Berlin

URL: https://refubium.fu-berlin.de/handle/fub188/13396

► Einleitung: Es wird davon ausgegangen, dass die kurzwellige Fundusautofluoreszenz (SW-AF) von Lipofuszin im retinalen Pigmentepithel (RPE) hervorgerufen wird und die Nahinfrarot-Fundusautofluoreszenz (NIR-AF) von Melanin. Bei… (more)

▼ Einleitung: Es wird davon ausgegangen, dass die kurzwellige Fundusautofluoreszenz (SW-AF) von Lipofuszin im retinalen Pigmentepithel (RPE) hervorgerufen wird und die Nahinfrarot-Fundusautofluoreszenz (NIR-AF) von Melanin. Bei Patienten mit Morbus Stargardt (STGD1) wurden SW-AF und NIR-AF mit durch optische Kohärenztomographie (SD-OCT) gewonnenen strukturellen Informationen korreliert. Methodik: Vierundzwanzig STGD1 Patienten (45 Augen; Alter: 8-61 Jahre) mit nachgewiesenen krankheits-assoziierten ABCA4 Mutationen wurden prospektiv untersucht. SW-AF, NIR-AF und SD-OCT Aufnahmen wurden generiert. Ergebnisse: Fünf Phänotypen wurden identifiziert basierend auf Charakteristika der zentralen Läsion und Ausdehnung der Fundusveränderungen. Zentrale Areale mit reduziertem NIR-AF Signal waren typischerweise größer als Areale mit reduziertem SW-AF Signal und das reduzierte NIR-AF Signal zeigte meistens Übereinstimmung mit Arealen in den SD-OCT Aufnahmen, in denen die ellipsoid zone (EZ) verloren gegangen war (Gruppe 1; r, 0.93, p<0.0001). Bei Patienten, die eine zentrale Läsion mit sich überlappenden parafovealen Ringen mit erhöhtem NIR-AF und SW-AF Signal haben (Gruppe 3), war der EZ Verlust stark korreliert mit dem inneren Durchmesser des NIR-AF Ringes (r, 0.89, p<0.0001) und der äußere Rand des NIR-AF Ringes lag weiter peripher als der äußere Rand des SW-AF Ringes. Schlussfolgerungen: Die Läsionsareale waren besser abgrenzbar in NIR-AF Aufnahmen als in SW-AF Aufnahmen. In den meisten Fällen zeigte sich ein EZ Verlust nur an Orten, wo NIR-AF vermindert oder erloschen war, was darauf hindeutet, dass es in der Pathogenese von STGD1 zuerst zur RPE Atrophie und dann zur Degeneration von Photorezeptoren kommt. Da innerhalb des zentralen Fundusareals mit EZ Verlust SW-AF häufig erhöht war, könnten degenerierende Photorezeptoren Lipofuszin beschleunigt produzieren. Es werden Mechanismen erörtert, die einem erhöhten NIR-AF Signal in Verbindung mit einem erhöhten SW-AF Signal zugrunde liegen könnten. Advisors/Committee Members: m (gender), N.N. (firstReferee), N.N. (furtherReferee).

Subjects/Keywords: ABCA4; fundus autofluorescence; lipofuscin; melanin; optical coherence tomography; recessive Stargardt disease; 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Duncker, T. (2015). Korrelationen zwischen Nah-Infrarot und kurzwelliger Autofluoreszenz und Spektral-Domänen optische Kohärenztomografie in Morbus Stargardt. (Thesis). Freie Universität Berlin. Retrieved from https://refubium.fu-berlin.de/handle/fub188/13396

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Duncker, Tobias. “Korrelationen zwischen Nah-Infrarot und kurzwelliger Autofluoreszenz und Spektral-Domänen optische Kohärenztomografie in Morbus Stargardt.” 2015. Thesis, Freie Universität Berlin. Accessed March 08, 2021. https://refubium.fu-berlin.de/handle/fub188/13396.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Duncker, Tobias. “Korrelationen zwischen Nah-Infrarot und kurzwelliger Autofluoreszenz und Spektral-Domänen optische Kohärenztomografie in Morbus Stargardt.” 2015. Web. 08 Mar 2021.

Vancouver:

Duncker T. Korrelationen zwischen Nah-Infrarot und kurzwelliger Autofluoreszenz und Spektral-Domänen optische Kohärenztomografie in Morbus Stargardt. [Internet] [Thesis]. Freie Universität Berlin; 2015. [cited 2021 Mar 08]. Available from: https://refubium.fu-berlin.de/handle/fub188/13396.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Duncker T. Korrelationen zwischen Nah-Infrarot und kurzwelliger Autofluoreszenz und Spektral-Domänen optische Kohärenztomografie in Morbus Stargardt. [Thesis]. Freie Universität Berlin; 2015. Available from: https://refubium.fu-berlin.de/handle/fub188/13396

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Freie Universität Berlin

23. Falahkohan, Sepiede. Retrograde scientometric analysis of the scientific role of Cystic Fibrosis.

Degree: 2011, Freie Universität Berlin

URL: http://dx.doi.org/10.17169/refubium-11839

► Cystic Fibrosis is an inheritable autosomal recessive disease and one of the most frequent metabolism diseases of Europe’s and North America’s white population. Cystic Fibrosis… (more)

▼ Cystic Fibrosis is an inheritable autosomal recessive disease and one of the most frequent metabolism diseases of Europe’s and North America’s white population. Cystic Fibrosis is a complex, multisystemic disease, which mainly affects the gastrointestinal tract and the lung. Due to continuous progress in understanding CF and a subsequent advancement of its therapy and its medical treatment during the last 20 years today’s patients can benefit from a higher expectancy of life as well as from an improved quality of life. The aim of the present analysis was to assess and to compare research output in cystic fibrosis research over the past decades. A large database analysis was performed using the ISI-Web of Science sources from Thomson Reuters. The period of analysis was 1900 to 2009. Mathematical algorithms, system diagrams and density-equalizing mapping procedures were used to visualize database searches. A total of 37.467 entries at ISI Web were registered in the above- named period. 95% of these entries were published in English. A country- ranking of the total numbers of entries lists the United States in first position, followed by England. The United States are leading too with regard to the number of citations and the h-Index. When average citations per item were analyzed, Canada is leading. The majority of research institutions and cooperative works has its origins in the USA. Canada and Great Britain are the main cooperative partner countries. The most common publication type to impart the knowledge on cystic fibrosis was the article type (64%), followed by the meeting abstracts (12%) and the reviews (8%). Microbiology, the respiratory system as well as pharmacology and pharmacy are among the leading subjects correlated with cystic fibrosis. The journal Pediatric Pulmonology has published the most articles (1.344) to deal with cystic fibrosis. Renowned journals as The Lancet or The Journal of Biological Chemistry are among the most publishing journals. The Danish professor Niels Hoiby is the most productive author with a total of 265 publications. When the quantity of citations and the average citations per item of the authors are considered the Chinese professor of genetics Lap-Chee Tsui holds this position. The American professor for medicine Richard Boucher reveals to have the highest h-Index. The present data indicates the prominent role of cystic fibrosis research in respiratory medicine. Throughout the past 20 years there is a continuous increase in research activity that reflects an enormous advance in the knowledge about this disease. Geographically, North America holds the leading position in many categories and is followed by a number of European countries. Advisors/Committee Members: w (gender), Prof. Dr. Dr. h. c. mult. D. Groneberg (firstReferee), Priv.-Doz. Dr. med. habil. I. Böckelmann (furtherReferee), Prof. Dr. med. T. Kraus (furtherReferee).

Subjects/Keywords: cystic fibrosis; scientometric analysis; h- index; autosomal recessive disease; 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Falahkohan, S. (2011). Retrograde scientometric analysis of the scientific role of Cystic Fibrosis. (Thesis). Freie Universität Berlin. Retrieved from http://dx.doi.org/10.17169/refubium-11839

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Falahkohan, Sepiede. “Retrograde scientometric analysis of the scientific role of Cystic Fibrosis.” 2011. Thesis, Freie Universität Berlin. Accessed March 08, 2021. http://dx.doi.org/10.17169/refubium-11839.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Falahkohan, Sepiede. “Retrograde scientometric analysis of the scientific role of Cystic Fibrosis.” 2011. Web. 08 Mar 2021.

Vancouver:

Falahkohan S. Retrograde scientometric analysis of the scientific role of Cystic Fibrosis. [Internet] [Thesis]. Freie Universität Berlin; 2011. [cited 2021 Mar 08]. Available from: http://dx.doi.org/10.17169/refubium-11839.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Falahkohan S. Retrograde scientometric analysis of the scientific role of Cystic Fibrosis. [Thesis]. Freie Universität Berlin; 2011. Available from: http://dx.doi.org/10.17169/refubium-11839

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Freie Universität Berlin

24. Hoffer, Julia Leonie. moleculargenetic investigations on two autosomal recessive disorders.

Degree: 2016, Freie Universität Berlin

URL: http://dx.doi.org/10.17169/refubium-4960

► This thesis focuses on the investigation and comparison of a non-syndromic and a syndromic genetic disorder, which both are of autosomal recessive inheritance: non-syndromic intellectual… (more)

▼ This thesis focuses on the investigation and comparison of a non-syndromic and a syndromic genetic disorder, which both are of autosomal recessive inheritance: non-syndromic intellectual disability and cranioectodermal dysplasia. Intellectual disability is a prevalent disorder attributable to various, genetic as well as non-genetic, origins. Non-syndromic intellectual disability designates the solitary symptom of intellectual disability without any other conspicuous malformations or dysmorphic signs presenting as features of a syndromic disorder. For this entity, underlying genetic mutations seem to be innumerable and spread over the whole genome. In seven large consanguineous families with autosomal recessive intellectual disability, homozygosity mapping, targeted exon enrichment, and high throughput sequencing resulted in an identification of the underlying genetic defect in each of the seven families. These results demonstrate the vast heterogeneity of the underlying genetics. The second disorder presented is cranioectodermal dysplasia, a rare syndromic disorder belonging to the group of ciliopathies. Symptoms comprise sceletal and ectodermal dysmorphia such as dolichocephaly, rhizomelic limb shortening, dental abnormalities and impairment of renal and liver function, causing early-onset organ failure. So far, a few mutations have been detected in the protein complex required for dynein-driven retrograde ciliary transport, IFT-A. Cilia are known as propulsive motors and organelles for cell communication. In nine patients with cranioectodermal dysplasia, two protein- coding genes of the IFT-A complex have been analyzed (WDR35 and IFT43). Three different and yet unknown mutations were detected in WDR35 in two patients. The findings indicate that cranioectodermal dysplasia is a genetically as well as phenotypically heterogenous ciliopathy. Future investigation on function and genetics of the IFT-A complex could further illuminate the underlying pathogenesis of cranioectodermal dysplasia. The affected families will benefit from a definite diagnosis often ending a diagnostic odyssey. The new insights will facilitate the understanding of the clinical course and could make possible prenatal diagnosis and carrier testing of unaffected individuals. Advisors/Committee Members: w (gender), N.N. (firstReferee), N.N. (furtherReferee).

Subjects/Keywords: intellectual disability; cranioectodermal dysplasia; autosomal recessive disorder; 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Hoffer, J. L. (2016). moleculargenetic investigations on two autosomal recessive disorders. (Thesis). Freie Universität Berlin. Retrieved from http://dx.doi.org/10.17169/refubium-4960

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Hoffer, Julia Leonie. “moleculargenetic investigations on two autosomal recessive disorders.” 2016. Thesis, Freie Universität Berlin. Accessed March 08, 2021. http://dx.doi.org/10.17169/refubium-4960.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Hoffer, Julia Leonie. “moleculargenetic investigations on two autosomal recessive disorders.” 2016. Web. 08 Mar 2021.

Vancouver:

Hoffer JL. moleculargenetic investigations on two autosomal recessive disorders. [Internet] [Thesis]. Freie Universität Berlin; 2016. [cited 2021 Mar 08]. Available from: http://dx.doi.org/10.17169/refubium-4960.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Hoffer JL. moleculargenetic investigations on two autosomal recessive disorders. [Thesis]. Freie Universität Berlin; 2016. Available from: http://dx.doi.org/10.17169/refubium-4960

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

National University of Ireland – Galway

25. Aied, Ahmed. Design and development of polymeric transfection vectors for gene delivery in Recessive Dystrophic Epidermolysis Bullosa .

Degree: 2014, National University of Ireland – Galway

URL: http://hdl.handle.net/10379/4569

► Recessive Dystrophic Epidermolysis Bullosa (RDEB) is caused by mutations in the collagen VII gene (COL7A1) that lead to an alteration of function or a reduction… (more)

▼ Recessive Dystrophic Epidermolysis Bullosa (RDEB) is caused by mutations in the collagen VII gene (COL7A1) that lead to an alteration of function or a reduction in the amounts of collagen VII protein (C7). Any of these mutations will impair C7 assembly into anchoring fibrils that anchor the basement membrane zone (BMZ) to the underlying dermis. This in turn causes reduced skin resistance to mild trauma making the patients suffer from severe blistering and scarring in the skin and mucosa. Intensive efforts are being made to restore the anchoring protein at the BMZ as a means of providing a lasting cure for the disease. One of the methods examined as potential therapy utilizes viral vectors for genetic correction of the C7 expressing cells. However, toxicity and immunogenicity concerns have halted progress using viral vectors for gene therapy in many clinical trials. As a result, non-viral methods of delivery have attracted great interest as a replacement. The overall aim of this project was to develop a safe and efficient polymer based gene delivery method to encourage the production of functional C7 protein and restore the mechanical stability at the BMZ in RDEB mouse skin. We focused on one of the more versatile methods of non-viral based delivery that utilizes a dense polycation synthesized from deactivation-enhanced atom transfer radical polymerisation (multi-knot) or Michael addition (hyperbranched poly ([beta]-amino ester)). The polymers were created to deliver the therapeutic C7 plasmid DNA to RDEB keratinocytes and fibroblasts. The focus was mainly on keratinocytes and fibroblasts since they are the predominant cells found in the upper dermis and epidermis, and perhaps contribute more to C7 expression than any other group of cells. Using specially designed cationic polymers, we were able to restore some of the C7 expression in vitro and in RDEB skin equivalents (SEs) (3D organ cultures). SEs are being used to test for toxicity and effectiveness of many drugs, reducing the need for pre-clinical trials. Unfortunately, SEs do not fully replicate natural tissues, because they lack the complexity and array of cells and proteins found in natural tissue. In addition, the presence of immune response capability and blood circulation in pre-clinical models will give a more accurate account of the drug's safety. This encouraged us to test the effectiveness of polymer vectors for COL7A1 delivery in an in vivo pre-clinical model of RDEB. We used Col7[alpha] 1 null RDEB (Col7[alpha]1-/-) knockout mice (developed from immune-competent mice by targeted inactivation of Col7[alpha]1) to test our hypothesis. Clinically, these mice showed severe blistering and detachment of the epidermis from the dermis after birth similar to the human phenotype. We successfully observed expression of the therapeutic transgene product (C7) in the mice after intradermal injection of the HPAE/COL7A1 complex into the mouse paws and ventral region, although there was a noticeable inflammatory response around the injected area. This new approach has… Advisors/Committee Members: Wang, Wenxin (advisor).

Subjects/Keywords: Transfection; Collagen VII; Recessive Dystrophic Epidermolysis Bullosa; Gene therapy; Polymer synthesis; Cationic polymers; Wound healing; Network of Excellence for Functional Biomaterials

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Aied, A. (2014). Design and development of polymeric transfection vectors for gene delivery in Recessive Dystrophic Epidermolysis Bullosa . (Thesis). National University of Ireland – Galway. Retrieved from http://hdl.handle.net/10379/4569

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Aied, Ahmed. “Design and development of polymeric transfection vectors for gene delivery in Recessive Dystrophic Epidermolysis Bullosa .” 2014. Thesis, National University of Ireland – Galway. Accessed March 08, 2021. http://hdl.handle.net/10379/4569.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Aied, Ahmed. “Design and development of polymeric transfection vectors for gene delivery in Recessive Dystrophic Epidermolysis Bullosa .” 2014. Web. 08 Mar 2021.

Vancouver:

Aied A. Design and development of polymeric transfection vectors for gene delivery in Recessive Dystrophic Epidermolysis Bullosa . [Internet] [Thesis]. National University of Ireland – Galway; 2014. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/10379/4569.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Aied A. Design and development of polymeric transfection vectors for gene delivery in Recessive Dystrophic Epidermolysis Bullosa . [Thesis]. National University of Ireland – Galway; 2014. Available from: http://hdl.handle.net/10379/4569

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

26. Uddin, Md Mesbah. Identification of causal factors for recessive lethals in dairy cattle with special focus on large chromosomal deletions : Etude de délétions chromosomiques et de variants génétiques responsables de mortalité embryonnaire chez les bovins laitiers.

Degree: Docteur es, Génétique animale, 2019, Paris, Institut agronomique, vétérinaire et forestier de France; Aarhus universitet (Danemark)

URL: http://www.theses.fr/2019IAVF0018

► L'objectif général de cette thèse est d'identifier les variants causaux ou, à défaut, un ensemble de marqueurs prédictifs - qui présentent un déséquilibre de liaison… (more)

▼ L'objectif général de cette thèse est d'identifier les variants causaux ou, à défaut, un ensemble de marqueurs prédictifs - qui présentent un déséquilibre de liaison élevé avec les variants causaux - pour la fertilité des vaches laitières. Nous avons abordé cet objectif général dans cinq articles: (i) décrit une approche systématique de cartographie des variants létaux récessifs chez les bovins Normands français basée sur la recherche de déficit en haplotypes homozygotes (HHD). Cette étude montre l’influence de la taille de l’échantillon, de la qualité des génotypes, de la qualité du phasage des génotypes en haplotypes et de l’imputation, de l’âge de l’haplotype et enfin, de la définition des seuils de signification prenant en compte les tests multiples, sur la découverte et la reproductibilité des résultats de HHD. Elle illustre également l’importance de la cartographie fine avec les données de généalogie et de séquence de génome entier (WGS), l’annotation intégrative (entre espèces) pour hiérarchiser les mutations candidates et, enfin, le génotypage à grande échelle de la mutation candidate, pour valider ou invalider les mutations initiales. (ii) décrit une cartographie à haute résolution de grandes délétions chromosomiques de séquences du génome dans une population de 175 animaux appartenant à trois races laitières nordiques. Cette étude utilise trois approches différentes pour valider les résultats de la cartographie. Le chapitre décrit les propriétés génétiques des populations et l’importance fonctionnelle des délétions identifiées. (iii) traite de trois questions liées à l’imputation de variants structuraux, ici de délétions chromosomiques importantes: la disponibilité des génotypes de délétion, la taille du panel de référence d'haplotypes et, enfin, l’imputation elle-même. Pour aborder les deux premières questions, cette étude décrit une approche basée sur un modèle de mélange gaussien dans laquelle les données de profondeur de lecture provenant de fichiers au format VCF (variant call format) sont utilisées pour génotyper un locus de délétion connu, en l’absence d’information sur la séquence brute. Enfin, il présente un pipeline pour l'imputation conjointe de variants WGS et de grandes délétions chromosomiques. (iv) décrit des études d'association pangénomiques de la fertilité femelle dans trois races de bovins laitiers nordiques à l'aide de variants WGS imputés et de grandes délétions chromosomiques. Cette étude concerne huit caractères de fertilité et utilise des analyses d'association mono-marqueur, conditionnelles et conjointes. Cette étude montre qu’une surestimation, ou « inflation », des statistiques de test peut être observée même après correction pour la stratification de la population à l'aide de composantes principales génomiques et pour les structures familiales à l'aide de matrices de relations génomiques. Ce biais était connu pour les caractères très polygéniques. Enfin, cette étude présente plusieurs locus de traits quantitatifs (QTL) nouveaux et confirme plusieurs autres déjà connus. Elle… Advisors/Committee Members: Boichard, Didier (thesis director), Goutam, Sahana (thesis director).

Subjects/Keywords: Mortalité embryonnaire; Variations structurales; Bovins laitiers; Sélection génomique; Recessive lethal; Structural variants; Dairy cattle; Genomic prediction; 636.0821

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Uddin, M. M. (2019). Identification of causal factors for recessive lethals in dairy cattle with special focus on large chromosomal deletions : Etude de délétions chromosomiques et de variants génétiques responsables de mortalité embryonnaire chez les bovins laitiers. (Doctoral Dissertation). Paris, Institut agronomique, vétérinaire et forestier de France; Aarhus universitet (Danemark). Retrieved from http://www.theses.fr/2019IAVF0018

Chicago Manual of Style (16^th Edition):

Uddin, Md Mesbah. “Identification of causal factors for recessive lethals in dairy cattle with special focus on large chromosomal deletions : Etude de délétions chromosomiques et de variants génétiques responsables de mortalité embryonnaire chez les bovins laitiers.” 2019. Doctoral Dissertation, Paris, Institut agronomique, vétérinaire et forestier de France; Aarhus universitet (Danemark). Accessed March 08, 2021. http://www.theses.fr/2019IAVF0018.

MLA Handbook (7^th Edition):

Uddin, Md Mesbah. “Identification of causal factors for recessive lethals in dairy cattle with special focus on large chromosomal deletions : Etude de délétions chromosomiques et de variants génétiques responsables de mortalité embryonnaire chez les bovins laitiers.” 2019. Web. 08 Mar 2021.

Vancouver:

Uddin MM. Identification of causal factors for recessive lethals in dairy cattle with special focus on large chromosomal deletions : Etude de délétions chromosomiques et de variants génétiques responsables de mortalité embryonnaire chez les bovins laitiers. [Internet] [Doctoral dissertation]. Paris, Institut agronomique, vétérinaire et forestier de France; Aarhus universitet (Danemark); 2019. [cited 2021 Mar 08]. Available from: http://www.theses.fr/2019IAVF0018.

Council of Science Editors:

Uddin MM. Identification of causal factors for recessive lethals in dairy cattle with special focus on large chromosomal deletions : Etude de délétions chromosomiques et de variants génétiques responsables de mortalité embryonnaire chez les bovins laitiers. [Doctoral Dissertation]. Paris, Institut agronomique, vétérinaire et forestier de France; Aarhus universitet (Danemark); 2019. Available from: http://www.theses.fr/2019IAVF0018

University of Minnesota

27. Lee, Catherine. Applications of Next-Generation Sequencing to Rare Disease.

Degree: PhD, Molecular, Cellular, Developmental Biology and Genetics, 2018, University of Minnesota

URL: http://hdl.handle.net/11299/200310

► Since the discovery of the structure of DNA in 1953, researchers and clinicians have been painstakingly paving the way for the use of genetic information… (more)

▼ Since the discovery of the structure of DNA in 1953, researchers and clinicians have been painstakingly paving the way for the use of genetic information in the treatment of disease. In order for this to be possible, specific genetic targets must be identified. For this dissertation, I use next generation, single-cell, and third generation RNA-sequencing techniques to identify markers of genetic heterogeneity and potential therapeutic targets in the rare diseases recessive dystrophic epidermolysis bullosa (RDEB) and cerebral childhood adrenoleukodystrophy (ccALD). RDEB is a an inherited blistering disorder caused by mutations in the key structural skin protein, type VII collagen (C7). It can partially treated by hematopoietic stem cell transplant (HSCT), however, how blistered RDEB skin signals to donor cells is unknown. In Chapter 2, to identify potential signals, I performed single-cell RNA-seq (scRNA-seq) on patient fibroblasts and implemented a variance-driven multitask clustering (scVDMC), that utilizes multiple single-cell populations from biological replicates or different samples. scVDMC clusters single cells in multiple scRNA-seq experiments of similar cell types and markers but varying expression patterns such that the scRNA-seq data are better integrated than typical pooled analyses which only increase the sample size. By controlling the variance among the cell clusters within each dataset and across all the datasets, scVDMC detects cell sub-populations in each individual experiment with shared cell-type markers but varying cluster centers among all the experiments. scVDMC was then applied to two previously published scRNA-seq datasets with several replicates and one large-scale Drop-seq dataset on three patient samples. scVDMC more accurately detected cell populations and known cell markers than pooled clustering and other recently proposed scRNA-seq clustering methods. When applied to the scRNA-seq RDEB patient fibroblast data, scVDMC revealed several new cell types and unknown markers that I validated by flow cytometry. ccALD is caused by mutations in the \emph{ABCD1} gene and manifests in early childhood with neuropathological symptoms and hyper-pigmentation, culminating in massive breakdown of the blood-brain barrier (BBB) and death if HSCT is not performed at an early stage. It is difficult to model the BBB of this disease as primary cells do not recapitulate the barrier in culture and the mouse model shows incomplete penetrance. In Chapter 3, I model the blood-brain barrier of ccALD patients and wild-type (WT) controls using directed differentiation of induced pluripotent stem cells (iPSCs) into induced brain microvascular endothelial cells (iBMECs). Immunocytochemistry and PCR confirmed characteristic expression of brain microvascular endothelial cell (BMEC) markers. Barrier properties of iBMECs were measured via trans-endothelial electrical resistance (TEER), sodium fluorescein permeability, and frayed junction analysis. Electron microscopy and RNA-seq were used to further characterize…

Subjects/Keywords: Adrenoleukodystrophy; Brain Microvascular Endothelial Cells; Rare Disease; Recessive Dystrophic Epidermolysis Bullosa; Revertant Mosaicism; Single-cell RNA-seq

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Lee, C. (2018). Applications of Next-Generation Sequencing to Rare Disease. (Doctoral Dissertation). University of Minnesota. Retrieved from http://hdl.handle.net/11299/200310

Chicago Manual of Style (16^th Edition):

Lee, Catherine. “Applications of Next-Generation Sequencing to Rare Disease.” 2018. Doctoral Dissertation, University of Minnesota. Accessed March 08, 2021. http://hdl.handle.net/11299/200310.

MLA Handbook (7^th Edition):

Lee, Catherine. “Applications of Next-Generation Sequencing to Rare Disease.” 2018. Web. 08 Mar 2021.

Vancouver:

Lee C. Applications of Next-Generation Sequencing to Rare Disease. [Internet] [Doctoral dissertation]. University of Minnesota; 2018. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/11299/200310.

Council of Science Editors:

Lee C. Applications of Next-Generation Sequencing to Rare Disease. [Doctoral Dissertation]. University of Minnesota; 2018. Available from: http://hdl.handle.net/11299/200310

28. Olteanu, Dragos S. Dysregulated ENAC and NHE function in cilium-deficient renal collecting duct cell monolayers : a model of polycystic kidney disease.

Degree: PhD, 2007, University of Alabama – Birmingham

URL: http://contentdm.mhsl.uab.edu/u?/etd,610

►

Polycystic kidney disease in both its recessive and dominant forms involves the remodeling of the kidney and extra-renal tissues where parts of the tissue break… (more)

▼

Polycystic kidney disease in both its recessive and dominant forms involves the remodeling of the kidney and extra-renal tissues where parts of the tissue break contact with the normal tissue as “pseudocysts” or fully encapsulated and fluid-filled cysts. Once this remodeling into “cystic” tissue has occurred, the secondary progression of the disease is influenced dramatically by salt and water transport and by autocrine and paracrine factors that become trapped in these abnormal cystic microenvironments. During this progression, hypertension develops ahead of renal decline. In recessive PKD (ARPKD), there is early onset hypertension in neonatal and pediatric patients that is severe and debilitating. My research has focused on cilium-deficient cortical collecting duct principal cell models of PKD from the Tg737orpk mouse. My work is being extended to conditional cilium-deficient cell models as well as the mouse models from which these cells were derived. I have found that ENaC is 4-fold upregulated in cilium-deficient versus cilium-competent cell monolayers. This upregulation may be central to the rapid development of hypertension. In parallel, there is inappropriate mislocalization of sodium/hydrogen (Na/H) exchange (NHE) in the apical membrane of cilium-deficient cell monolayers versus controls. Together, apical NHE activity with ENaC upregulation may contribute marked Na+ hyperabsorption leading to hypertension in ARPKD and, perhaps, ADPKD patients. This cilium-deficient pathology creates an intriguing pathophysiology where NHEs and ENaC are in the same apical membrane domain in principal cells. Apical NHE activity would fuel ENaC activity via extracellular acidification and intracellular alkalinization. Metabolic pH measurements of freshly voided urine showed enhanced acidification in the mutant mice at all ages between 1 and 4 weeks. Metabolic alkalosis developed at 4 weeks of age. My future work will seek to understand why the loss of a sensory organelle, the primary or central monocilium, leads to upregulation of salt and water reabsorption in terms of epithelial cell pathophysiology. Steps designed to quell salt hyperabsorption may be beneficial in controlling the establishment and progression of cystic kidney disease in humans.

1 online resource (xii, 227 p. : ill., digital, PDF file)

Physiology and Biophysics

Joint Health Sciences;

kidney cell physiology sodium transport polycystic kidney disease epithelial cell acid-base transport

UNRESTRICTED

Advisors/Committee Members: Schwiebert, Erik M., Bevensee, Mark O.<br>, Clancy, John P.<br>, Smith, Peter R.<br>, Yoder, Bradley K..

Subjects/Keywords: Cilia – metabolism<; br>; Epithelial Cells<; br>; Kidney<; br>; Polycystic Kidney, Autosomal Recessive – metabolism<; br>; Sodium – metabolism<; br>; Sodium Channels – metabolism

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Olteanu, D. S. (2007). Dysregulated ENAC and NHE function in cilium-deficient renal collecting duct cell monolayers : a model of polycystic kidney disease. (Doctoral Dissertation). University of Alabama – Birmingham. Retrieved from http://contentdm.mhsl.uab.edu/u?/etd,610

Chicago Manual of Style (16^th Edition):

Olteanu, Dragos S. “Dysregulated ENAC and NHE function in cilium-deficient renal collecting duct cell monolayers : a model of polycystic kidney disease.” 2007. Doctoral Dissertation, University of Alabama – Birmingham. Accessed March 08, 2021. http://contentdm.mhsl.uab.edu/u?/etd,610.

MLA Handbook (7^th Edition):

Olteanu, Dragos S. “Dysregulated ENAC and NHE function in cilium-deficient renal collecting duct cell monolayers : a model of polycystic kidney disease.” 2007. Web. 08 Mar 2021.

Vancouver:

Olteanu DS. Dysregulated ENAC and NHE function in cilium-deficient renal collecting duct cell monolayers : a model of polycystic kidney disease. [Internet] [Doctoral dissertation]. University of Alabama – Birmingham; 2007. [cited 2021 Mar 08]. Available from: http://contentdm.mhsl.uab.edu/u?/etd,610.

Council of Science Editors:

Olteanu DS. Dysregulated ENAC and NHE function in cilium-deficient renal collecting duct cell monolayers : a model of polycystic kidney disease. [Doctoral Dissertation]. University of Alabama – Birmingham; 2007. Available from: http://contentdm.mhsl.uab.edu/u?/etd,610

University of Oulu

29. Majava, M. (Marja). Molecular genetics of Stickler and Marshall syndromes, and the role of collagen II and other candidate proteins in high myopia and impaired hearing.

Degree: 2007, University of Oulu

URL: http://urn.fi/urn:isbn:9789514283628

► Abstract Stickler and Marshall syndromes are genetic disorders both inherited in an autosomal dominant manner. The genotype-phenotype correlation was performed in ten Stickler/Marshall syndrome patients… (more)

▼ Abstract Stickler and Marshall syndromes are genetic disorders both inherited in an autosomal dominant manner. The genotype-phenotype correlation was performed in ten Stickler/Marshall syndrome patients with mutations in the COL11A1 gene. Four patients had a phenotype classified as Marshall syndrome based on early-onset severe hearing loss and characteristic facial dysmorphism. A splice site mutation in intron 50 of COL11A1 was found in these patients, while the remaining six patients had an overlapping Marshall-Stickler phenotype with a mutation elsewhere in the gene. These results indicate exon 50 as a hot spot for splice site mutations leading to a phenotype of Marshall syndrome rather than Stickler syndrome. Collagen II (COL2A1) precursor mRNA undergoes alternative splicing resulting in two different isoforms, IIA including exon 2 and IIB excluding exon 2. Recent evidence indicates that premature termination codon mutations in exon 2 cause Stickler syndrome with no or minimal extraocular manifestations. Two mutations were observed in this study: Cys64Stop, and a novel structural mutation, Cys57Tyr. Results from the COL2A1 mini-gene studies suggested that both mutations altered positive cis elements for splicing resulting in a lower IIA:IIB ratio. The results further emphasize the importance of exon 2 in the development and normal function of the eye. In addition, patients displaying eye phenotypes in the absence of extraocular manifestations should be analyzed first for exon 2 mutations. Linkage analysis identified a new locus for autosomal recessive nonsyndromic hearing loss (DFNB32) on chromosome 1p13.3-22.1 in a Tunisian family with congenital profound autosomal recessive deafness. The COL11A1 gene is located in this region and was analyzed as a candidate gene. No disease causing sequence variation was observed. The analysis of 85 English and 40 Finnish subjects with high myopia resulted in the identification 23 sequence variations in the SLRP genes LUM, FMOD, PRELP, and OPTC. The two intronic variations and seven amino acid changes, one synonymous and six non-synonymous, were not found in the 308 controls analyzed. Five changes were detected in opticin, and all but one were shown to co-segregate with high myopia in families with incomplete penetrance. The results suggested that sequence variations in the SLRP genes expressed in the eye are genetic risk factors underlying the pathogenesis of high myopia.

Subjects/Keywords: Stickler syndrome; autosomal recessive nonsyndromic hearing loss; high myopia; predominantly ocular variant

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Majava, M. (. (2007). Molecular genetics of Stickler and Marshall syndromes, and the role of collagen II and other candidate proteins in high myopia and impaired hearing. (Doctoral Dissertation). University of Oulu. Retrieved from http://urn.fi/urn:isbn:9789514283628

Chicago Manual of Style (16^th Edition):

Majava, M (Marja). “Molecular genetics of Stickler and Marshall syndromes, and the role of collagen II and other candidate proteins in high myopia and impaired hearing.” 2007. Doctoral Dissertation, University of Oulu. Accessed March 08, 2021. http://urn.fi/urn:isbn:9789514283628.

MLA Handbook (7^th Edition):

Majava, M (Marja). “Molecular genetics of Stickler and Marshall syndromes, and the role of collagen II and other candidate proteins in high myopia and impaired hearing.” 2007. Web. 08 Mar 2021.

Vancouver:

Majava M(. Molecular genetics of Stickler and Marshall syndromes, and the role of collagen II and other candidate proteins in high myopia and impaired hearing. [Internet] [Doctoral dissertation]. University of Oulu; 2007. [cited 2021 Mar 08]. Available from: http://urn.fi/urn:isbn:9789514283628.

Council of Science Editors:

Majava M(. Molecular genetics of Stickler and Marshall syndromes, and the role of collagen II and other candidate proteins in high myopia and impaired hearing. [Doctoral Dissertation]. University of Oulu; 2007. Available from: http://urn.fi/urn:isbn:9789514283628

30. Ντάϊου, Χρύσα. Μαζικός γενετικός έλεγχος σε διαφορετικές ομάδες πληθυσμού στην ευρύτερη περιοχή της Θεσσαλίας με σκοπό την ανίχνευση του ποσοστού των φορέων της ασθένειας Friedreich's ataxia.

Degree: 2011, University of Thessaly (UTH); Πανεπιστήμιο Θεσσαλίας

URL: http://hdl.handle.net/10442/hedi/25027

►

Autosomal Recessive Cerebellar Ataxias (ARCA) encompass a large number of rare neurological disorders characterized by early onset, cerebellar ataxia and autosomal recessive inheritance. The commonest… (more)

▼

Autosomal Recessive Cerebellar Ataxias (ARCA) encompass a large number of rare neurological disorders characterized by early onset, cerebellar ataxia and autosomal recessive inheritance. The commonest ARCA is Friedreich ataxia (FRDA). Homozygosity for an abnormal GAA repeat expansion (98%) and compound heterozygosity for the expansion and a point mutation of the frataxin gene (2%) have been identified. Recently, another subgroup of ARCA associated with oculomotor apraxia (AOA) has been distinguished. Oculomotor apraxia I (AOA1) is caused by mutation of the aprataxin gene. Firstly, we studied the frequency of the FRDA mutation in Thessaly. We found that the frequency is similar with other European reports (1.22%). In the second part, we studied 14 patients with sporadic cerebellar ataxia. Analysis of the 14 patients for the FXN gene GAA expansion revealed that all but one had normal allele sizes. One of them was heterozygous for the expansion. Based on previous studies, these 14 patients were further examined for APTX gene mutations. In the third part, we further examined GAA expansion carrier for point mutation in the FXN gene using sequencing analysis for the FXN gene. This patient carried a single nucleotide polymorphism (refSNP ID: rs2481598). In conclusion, the present thesis studied the frequency of the FRDA mutation for the first time in Greece. Moreover, we investigated 14 patients with sporadic cerebellar ataxia at the APTX gene based on previous studies. Our results do not confirm the previous studies.

Οι ARCA είναι νευρολογικές παθήσεις, χαρακτηρίζονται από εκφυλισμό ή ανώμαλη ανάπτυξη της παρεγκεφαλίδας και του νωτιαίου μυελού, αυτοσωμική υπολειπόμενη κληρονόμηση και έναρξη <20 ετών. H αταξία του Friedreich (FRDA) είναι η συχνότερη ARCA. Η συχνότερη μετάλλαξη FRDA (98%) είναι η υπερεπέκταση των επαναλήψεων της τριπλέττας GAA του γονιδίου FXN. Το 2% των ασθενών με FRDA είναι ταυτόχρονα φορείς της επέκτασης των GAA και σημειακών μεταλλάξεων. Πρόσφατα, αναγνωρίσθηκε μια υποκατηγορία των ARCA οι οποίες σχετίζονται με οπτικοκινητική απραξία (ΑΟΑ). Μεταλλάξεις στο γονίδιο της απραταξίνης (APTX) προκαλούν οπτικοκινητική απραξία (ΑΟΑ1). Στην πρώτη φάση της διδακτορικής διατριβής μελετήθηκε η συχνότητα της συχνότερης μετάλλαξης FXN στον Ελλαδικό χώρο, η οποία ανέρχεται σε ποσοστό 1.22%. Επίσης, έγινε επιβεβαίωση των αποτελεσμάτων με την τεχνική της αλληλούχησης . Στη δεύτερη φάση μελετήθηκαν 14 ασθενείς με νωτιαιοπαρεγκεφαλιδική αταξία. Διερευνήθηκαν για τη μετάλλαξη του γονιδίου FXN. Δεκατρείς ασθενείς έφεραν φυσιολογικά αλληλόμορφα, ενώ ένας από αυτούς ήταν φορέας. Στη συνέχεια μελετήσαμε το γονίδιο APTX με την μέθοδο της αλληλούχησης. Δεν διαπιστώθηκαν μεταλλάξεις για το γονίδιο APTX. Στη τρίτη φάση, έγινε έλεγχος του γονιδίου FXN στον ασθενή που ήταν ετερόζυγος για την επέκταση GAA, ώστε να μελετηθεί η παρουσία σημειακών μεταλλάξεων. Η ανάλυση έγινε με την τεχνική της αλληλούχησης και κατέδειξε ένα γνωστό πολυμορφισμό (refSNP ID: rs2481598). Συνοπτικά, στη παρούσα διατριβή μελετήθηκε για πρώτη φορά στην…

Subjects/Keywords: Αυτοσωμική υπολειπόμενη κληρονόμηση; Μετάλλαξη; Τριπλέττα GAA; Οπτικοκινητική απραξία; Νωτιαιοπαρεγκεφαλιδική αταξία; Συχνότητα; Φορέας; Αλληλούχιση; Autosomal recessive inheritance; Mutation; GAA repeat; Oculomotor apraxia; Cerebellar ataxia; Frequency; Carrier; Sequencing analysis

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ντάϊου, . �. (2011). Μαζικός γενετικός έλεγχος σε διαφορετικές ομάδες πληθυσμού στην ευρύτερη περιοχή της Θεσσαλίας με σκοπό την ανίχνευση του ποσοστού των φορέων της ασθένειας Friedreich's ataxia. (Thesis). University of Thessaly (UTH); Πανεπιστήμιο Θεσσαλίας. Retrieved from http://hdl.handle.net/10442/hedi/25027

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Ντάϊου, Χρύσα. “Μαζικός γενετικός έλεγχος σε διαφορετικές ομάδες πληθυσμού στην ευρύτερη περιοχή της Θεσσαλίας με σκοπό την ανίχνευση του ποσοστού των φορέων της ασθένειας Friedreich's ataxia.” 2011. Thesis, University of Thessaly (UTH); Πανεπιστήμιο Θεσσαλίας. Accessed March 08, 2021. http://hdl.handle.net/10442/hedi/25027.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Ντάϊου, Χρύσα. “Μαζικός γενετικός έλεγχος σε διαφορετικές ομάδες πληθυσμού στην ευρύτερη περιοχή της Θεσσαλίας με σκοπό την ανίχνευση του ποσοστού των φορέων της ασθένειας Friedreich's ataxia.” 2011. Web. 08 Mar 2021.

Vancouver:

Ντάϊου �. Μαζικός γενετικός έλεγχος σε διαφορετικές ομάδες πληθυσμού στην ευρύτερη περιοχή της Θεσσαλίας με σκοπό την ανίχνευση του ποσοστού των φορέων της ασθένειας Friedreich's ataxia. [Internet] [Thesis]. University of Thessaly (UTH); Πανεπιστήμιο Θεσσαλίας; 2011. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/10442/hedi/25027.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Ντάϊου �. Μαζικός γενετικός έλεγχος σε διαφορετικές ομάδες πληθυσμού στην ευρύτερη περιοχή της Θεσσαλίας με σκοπό την ανίχνευση του ποσοστού των φορέων της ασθένειας Friedreich's ataxia. [Thesis]. University of Thessaly (UTH); Πανεπιστήμιο Θεσσαλίας; 2011. Available from: http://hdl.handle.net/10442/hedi/25027

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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Open Access Theses and Dissertations