Genetic and Molecular Characterization of SCA26

SCA26 的遗传和分子特征

• 批准号: 7255072
• 负责人: Christopher Manuel Gomez
• 金额: $ 7.67万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-15 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7255072
• 关键词: Friedreich' s ataxia; ataxia; cerebellum; cerebral degeneration; clinical research; diagnosis design /evaluation; diagnostic tests; family genetics; gene mutation; genetic mapping; genetic screening; genotype; human genetic material tag; human subject; molecular biology information system; molecular pathology; neural degeneration; neurons; nucleic acid sequence; pathologic process; patient oriented research

DESCRIPTION (provided by applicant): The autosomal dominant spinocerebellar ataxias (SCA) are a clinically and genetically heterogeneous group of neurodegenerative diseases. It is clear that a diverse of genes and mutational mechanisms can cause SCA, but the molecular process and mechanism for Purkinje cell degeneration that leads to SCA is still unknown. Further insights into SCA pathogenesis may come from more studies that have demonstrated that not all SCAs are due to expanded DNA repeats in novel genes. We recently identified a large family with a novel dominant ataxia, register as SCA26, and mapped the disease locus to 19p13.3. The long-range goal of this research is to expand our understanding of the pathogenesis of the hereditary ataxias, and specifically the basis for the nearly selective Purkinje cell degeneration. We hypothesize that SCA26 is caused by a mutation in a gene that is vital to neuron survival or specific function in the cerebellum, and have identified a few compelling candidate genes. The objective of this project is to refine the locus map by recruiting more family members, and by seeking a different founder haplotype from unrelated families, and to identify the gene and mutational basis by sequencing all coding regions of top candidate genes, and to survey the prevalence of SCA26. This project is significant because: 1) it will directly benefit ataxic patients by providing a new genetic test for diagnosis and genetic consulting; 2) it will provide a new model to study Purkinje cell and cerebellar degeneration in ataxia patients; 3) more broadly, it will establish a new point to inter-connect known factors together, and unveil new insights to delineate the common pathways involved in neurodegeneration or vital to neuron survival and function.

描述(由申请人提供)： 常染色体显性遗传性脊髓小脑性共济失调(SCA)是一组临床和遗传异质性的神经退行性疾病。很明显，多种基因和突变机制可导致SCA，但导致SCA的浦肯野细胞退变的分子过程和机制尚不清楚。对SCA发病机制的进一步了解可能来自更多的研究，这些研究证明并不是所有的SCA都是由于新基因中扩大的DNA重复所致。我们最近发现了一个新的显性共济失调大家族，注册为SCA26，并将该疾病基因定位在19p13.3。这项研究的长期目标是扩大我们对遗传性共济失调发病机制的理解，特别是为几乎选择性的浦肯野细胞变性奠定基础。我们假设SCA26是由一个基因突变引起的，该基因对小脑中的神经元生存或特定功能至关重要，并已确定了一些引人注目的候选基因。本项目的目的是通过招募更多的家庭成员来完善基因座图谱，通过从不相关的家系中寻找不同的创始人单倍型，并通过对顶级候选基因的所有编码区进行测序来确定基因和突变基础，并调查SCA26的患病率。该项目具有重大意义，因为：1)它将为诊断和遗传咨询提供一种新的基因测试，从而直接造福于共济失调患者；2)它将为研究共济失调患者的浦肯野细胞和小脑变性提供一个新的模型；3)更广泛地说，它将建立一个新的点，将已知的因素联系在一起，并揭示新的见解，以描绘参与神经变性或对神经元生存和功能至关重要的常见通路。