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）： 常染色体显性脊椎发子（SCA）是临床和遗传异质性疾病的一组。显然，多种基因和突变机制可能导致SCA，但是导致SCA的Purkinje细胞变性的分子过程和机制仍然未知。对SCA发病机理的进一步见解可能来自更多的研究，这些研究表明，并非所有SCA都是由于新基因中的DNA重复量扩大而引起的。我们最近确定了一个具有新型共济失调的大家庭，注册为SCA26，并将疾病基因座映射到19p13.3。这项研究的远距离目标是扩展我们对遗传性行为的发病机理的理解，尤其是近乎选择性的Purkinje细胞变性的基础。我们假设SCA26是由基因中的突变引起的，该突变对神经元的存活或小脑中的特定功能至关重要，并且已经鉴定出一些引人注目的候选基因。该项目的目的是通过招募更多的家庭成员，并从无关家族中寻求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域进行测序，并调查SCA26的流行，并确定基因和突变基础。该项目很重要，因为：1）通过为诊断和遗传咨询提供新的基因检测，它将直接受益于共同患者； 2）它将提供一种新的模型来研究共济失调患者的Purkinje细胞和小脑变性； 3）更广泛地，它将建立一个新点，以共同连接已知因素，并提出新的见解，以描绘与神经变性或对神经元的生存和功能至关重要的共同途径。