Immunogenetic Studies in Multiple Sclerosis

描述（由申请人提供）：多发性硬化症（MS）是一种常见的中枢神经系统炎症性疾病，其病因复杂，包括强烈的遗传成分。我们的目标是整合现代统计和分子基因组方法，以确定这种疾病的易感性和修饰性基因组决定因素。基于MS包含不止一种基本表型的假设，以及基因组失衡模式是由种群历史形成的理解，我们提出了对比种族群体的研究，以确定早期重组事件和包含疾病基因的最小基因组区域。

DESCRIPTION (provided by applicant): Multiple sclerosis (MS) is a common inflammatory disorder of the central nervous system characterized by a complex etiology that includes a strong genetic component. Our goal is to integrate modern statistical and molecular genomic methods to identify susceptibility and modifier genomic determinants in this disease. Based on the hypothesis that MS encompasses more than one basic phenotype, and the understanding that patterns of genomic dysequilibrium are shaped by the population history, we propose the study of contrasting ethnic groups to identify early recombination events and minimal genomic regions harboring disease genes. We will use rigorous clinical criteria to ascertain 1000 MS patients of African-American descent. Specific Aim 1 describes a whole genome association screen of medium resolution (approximately 6,000 microsatellite markers) using a highly effective DNA pooling approach. Specific Aim 2 is primarily concerned with the detailed analysis of the candidate chromosomal regions 6p21 and 19q13. In Specific Aim 3, promising candidate genes will be directly tested for mutations and informative polymorphisms associated with disease susceptibility. Clinical and paraclinical variables will be stratified by genotypes to address the question of heterogeneity in MS and the correlation between different phenotypes and genotypes. Key to the success of these studies will be the acquisition of a large and informative dataset, together with the standardization of rigorous and consistent methods to collect relevant clinical data, and availability of efficient genotyping methods, adequate bioinformatic tools, and innovative analytical strategies.