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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS046297-02
Application #
6777558
Study Section
Immunological Sciences Study Section (IMS)
Program Officer
Utz, Ursula
Project Start
2003-07-16
Project End
2007-04-30
Budget Start
2004-05-01
Budget End
2005-04-30
Support Year
2
Fiscal Year
2004
Total Cost
$347,581
Indirect Cost
Name
University of California San Francisco
Department
Neurology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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