Genomic profiling of interpopulation diversity guides prioritization of candidate-genes for autoimmunity

Details

Serval ID
serval:BIB_E5D3126449A6
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Genomic profiling of interpopulation diversity guides prioritization of candidate-genes for autoimmunity
Journal
Genes Immun
Author(s)
Grossman  I., Avidan  N., Singer  C., Paperna  T., Lancet  D., Beckmann  J. S., Miller  A.
ISSN
1466-4879 (Print)
Publication state
Published
Issued date
09/2004
Volume
5
Number
6
Pages
493-504
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Sep
Abstract
Autoimmune diseases seem to have strong genetic attributes, and are affected to some extent by shared susceptibility loci. The latter potentially amount to hundreds of candidate genes (CG), creating the need for a prioritization strategy in genetic association studies. To form such a strategy, 26 autoimmune-related CG were genotyped for a total of 72 single nucleotide polymorphisms (SNPs) in three distinct Israeli ethnic populations: Ashkenazi Jews, Sephardic Jews and Arabs. Four quantitative criteria reflecting population stratification were analyzed: allele frequencies, haplotype frequencies, the Fst statistic for homozygotes distribution and linkage disequilibrium extents. According to the consequent interpopulation genomic diversity profiles, the genes were classified into conserved, intermediate and diversified gene groups. Our results demonstrate a correlation between the biological role of autoimmune-related CG and their interpopulation diversity profiles as classified by the different analyses. Annotation analysis suggests that genes more readily influenced by environmental conditions, such as immunological mediators, are 'population specific'. Conversely, genes showing genetic conservation across all populations are characterized by apoptotic and cleaving functions. We suggest a research strategy by which CG association studies should focus first on likely conserved gene categories, to increase the likelihood of attaining significant results and promote the development of gene-based therapies.
Keywords
Adult Arabs/*genetics Autoimmunity/*genetics Conserved Sequence Ethnic Groups/genetics Gene Frequency Genetic Predisposition to Disease/genetics *Genome, Human Genotype Haplotypes/genetics Homozygote Humans Jews/*genetics Linkage Disequilibrium Pilot Projects Polymorphism, Single Nucleotide/*genetics *Variation (Genetics)
Pubmed
Web of science
Open Access
Yes
Create date
25/01/2008 16:18
Last modification date
20/08/2019 16:09
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