Co-localization of differentially expressed genes and shared susceptibility loci in human autoimmunity.
Autoimmune diseases arise from complex interactions between environmental and genetic factors. Genetic linkage scans show that different autoimmune diseases share overlapping susceptibility loci. Lymphocytes from individuals with different autoimmune diseases, as well as unaffected first-degree relatives, also share a common gene expression profile. We sought to determine if genes within this autoimmune expression profile were nonrandomly distributed in the genome and if their distribution overlapped with shared disease susceptibility loci. We found that differentially expressed genes were distributed in a nonrandom fashion in chromosomal domains within the genome. Furthermore, positions of these domains were not statistically different from a number of shared autoimmune disease susceptibility loci. To our knowledge, this is the first study showing concordance between gene expression and genetic linkage results in common complex multifactorial human diseases.
Division of Rheumatology, Department of Medicine, Vanderbilt University Medical School, Nashville, Tennessee 37232, USA. thomas.aune@vanderbilt.edu
Thomas M
TM
Aune
Joel S
JS
Parker
Kevin
K
Maas
Zheng
Z
Liu
Nancy J
NJ
Olsen
Jason H
JH
Moore
D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000235:genetics*; D015551:Autoimmunity / Q000235:genetics; D002874:Chromosome Mapping / Q000379:methods*; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D020869:Gene Expression Profiling; D008040:Genetic Linkage / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged