A major quantitative trait locus for CD4-CD8 ratio is located on chromosome 11.
CD4-CD8 ratio is an important diagnostic measure of immune system functioning. In particular, CD4-CD8 ratio predicts the time taken for progression of HIV infection to acquired immune deficiency syndrome (AIDS) and the long-term survival of AIDS patients. To map genes that regulate differences between healthy individuals in CD4-CD8 ratio, we typed 757 highly polymorphic microsatellite markers at an average spacing of approximately 5 cM across the genome in 405 pairs of dizygotic twins at ages 12, 14 and 16. We used multipoint variance components linkage analysis to test for linkage between marker loci and CD4-CD8 ratio at each age. We found suggestive evidence of linkage on chromosome 11p in 12-year-old twins (LOD=2.55, P=0.00031) and even stronger evidence of linkage in the same region at age 14 (LOD=3.51, P=0.00003). Possible candidate genes include CD5 and CD6, which encode cell membrane proteins involved in the positive selection of thymocytes. We also found suggestive evidence of linkage at other areas of the genome including regions on chromosomes 1, 3, 4, 5, 6, 12, 13, 15, 17 and 22.
Queensland Institute of Medical Research, Brisbane, Australia. davide@well.ox.ac.uk
D M
DM
Evans
G
G
Zhu
D L
DL
Duffy
I H
IH
Frazer
G W
GW
Montgomery
N G
NG
Martin
D000293:Adolescent; D016516:CD4-CD8 Ratio / Q000706:statistics & numerical data; D016009:Chi-Square Distribution; D002648:Child; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D005260:Female; D006801:Humans; D008126:Lod Score; D008297:Male; D040641:Quantitative Trait Loci / Q000235:genetics*; D014429:Twins, Dizygotic / Q000235:genetics