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 ∼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.
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We thank Ann Eldridge, Marlene Grace and Anjali Henders for assistance and the twins, their siblings and their parents for their cooperation. Collection of phenotypes and DNA samples was supported by grants from the Queensland Cancer Fund, the Australian National Health and Medical Research Council (950998, 981339 and 241944) and the US National Cancer Institute (CA88363) to Dr Nick Hayward. The genome scans were supported by the Australian NHMRC's Program in Medical Genomics and funding from the Center for Inherited Disease Research (Director, Dr Jerry Roberts) at Johns Hopkins University to Dr Jeff Trent.
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Evans, D., Zhu, G., Duffy, D. et al. A major quantitative trait locus for CD4–CD8 ratio is located on chromosome 11. Genes Immun 5, 548–552 (2004). https://doi.org/10.1038/sj.gene.6364126
- CD4–CD8 ratio
- genetic mapping
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