Inheritance pattern of mutant human immunodeficiency virus type 1 coreceptor gene CCR5 in an Indian family

The most common form of mutation found in the CCR5 gene has been the precise 32-base pair (bp) deletion in the region corresponding to second extracellular loop of the chemokine receptor CCR5. Individuals homozygous for the delta 32 allele of CCR5 usually remain uninfected despite multiple exposures to HIV, whereas heterozygous individuals support less virus replication and show slower progression of the disease. This mutant allele in either homozygous or heterozygous form is quite common in white people of European heritage. Earlier work involving large populations of Asians and Africans failed to detect the presence of this mutant allele. We screened 145 normal unrelated healthy Indians and found one person who was heterozygous for the delta 32 allele of CCR5. We studied the inheritance of this deleted allele in this person's family. One parent, one of two sons, and the only daughter possessed this mutant allele. We cloned the entire coding region of wild-type and mutant alleles of CCR5 gene from the heterozygous individual mentioned and studied its coreceptor functions. The mutant allele had only a moderate interfering effect on coreceptor activity of the wild-type CCR5 allele in a cell fusion assay. We also report an improved method of genotyping CCR5 gene in this communication.