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CHARACTERIZATION OF KIR3DL1/3DS1 SUBTYPES.
Xiaojiang Gao PhD , Darlene Marti , Pete Karacki , Pat Martin MD and Mary Canrrington PhD . Frederick MD, SAIC-Frederick, NCI, 21702, Laboratory of Genomic Diversity .

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The gene locus encoding both KIR3DL1 and KIR3DS1 is one of the most polymorphic KIR genes with more than twenty 3DL1 and five 3DS1 alleles reported so far. Very little is known about the population distribution of these KIR subtypes and their involvement in disease associations. In the present study we developed a SSO-based typing protocol to characterize KIR3DL1/3DS1 subtypes and investigate their distribution in Caucasians (N=1558) and African Americans (N=581). Four sets of locus-specific primers were used to amplify exon 3, exon4, exon 5 and exons 7 through 9 respectively. PCR products were hybridized with a panel of 50 SSO probes to detect all known polymorphic nucleotide epitopes in these exons. A total of 13 KIR3DL1 and one KIR3DS1 alleles were detected. Three of the detected KIR3DL1 alleles showed unexpected SSO patterns and were confirmed by sequencing analysis as previously unreported novel alleles. Caucasians and African Americans showed markedly different distributions of the KIR subtypes. The frequencies of KIR3DL1 vs. KIR3DS1 are 80% vs. 20% in Caucasians and 94.3% vs. 5.7% in African Americans respectively. Common KIR3DL1 subtypes (gf > 10%) include KIR3DL1*001, 002, 00402, and 005 in Caucasians and KIR3DL1*003, 00402, and N1 in African Americans. The three novel alleles were all detected exclusively in African Americans and they collectively account for 33.6% of the gene frequency in this population. The markedly different population distributions of KIR3DL1/3DS1 subtypes indicates that KIR genes has been through rapid diversification and the KIR subtypes might have been under selection due to functional significance in KIR mediated NK cytotoxicity. This work was supported with federal funds from the National Cancer Institute, National Institutes of Health under contract No. NO1-CO-12400.