Thirty allele-level haplotypes centered around KIR2DL5 define the diversity in an African American population

Abstract

KIR2DL5 alleles were physically linked to alleles at adjacent KIR loci to define this region of KIR haplotypes in 55 gene positive random African Americans. The majority carried KIR2DL5B. Three KIR2DL5A and six KIR2DL5B alleles that have been previously described and 11 novel KIR2DL5 alleles were identified by DNA sequencing. Novel alleles included variation that may impact promoter activity; two alleles carried nonsynonymous coding region variation. Based on linkage with KIR2DS1, KIR2DS3, KIR2DS5, KIR2DL2, KIR2DL3, and KIR3DS1 alleles, 7 haplotypes of KIR2DL5A and 23 haplotypes of KIR2DL5B were observed. The phylogenetic relationships among the KIR2DL5 alleles predicted their association with either KIR2DS3 (6 alleles) or KIR2DS5 (7 alleles). All of the KIR2DL5A alleles were linked either to KIR3DS1*01301 or KIR3DS1*049N. The majority of the KIR2DL5B alleles were linked to seven KIR2DL2 alleles; two were linked to a novel allele of KIR2DL3. These findings underscore the diversity of KIR haplotypes present in this population.

Identification of four novel KIR2DL2 alleles and two novel KIR2DL3 alleles in an East African population

“…a This allele confirms the sequence reported by Hou et al, GenBank accession number EU933932[16]. b This allele confirms the sequence reported by Hou et al, GenBank accession number EU933933[16].…”

“…2DL2*00601 was identified in 19 of 957 individuals in this population and is a relatively common allele. This sequence was submitted to the World Health Organization (WHO) Nomenclature Committee for naming at approximately the same time by another group [16]. 1 The name listed for this sequence has been officially assigned by the KIR Nomenclature Committee.…”

“…2DL2*00602 was identified in 62 of 957 individuals in this population and represents a relatively common allele. This sequence was submitted to WHO Nomenclature Committee for naming at approximately the same time by another group [16].…”

Polymorphic HLA-C Receptors Balance the Functional Characteristics of KIR Haplotypes

“…The amino-acid substitutions that distinguish representative members of the four clades are shown in Figure 1B. Clade 1 comprises ten KIR2DL1*001 -like alleles (Figure 1B), seven of which have been mapped to KIR haplotypes (29, 38-43). Five of the seven are present in Cen A , the centromeric region of KIR A haplotypes (Figure 2).…”

“…To determine the basis for the weaker C2 avidity of Cen B encoded KIR2DL1, we compared KIR2DL1*003 and KIR2DL1*004 , respectively the most common Cen A and Cen B associated alleles (29, 38-41). In the D1 and D2 domains that form the ligand-binding site, KIR2DL1*003 and KIR2DL1*004 differ only in D2, at positions 114, 154, 163 and 182 (Figure 5A).…”