Linkage disequilibrium organization of the human KIR superlocus: implications for KIR data analyses

An extensive family-based study of linkage disequilibrium (LD) in the killer cell immunoglobulin-like receptors (KIR) cluster was performed. We aimed to describe the LD structure in the KIR gene cluster using a sample of 418 founder haplotypes identified by segregation in a group of 106 families from Northern Ireland. The LD was studied at two levels of polymorphism: the structural level (presence or absence of KIR genes) and the allelic level (between alleles of KIR genes). LD was further assessed using the predictive value of one KIR polymorphism for another one in order to provide an interpretative framework for the LD effect in association studies. In line with previous research, distinct patterns of KIR genetic diversity within the genomic region centromeric to KIR2DL4 (excluding KIR2DL4) and within the telomeric region including KIR2DL4 were found. In a comprehensive PPV/NPV-based LD analysis within the KIR cluster, robust tag markers were found that can be used to identify which genes are concomitantly present or absent and to further identify groups of associated KIR alleles. Several extended KIR haplotypes in the study population were identified (KIR2DS2*POS–KIR2DL2*001–KIR2DL5B*002–KIR2DS3*00103–KIR2DL1*00401; KIR2DL4*011–KIR3DL1/S1*005–KIR2DS4*003–KIR3DL2*003; KIR2DL4*00802–KIR3DL1/S1*004–KIR2DS4*006–KIR3DL2*005; KIR2DL4*00801–KIR3DL1/S1*00101–KIR2DS4*003–KIR3DL2*001; KIR2DL4*00103–KIR3DL1/S1*008–KIR2DS4*003–KIR3DL2*009; KIR2DL4*00102–KIR3DL1/S1*01502/*002–KIR2DS4*00101–KIR3DL2*002; KIR2DL4*00501–KIR3DL1/S1*013–KIR2DL5A*001–KIR2DS5*002–KIR2DS1*002–KIR3DL2*007). The present study provides a rationale for analyzing associations of KIR polymorphisms by taking into account the complex LD structure of the KIR region

Distinct diversity of KIR genes in three Southern Indian populations: comparison with world populations revealed a link between KIR gene content and pre-historic human migrations

By interacting with polymorphic HLA class I molecules, the killer cell immunoglobulin-like receptors (KIR) influence the innate and adaptive immune response to infection. The KIR family varies in gene content and sequence polymorphism, thereby, distinguishing individuals and populations. To investigate KIR diversity in the earliest settlers of India, we have characterized the KIR gene content in three Dravidian-speaking populations (Mollukurumba, Kanikar, and Paravar) from the state of Tamil Nadu, southern India. The activating KIR genes and putative group-B KIR haplotypes were frequent in Paravar and Kanikar, a scenario analogous to those seen previously in other populations of Indian origin, indicating that predominance of group-B KIR haplotypes is the characteristic feature of Indian populations. In contrast, the KIR gene profile of Mollukurumba was more related to Caucasian type. It is not clear whether a local-specific selection or a recent admixture from Iran is responsible for such discrete profile in Mollukurumba. Each southern Indian population had distinct KIR genotype profile. Comparative analyses with world populations revealed that group-B KIR haplotypes were frequent in the natives of India, Australia, and America, the populations associated with those involved in extensive prehistoric human migrations. Whether or not natural selection has acted to enrich group-B KIR haplotypes in these migratory descendants is an issue that requires objective testing