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KIR genotypic diversity can track ancestries in heterogeneous populations: a potential confounder for disease association studies.

ABSTRACT: Killer cell immunoglobulin-like receptors (KIR) are encoded by highly polymorphic genes that regulate the activation of natural killer (NK) cells and other lymphocyte subsets and likely play key roles in innate and adaptive immunity. Association studies increasingly implicate KIR in disease predisposition and outcome but could be confounded by unknown KIR genetic structure in heterogeneous populations. To examine this, we characterized the diversity of 16 KIR genes in 712 Northern Californians (NC) stratified by self-assigned ethnicities and compared the profiles of KIR polymorphism with other US and global populations using a reference database. Sixty-eight distinct KIR genotypes were characterized: 58 in 457 Caucasians (NCC), 17 in 47 African Americans (NCAA), 21 in 80 Asians (NCA), 20 in 74 Hispanics (NCH), and 18 in 54 "other" ethnicities (NCO). KIR genotype patterns and frequencies in the 4 defined ethnicities were compared with each other and with 34 global populations by phylogenetic analysis. Although there were no population-specific genotypes, the KIR genotype frequency patterns faithfully traced the ancestry of NCC, NCAA, and NCA but not of NCH whose ancestries are known to be more heterogeneous. KIR genotype frequencies can therefore track ethnic ancestries in modern urban populations. Our data emphasize the importance of selecting ethnically matched controls in KIR-based studies to avert spurious associations.

SUBMITTER: Singh KM

PROVIDER: S-EPMC4143378 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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KIR genotypic diversity can track ancestries in heterogeneous populations: a potential confounder for disease association studies.

Singh Komal Manpreet KM Phung Yume T YT Kohla Mohamed S MS Lan Billy Y-A BY Chan Sharon S Suen Diana L DL Murad Sahar S Rheault Shana S Davidson Peter P Evans Jennifer J Singh Manpreet M Dohil Sofie S Osorio Robert W RW Wakil Adil E AE Page Kimberly K Feng Sandy S Cooper Stewart L SL

Immunogenetics 20110907 2

Killer cell immunoglobulin-like receptors (KIR) are encoded by highly polymorphic genes that regulate the activation of natural killer (NK) cells and other lymphocyte subsets and likely play key roles in innate and adaptive immunity. Association studies increasingly implicate KIR in disease predisposition and outcome but could be confounded by unknown KIR genetic structure in heterogeneous populations. To examine this, we characterized the diversity of 16 KIR genes in 712 Northern Californians ( ...[more]

PMID: 21898189

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Project description:Ascochyta fabae Speg. is a serious foliar fungal disease of faba bean and a constraint to production worldwide. This study investigated the phenotypic and genotypic diversity of the A. fabae pathogen population in southern Australia and the pathogenic variability of the population was examined on a differential set of faba bean cultivars. The host set was inoculated with 154 A. fabae isolates collected from 2015 to 2018 and a range of disease reactions from high to low aggressiveness was observed. Eighty percent of isolates collected from 2015 to 2018 were categorized as pathogenicity group (PG) PG-2 (pathogenic on Farah) and were detected in every region in each year of collection. Four percent of isolates were non-pathogenic on Farah and designated as PG-1. A small group of isolates (16%) were pathogenic on the most resistant differential cultivars, PBA Samira or Nura, and these isolates were designated PG-3. Mating types of 311 isolates collected between 1991 and 2018 were determined and showed an equal ratio of MAT1-1 and MAT1-2 in the southern Australian population. The genetic diversity and population structure of 305 isolates were examined using DArTseq genotyping, and results suggest no association of genotype with any of the population descriptors viz.: collection year, region, host cultivar, mating type, or PG. A Genome-Wide Association Study (GWAS) was performed to assess genetic association with pathogenicity traits and a significant trait-associated genomic locus for disease in Farah AR and PBA Zahra, and PG was revealed. The high frequency of mating of A. fabae indicated by the wide distribution of the two mating types means changes to virulence genes would be quickly distributed to other genotypes. Continued monitoring of the A. fabae pathogen population through pathogenicity testing will be important to identify any increases in aggressiveness or emergence of novel PGs. GWAS and future genetic studies using biparental mating populations could be useful for identifying virulence genes responsible for the observed changes in pathogenicity.

Dataset Information

KIR genotypic diversity can track ancestries in heterogeneous populations: a potential confounder for disease association studies.

Publications

KIR genotypic diversity can track ancestries in heterogeneous populations: a potential confounder for disease association studies.

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