A highly divergent microsatellite facilitating fast and accurateDRBhaplotyping in humans and rhesus macaques

Abstract

The DRB region of the MHC in primate species is known to display abundant region configuration polymorphism with regard to the number and content of genes present per haplotype. Furthermore, depending on the species studied, the different DRB genes themselves may display varying degrees of allelic polymorphism. Because of this combination of diversity (differential gene number) and polymorphism (allelic variation), molecular typing methods for the primate DRB region are cumbersome. All intact DRB genes present in humans and rhesus macaques appear to possess, however, a complex and highly divergent microsatellite. Microsatellite analysis of a sizeable panel of outbred rhesus macaques, covering most of the known Mamu-DRB haplotypes, resulted in the definition of unique genotyping patterns that appear to be specific for a given haplotype. Subsequent examination of a representative panel of human cells illustrated that this approach also facilitates high-resolution HLA-DRB typing in an easy, quick, and reproducible fashion. The genetic composition of this complex microsatellite is shown to be in concordance with the phylogenetic relationships of various HLA-DRB and Mamu-DRB exon 2 gene/lineage sequences. Moreover, its length variability segregates with allelic variation of the respective gene. This simple protocol may find application in a variety of research avenues such as transplantation biology, disease association studies, molecular ecology, paternity testing, and forensic medicine.biological science ͉ MHC

Study of cynomolgus monkey (Macaca fascicularis) Mhc DRB gene polymorphism in four populations

“…On the other hand, among the 30 DRB haplotypes described in the rhesus monkey (Doxiadis et al 2007), 9 are similar to those described in Mafa (this study and Doxiadis et al 2010Doxiadis et al , 2012 (Table 7 in the ESM). The persistence of these haplotypes over time in different populations of rhesus and cynomolgus macaques could have been favored by selection.…”

The hidden benefits of sex: Evidence for MHC‐associated mate choice in primate societies

“…The next generation sequencing technologies will help to overcome these difficulties, allowing large-scale genotyping [79]. Advances in nonhuman primate genomics will allow us to design new genotyping tools that span larger MHC regions, and may even allow the identification of microsatellite and single nucleotide polymorphisms across the MHC region, which will facilitate MHC typing [83] from non-invasive samples and allow us to identify exactly which genes are important in mate choice.…”

Microsatellite-based genotyping of MHC class II DRB1 gene in Iberian and Alpine ibex

“…This microsatellite is located at the beginning of intron 2 and has a compound character (Trtkova et al 1995;Bergstrom et al 1999;Kriener et al 2000). In humans and Rhesus macaques, genotyping of large samples resulted in the definition of DRB-STR patterns that were characteristic for a certain haplotype (Doxiadis et al 2007). Associations between polymorphisms in an intronic microsatellite and the coding sequences for class II MHC genes were also reported in bovids (e.g., Sigurdardottir et al 1991;Ellegren et al 1993) and domestic and wild sheep (Schwaiger et al 1993;Outteridge et al 1996;Paterson 1998).…”

“…A complex microsatellite repeat, designated DRB-STR, located in close proximity to DRB exon 2 is present in many mammalian species, including humans and primates (Andersson et al 1987;Doxiadis et al 2007). This microsatellite is located at the beginning of intron 2 and has a compound character (Trtkova et al 1995;Bergstrom et al 1999;Kriener et al 2000).…”