MHC class IIa haplotypes derived by high-throughput SNP screening in an isolated sheep population.

MHC class IIa haplotypes derived by high-throughput SNP screening in an isolated sheep population.
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DOI:
10.1093/g3journal/jkab200
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发表时间:
2021-09-27
期刊:
G3 (Bethesda, Md.)
影响因子:
--
通讯作者:
Johnston SE
Johnston SE
中科院分区:
其他
文献类型:
--
作者:
Dicks KL;Pemberton JM;Ballingall KT;Johnston SE

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研究目前作用于高度多态性基因区域(如主要组织相容性复合体(MHC))的进化过程,需要大量的基因型和表型的人口数据。MHC由几个紧密连锁的基因座组成,具有等位基因和基因含量变异,使其对基因型具有挑战性。8 IIa类单倍型已被确定在Soay羊(Ovis aries)的圣基尔达使用桑格测序和克隆,但没有一个单一的基因座是代表所有的单倍型。在这里,我们利用封闭的性质的岛屿人口的Soay绵羊和其有限的单倍型变异,以确定一个面板的SNPs,使插补的MHC单倍型。我们比较了135个个体的基于桑格序列的基因分型确定的MHC IIa类单倍型与使用绵羊Infinium HD BeadChip生成的SNP谱。一组11个SNPs可以可靠地确定MHC双倍型,DQA 1基因内的两个额外的SNPs能够检测仅影响表达基因下游的SNPs的重组单倍型。对5951只Soay羊进行了13个SNPs的基因分型,其中5349只通过了质量控制。使用Soay绵羊系谱,我们能够追踪重组SNP单倍型的起源和遗传。这种基于SNP的方法使大量Soay羊的基因座特异性MHC基因型的快速生成成为可能。这一数量的高品质的基因型在一个良好的特点人口的自由生活的绵羊将是有价值的调查机制保持多样性的MHC。
Investigating the current evolutionary processes acting on a highly polymorphic gene region, such as the major histocompatibility complex (MHC), requires extensive population data for both genotypes and phenotypes. The MHC consists of several tightly linked loci with both allelic and gene content variation, making it challenging to genotype. Eight class IIa haplotypes have previously been identified in the Soay sheep (Ovis aries) of St. Kilda using Sanger sequencing and cloning, but no single locus is representative of all haplotypes. Here, we exploit the closed nature of the island population of Soay sheep and its limited haplotypic variation to identify a panel of SNPs that enable imputation of MHC haplotypes. We compared MHC class IIa haplotypes determined by Sanger sequence-based genotyping of 135 individuals to their SNP profiles generated using the Ovine Infinium HD BeadChip. A panel of 11 SNPs could reliably determine MHC diplotypes, and two additional SNPs within the DQA1 gene enabled detection of a recombinant haplotype affecting only the SNPs downstream of the expressed genes. The panel of 13 SNPs was genotyped in 5951 Soay sheep, of which 5349 passed quality control. Using the Soay sheep pedigree, we were able to trace the origin and inheritance of the recombinant SNP haplotype. This SNP-based method has enabled the rapid generation of locus-specific MHC genotypes for large numbers of Soay sheep. This volume of high-quality genotypes in a well-characterized population of free-living sheep will be valuable for investigating the mechanisms maintaining diversity at the MHC.
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