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Use of Genome-wide Heterospecific Single-Nucleotide Polymorphisms to Estimate Linkage Disequilibrium in Rhesus and Cynomolgus Macaques

机译:全基因组异种单核苷酸多态性的使用,以估计恒河猴和食蟹猕猴的连锁不平衡。

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Rhesus and cynomolgus macaques are frequently used in biomedical research, and the availability of their reference genomes now provides for their use in genome-wide association studies. However, little is known about linkage disequilibrium (LD) in their genomes, which can affect the design and success of such studies. Here we studied LD by using 1781 conserved single-nucleotide polymorphisms (SNPs) in 183 rhesus macaques (Macacamulatta), including 97 purebred Chinese and 86 purebred Indian animals, and 96 cynomolgus macaques (M. fascicularis fascicularis). Correlation between loci pairs decayed to 0.02 at 1146.83, 2197.92, and 3955.83 kb for Chinese rhesus, Indian rhesus, and cynomolgus macaques, respectively. Differences between the observed heterozygosity and minor allele frequency (MAF) of pairs of these 3 taxa were highly statistically significant. These 3 nonhuman primate taxa have significantly different genetic diversities (heterozygosity and MAF) and rates of LD decay. Our study confirms a much lower rate of LD decay in Indian than in Chinese rhesus macaques relative to that previously reported. In contrast, the especially low rate of LD decay in cynomolgus macaques suggests the particular usefulness of this species in genome-wide association studies. Although conserved markers, such as those used here, are required for valid LD comparisons among taxa, LD can be assessed with less bias by using species-specific markers, because conserved SNPs may be ancestral and therefore not informative for LD.
机译:恒河猴和食蟹猕猴经常用于生物医学研究中,其参考基因组的可用性为它们在全基因组关联研究中的应用提供了条件。但是,人们对其基因组中的连锁不平衡(LD)知之甚少,这会影响此类研究的设计和成功。在这里,我们通过在183只猕猴(Macacamulatta)中使用1781个保守的单核苷酸多态性(SNP)来研究LD,其中包括97只中国纯种和86只印度纯种动物以及96只食蟹猕猴(M. fascicularis fascicularis)。中国恒河猴,印度恒河猴和食蟹猕猴的基因座对之间的相关性分别以1146.83、2199.72和3955.83 kb衰减至0.02。这三个类群对的观察到的杂合性和次要等位基因频率(MAF)之间的差异在统计学上具有高度统计学意义。这3个非人类的灵长类动物分类群具有显着不同的遗传多样性(杂合性和MAF)和LD衰减率。我们的研究证实,相对于先前报道的印度恒河猴而言,印度的LD衰减率要低得多。相反,食蟹猕猴的LD衰变率特别低,表明该物种在全基因组关联研究中特别有用。尽管在分类群之间进行有效的LD比较需要使用保守的标记(例如此处使用的标记),但是可以使用物种特异性标记以较小的偏倚来评估LD,因为保守的SNP可能是祖先的,因此对LD的信息不足。

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