Identification of polymorphic inversions from genotypes.
Identification of polymorphic inversions from genotypes.
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DOI：
10.1186/1471-2105-13-28
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发表时间：
2012-02-09
影响因子：
3
通讯作者：
González JR
中科院分区：
文献类型：
--
作者：
Cáceres A;Sindi SS;Raphael BJ;Cáceres M;González JR
多态倒位是遗传变异的一个来源，对重组频率有直接影响。考虑到它们实验研究的困难，已经开发出计算方法，利用全基因组核苷酸变异数据来推断它们在大量个体中的存在。基于已知倒位的单倍型标记的方法试图将个体分类为具有正常或倒置的等位基因。其他测量连锁不平衡差异的方法试图识别有倒位的区域，但无法准确地对受试者进行分类，这是关联研究的基本要求。我们提出了一种新的方法，既可以从全基因组的基因数据中识别多态倒置，又可以将个体分类为包含正常或倒置等位基因的个体。我们的方法是对已发表的单倍型数据方法的推广，利用SNPs组之间的链接将一组个体划分为正常和反转的亚群。我们使用滑动窗口扫描来识别可能发生倒位的区域，并使用来自邻近SNPs的证据积累来准确地确定每个受试者的倒位状态。此外，我们的方法直接从基因数据中检测到倒置，从而增加了它对当前全基因组关联研究(GWAS)的可用性。我们证明了我们的方法的准确性，以检测倒置和对个体分类的原则模拟的基因型，产生的反转事件在合并模型内的演变。我们将我们的方法应用于来自HapMap III阶段的真实基因数据，以表征1184个个体中17q21和8p23区域内两个已知倒位的倒置状态。最后，我们扫描了欧洲起源(CEU)和约鲁巴(YRI)HapMap样本的全基因组。我们发现了15个已确立的常染色体倒置中的9个基于群体的证据，以及之前通过独立实验方法在10个(9+1)个体中预测的52个区域的证据。我们提供了作为一个统一的R包反转的基因型和单倍型方法的有效实现。
Polymorphic inversions are a source of genetic variability with a direct impact on recombination frequencies. Given the difficulty of their experimental study, computational methods have been developed to infer their existence in a large number of individuals using genome-wide data of nucleotide variation. Methods based on haplotype tagging of known inversions attempt to classify individuals as having a normal or inverted allele. Other methods that measure differences between linkage disequilibrium attempt to identify regions with inversions but unable to classify subjects accurately, an essential requirement for association studies. We present a novel method to both identify polymorphic inversions from genome-wide genotype data and classify individuals as containing a normal or inverted allele. Our method, a generalization of a published method for haplotype data, utilizes linkage between groups of SNPs to partition a set of individuals into normal and inverted subpopulations. We employ a sliding window scan to identify regions likely to have an inversion, and accumulation of evidence from neighboring SNPs is used to accurately determine the inversion status of each subject. Further, our approach detects inversions directly from genotype data, thus increasing its usability to current genome-wide association studies (GWAS). We demonstrate the accuracy of our method to detect inversions and classify individuals on principled-simulated genotypes, produced by the evolution of an inversion event within a coalescent model. We applied our method to real genotype data from HapMap Phase III to characterize the inversion status of two known inversions within the regions 17q21 and 8p23 across 1184 individuals. Finally, we scan the full genomes of the European Origin (CEU) and Yoruba (YRI) HapMap samples. We find population-based evidence for 9 out of 15 well-established autosomic inversions, and for 52 regions previously predicted by independent experimental methods in ten (9+1) individuals. We provide efficient implementations of both genotype and haplotype methods as a unified R package inveRsion.
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影响因子：
4.5
作者：
Feuk L;MacDonald JR;Tang T;Carson AR;Li M;Rao G;Khaja R;Scherer SW
通讯作者：
Scherer SW
人类8p23.1反演多态性的核苷酸，细胞遗传学和表达影响。
影响因子：
3.7
作者：
Bosch N;Morell M;Ponsa I;Mercader JM;Armengol L;Estivill X
通讯作者：
Estivill X
影响因子：
2.6
作者：
Tantisira KG;Lazarus R;Litonjua AA;Klanderman B;Weiss ST
通讯作者：
Weiss ST
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
3.9
作者：
Deng, Libin;Zhang, Yuezheng;Zeng, Changqing
通讯作者：
Zeng, Changqing