Department of Human Genetics, University of Chicago, Illinois, USA.
Genet Epidemiol. 2011 Sep;35(6):557-67. doi: 10.1002/gepi.20606. Epub 2011 Jul 18.
We present a novel method, IBDLD, for estimating the probability of identity by descent (IBD) for a pair of related individuals at a locus, given dense genotype data and a pedigree of arbitrary size and complexity. IBDLD overcomes the challenges of exact multipoint estimation of IBD in pedigrees of potentially large size and eliminates the difficulty of accommodating the background linkage disequilibrium (LD) that is present in high-density genotype data. We show that IBDLD is much more accurate at estimating the true IBD sharing than methods that remove LD by pruning SNPs and is highly robust to pedigree errors or other forms of misspecified relationships. The method is fast and can be used to estimate the probability for each possible IBD sharing state at every SNP from a high-density genotyping array for hundreds of thousands of pairs of individuals. We use it to estimate point-wise and genomewide IBD sharing between 185,745 pairs of subjects all of whom are related through a single, large and complex 13-generation pedigree and genotyped with the Affymetrix 500 k chip. We find that we are able to identify the true pedigree relationship for individuals who were misidentified in the collected data and estimate empirical kinship coefficients that can be used in follow-up QTL mapping studies. IBDLD is implemented as an open source software package and is freely available.
我们提出了一种新的方法，即 IBDLD，用于估计一对相关个体在给定密集基因型数据和任意大小和复杂程度的家系中特定位置的同源（IBD）的概率。IBDLD 克服了在潜在大型家系中精确多点估计 IBD 的挑战，并消除了适应高密度基因型数据中存在的背景连锁不平衡（LD）的困难。我们表明，IBDLD 在估计真实 IBD 共享方面比通过修剪 SNP 去除 LD 的方法准确得多，并且对家谱错误或其他形式的指定关系错误具有高度的稳健性。该方法速度很快，可用于从高密度基因分型阵列中估计数十万对个体的每个 SNP 的每个可能 IBD 共享状态的概率。我们使用它来估计 185745 对个体之间的点和全基因组 IBD 共享，这些个体全部通过一个单一的、大型且复杂的 13 代家谱相关，并使用 Affymetrix 500k 芯片进行基因分型。我们发现，我们能够识别在收集的数据中被错误识别的个体的真实家谱关系，并估计可用于后续 QTL 映射研究的经验亲缘系数。IBDLD 作为开源软件包实现，可免费使用。
