Centre for Genetic Improvement of Livestock, Animal and Poultry Science, Department, University of Guelph, Guelph, Ontario, Canada.
BMC Genomics. 2010 Jul 8;11:421. doi: 10.1186/1471-2164-11-421.
Effectiveness of genomic selection and fine mapping is determined by the level of linkage disequilibrium (LD) across the genome. Knowledge of the range of genome-wide LD, defined as a non-random association of alleles at different loci, can provide an insight into the optimal density and location of single-nucleotide polymorphisms (SNPs) for genome-wide association studies and can be a keystone for interpretation of results from QTL mapping.
Linkage disequilibrium was measured by /D'/ and r2 between 38,590 SNPs (spaced across 29 bovine autosomes and the X chromosome) using genotypes of 887 Holstein bulls. The average level of /D'/ and r2 for markers 40-60 kb apart was 0.72 and 0.20, respectively in Holstein cattle. However, a high degree of heterogeneity of LD was observed across the genome. The sample size and minor allele frequency had an effect on /D'/ estimates, however, r2 was not noticeably affected by these two factors. Syntenic LD was shown to be useful for verifying the physical location of SNPs. No differences in the extent of LD and decline of LD with distance were found between the intragenic and intergenic regions.
A minimal sample size of 444 and 55 animals is required for an accurate estimation of LD by /D'/ and r2, respectively. The use of only maternally inherited haplotypes is recommended for analyses of LD in populations consisting of large paternal half-sib families. Large heterogeneity in the pattern and the extent of LD in Holstein cattle was observed on both autosomes and the X chromosome. The extent of LD was higher on the X chromosome compared to the autosomes.
基因组选择和精细定位的有效性取决于基因组中连锁不平衡（LD）的水平。对全基因组范围内 LD 范围的了解，即不同基因座等位基因之间的非随机关联，可以深入了解全基因组关联研究中单核苷酸多态性（SNP）的最佳密度和位置，并为解释 QTL 定位结果提供关键依据。
利用 887 头荷斯坦公牛的基因型，通过 /D'/ 和 r2 测量了 38590 个 SNP（分布在 29 条牛染色体和 X 染色体上）之间的连锁不平衡。在荷斯坦牛中，间隔 40-60kb 的标记的平均 /D'/和 r2 水平分别为 0.72 和 0.20。然而，在整个基因组中观察到 LD 具有高度的异质性。样本量和次要等位基因频率对 /D'/估计值有影响，但这两个因素对 r2 没有明显影响。同线性 LD 被证明对于验证 SNP 的物理位置很有用。在基因内和基因间区域，LD 的程度和 LD 随距离的衰减没有发现差异。
分别通过 /D'/和 r2 准确估计 LD 需要至少 444 和 55 个个体的样本量。对于由大型父系半同胞家系组成的群体，建议仅使用母系遗传单体型进行 LD 分析。在荷斯坦牛中，无论是在常染色体还是 X 染色体上，都观察到 LD 模式和程度存在很大的异质性。与常染色体相比，X 染色体上的 LD 程度更高。
