Liebert Anke, López Saioa, Jones Bryony Leigh, Montalva Nicolas, Gerbault Pascale, Lau Winston, Thomas Mark G, Bradman Neil, Maniatis Nikolas, Swallow Dallas M
Research Department of Genetics, Evolution and Environment, University College London, Darwin Building, Gower Street, London, WC1E 6BT, UK.
Department of Paediatrics, University of Cambridge, Box 116, Level 8, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
Hum Genet. 2017 Nov;136(11-12):1445-1453. doi: 10.1007/s00439-017-1847-y. Epub 2017 Oct 23.
The genetic trait of lactase persistence (LP) is associated with at least five independent functional single nucleotide variants in a regulatory region about 14 kb upstream of the lactase gene [-13910T (rs4988235), -13907G (rs41525747), -13915G (rs41380347), -14009G (rs869051967) and -14010*C (rs145946881)]. These alleles have been inferred to have spread recently and present-day frequencies have been attributed to positive selection for the ability of adult humans to digest lactose without risk of symptoms of lactose intolerance. One of the inferential approaches used to estimate the level of past selection has been to determine the extent of haplotype homozygosity (EHH) of the sequence surrounding the SNP of interest. We report here new data on the frequencies of the known LP alleles in the 'Old World' and their haplotype lineages. We examine and confirm EHH of each of the LP alleles in relation to their distinct lineages, but also show marked EHH for one of the older haplotypes that does not carry any of the five LP alleles. The region of EHH of this (B) haplotype exactly coincides with a region of suppressed recombination that is detectable in families as well as in population data, and the results show how such suppression may have exaggerated haplotype-based measures of past selection.
乳糖酶持久性（LP）的遗传特征与乳糖酶基因上游约14 kb调控区域中的至少五个独立的功能性单核苷酸变异有关[-13910T（rs4988235）、-13907G（rs41525747）、-13915G（rs41380347）、-14009G（rs869051967）和-14010*C（rs145946881）]。据推断，这些等位基因是最近才传播开来的，而当今的频率归因于对成年人类消化乳糖而无乳糖不耐受症状风险能力的正选择。用于估计过去选择水平的一种推断方法是确定感兴趣的单核苷酸多态性（SNP）周围序列的单倍型纯合性程度（EHH）。我们在此报告“旧世界”中已知LP等位基因频率及其单倍型谱系的新数据。我们研究并确认了每个LP等位基因相对于其不同谱系的EHH，但也显示出一种较古老单倍型具有明显的EHH，该单倍型不携带五个LP等位基因中的任何一个。这种（B）单倍型的EHH区域与在家族以及群体数据中可检测到的重组抑制区域完全重合，结果表明这种抑制可能如何夸大了基于单倍型的过去选择的测量方法。
