Harvey C B, Hollox E J, Poulter M, Wang Y, Rossi M, Auricchio S, Iqbal T H, Cooper B T, Barton R, Sarner M, Korpela R, Swallow D M
MRC Human Biochemical Genetics Unit, University College London, UK.
Ann Hum Genet. 1998 May;62(Pt 3):215-23. doi: 10.1046/j.1469-1809.1998.6230215.x.
A genetic polymorphism is responsible for determining that some humans express lactase at high levels throughout their lives and are thus lactose tolerant, while others lose lactase expression during childhood and are lactose intolerant. We have previously shown that this polymorphism is controlled by an element or elements which act in cis to the lactase gene. We have also reported that 7 polymorphisms in the lactase gene are highly associated and lead to only 3 common haplotypes (A, B and C) in individuals of European extraction. Here we report the frequencies of these polymorphisms in Caucasians from north and south Europe and also from the Indian sub-continent, and show that the alleles differ in frequency, the B and C haplotypes being much more common in southern Europe and India. Allelic association studies with lactase persistence and non-persistence phenotypes show suggestive evidence of association of lactase persistence with certain alleles. This association was rather more clear in the analysis of small families, where haplotypes could be determined. Furthermore haplotype and RNA transcript analysis of 11 unrelated lactase persistent individuals shows that the persistence (highly expressed) allele is almost always on the A haplotype background. Non-persistence is found on a variety of haplotypes including A. Thus it appears that lactase persistence arose more recently than the DNA marker polymorphisms used here to define the main Caucasian haplotypes, possibly as a single mutation on the A haplotype background. The high frequency of the A haplotype in northern Europeans is consistent with the high frequency of lactase persistence.
一种基因多态性决定了一些人在其一生中都高水平表达乳糖酶，因此能够耐受乳糖，而另一些人在儿童期就失去乳糖酶表达，从而不耐受乳糖。我们之前已经表明，这种多态性受一个或多个与乳糖酶基因顺式作用的元件控制。我们还报道，乳糖酶基因中的7种多态性高度相关，在欧洲裔个体中仅导致3种常见单倍型（A、B和C）。在这里，我们报告了来自北欧和南欧以及印度次大陆的高加索人中这些多态性的频率，并表明等位基因频率存在差异，B和C单倍型在南欧和印度更为常见。对乳糖酶持续存在和非持续存在表型的等位基因关联研究显示，乳糖酶持续存在与某些等位基因存在关联的提示性证据。在小家系分析中这种关联更为明显，因为在小家系中可以确定单倍型。此外，对11名无关的乳糖酶持续存在个体的单倍型和RNA转录本分析表明，持续存在（高表达）等位基因几乎总是位于A单倍型背景上。非持续存在则出现在包括A在内的多种单倍型上。因此，乳糖酶持续存在似乎比这里用于定义主要高加索人单倍型的DNA标记多态性出现得更晚，可能是A单倍型背景上的一次单一突变。北欧人中A单倍型的高频率与乳糖酶持续存在的高频率一致。
