Enattah Nabil Sabri, Trudeau Aimee, Pimenoff Ville, Maiuri Luigi, Auricchio Salvatore, Greco Luigi, Rossi Mauro, Lentze Michael, Seo J K, Rahgozar Soheila, Khalil Insaf, Alifrangis Michael, Natah Sirajedin, Groop Leif, Shaat Nael, Kozlov Andrew, Verschubskaya Galina, Comas David, Bulayeva Kazima, Mehdi S Qasim, Terwilliger Joseph D, Sahi Timo, Savilahti Erkki, Perola Markus, Sajantila Antti, Järvelä Irma, Peltonen Leena
Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland.
Am J Hum Genet. 2007 Sep;81(3):615-25. doi: 10.1086/520705. Epub 2007 Aug 7.
A single-nucleotide variant, C/T(-13910), located 14 kb upstream of the lactase gene (LCT), has been shown to be completely correlated with lactase persistence (LP) in northern Europeans. Here, we analyzed the background of the alleles carrying the critical variant in 1,611 DNA samples from 37 populations. Our data show that the T(-13910) variant is found on two different, highly divergent haplotype backgrounds in the global populations. The first is the most common LP haplotype (LP H98) present in all populations analyzed, whereas the others (LP H8-H12), which originate from the same ancestral allelic haplotype, are found in geographically restricted populations living west of the Urals and north of the Caucasus. The global distribution pattern of LP T(-13910) H98 supports the Caucasian origin of this allele. Age estimates based on different mathematical models show that the common LP T(-13910) H98 allele (approximately 5,000-12,000 years old) is relatively older than the other geographically restricted LP alleles (approximately 1,400-3,000 years old). Our data about global allelic haplotypes of the lactose-tolerance variant imply that the T(-13910) allele has been independently introduced more than once and that there is a still-ongoing process of convergent evolution of the LP alleles in humans.
位于乳糖酶基因(LCT)上游14kb处的单核苷酸变体C/T(-13910),已被证明与北欧人的乳糖酶持续性(LP)完全相关。在此,我们分析了来自37个群体的1611份DNA样本中携带关键变体的等位基因背景。我们的数据表明,T(-13910)变体在全球人群中存在于两种不同的、高度分化的单倍型背景上。第一种是在所有分析群体中都存在的最常见的LP单倍型(LP H98),而其他单倍型(LP H8 - H12)则源自相同的祖先等位基因单倍型,见于生活在乌拉尔山脉以西和高加索以北的地理上受限的群体中。LP T(-13910) H98的全球分布模式支持了该等位基因起源于高加索地区的观点。基于不同数学模型的年龄估计表明,常见的LP T(-13910) H98等位基因(约5000 - 12000年)比其他地理上受限的LP等位基因(约1400 - 3000年)相对更古老。我们关于乳糖耐受变体全球等位基因单倍型的数据表明,T(-13910)等位基因已被多次独立引入,并且人类中LP等位基因的趋同进化过程仍在进行。