Research Department of Genetics, Evolution and Environment, University College London, London WC1E 6BT, UK.
BMC Evol Biol. 2010 Feb 9;10:36. doi: 10.1186/1471-2148-10-36.
The ability of adult humans to digest the milk sugar lactose - lactase persistence - is a dominant Mendelian trait that has been a subject of extensive genetic, medical and evolutionary research. Lactase persistence is common in people of European ancestry as well as some African, Middle Eastern and Southern Asian groups, but is rare or absent elsewhere in the world. The recent identification of independent nucleotide changes that are strongly associated with lactase persistence in different populations worldwide has led to the possibility of genetic tests for the trait. However, it is highly unlikely that all lactase persistence-associated variants are known. Using an extensive database of lactase persistence phenotype frequencies, together with information on how those data were collected and data on the frequencies of lactase persistence variants, we present a global summary of the extent to which current genetic knowledge can explain lactase persistence phenotype frequency.
We used surface interpolation of Old World lactase persistence genotype and phenotype frequency estimates obtained from all available literature and perform a comparison between predicted and observed trait frequencies in continuous space. By accommodating additional data on sample numbers and known false negative and false positive rates for the various lactase persistence phenotype tests (blood glucose and breath hydrogen), we also apply a Monte Carlo method to estimate the probability that known lactase persistence-associated allele frequencies can explain observed trait frequencies in different regions.
Lactase persistence genotype data is currently insufficient to explain lactase persistence phenotype frequency in much of western and southern Africa, southeastern Europe, the Middle East and parts of central and southern Asia. We suggest that further studies of genetic variation in these regions should reveal additional nucleotide variants that are associated with lactase persistence.
成年人消化乳糖（乳糖酶持续性）的能力是一种显性孟德尔特征，一直是遗传、医学和进化研究的主题。乳糖酶持续性在欧洲血统的人群中很常见，也存在于一些非洲、中东和南亚群体中，但在世界其他地方则很少见或不存在。最近发现的与世界各地乳糖酶持续性相关的独立核苷酸变化，使得对该特征进行基因检测成为可能。然而，极不可能所有与乳糖酶持续性相关的变异都已被发现。利用一个广泛的乳糖酶持续性表型频率数据库，以及关于这些数据是如何收集的信息和乳糖酶持续性变异频率的数据，我们对当前遗传知识在多大程度上可以解释乳糖酶持续性表型频率进行了全球总结。
我们使用旧世界乳糖酶持续性基因型和表型频率估计值的表面插值，从所有可用文献中获得，并在连续空间中对预测和观察到的特征频率进行比较。通过容纳有关各种乳糖酶持续性表型测试（血糖和呼气氢）的样本数量和已知假阴性和假阳性率的额外数据，我们还应用蒙特卡罗方法来估计已知的乳糖酶持续性相关等位基因频率可以解释不同地区观察到的特征频率的概率。
目前，乳糖酶持续性基因型数据不足以解释非洲西部和南部、东南欧、中东和亚洲中部和南部部分地区的乳糖酶持续性表型频率。我们建议，对这些地区遗传变异的进一步研究应该揭示与乳糖酶持续性相关的其他核苷酸变异。
