Stability or Variation? Patterns of Lactase Gene and Its Enhancer Region Distributions in Brazilian Amerindians Deise C. Friedrich, 1 Sidia M. Callegari-Jacques, 1,2 M. Luiza Petzl-Erler, 3 Luiza Tsuneto, 3 Francisco M. Salzano, 1 and Mara H. Hutz 1 * 1 Departamento de Gene ´tica, Universidade Federal do Rio Grande do Sul, Caixa Postal 15053, 91501-970, Porto Alegre, RS, Brazil 2 Departamento de Estatı´stica, Universidade Federal do Rio Grande do Sul, Campus do Vale, 91509-900 Porto Alegre, RS, Brazil 3 Departamento de Gene ´tica, Universidade Federal do Parana ´ , Caixa Postal 19071, 81531-990 Curitiba, PR, Brazil KEY WORDS Amerindian populations; selection; genetic structure; LCT gene ABSTRACT Lactase persistence (LP) is the pheno- typic trait in which lactase secretion is maintained during adulthood. LP is due to mutations in the LCT enhancer region, located 14-kb upstream of the gene. In Europeans, the 213910*T allele is associated with LP. In Africans this allele is rare while other mutations in this same region were related to LP. The LCT is highly polymorphic in human populations, but so far Brazilian Amerindians had not been investigated for these polymorphisms or for the presence of LP mutations. We describe the genetic di- versity of the LCT region and the presence of LP enhancer mutations in four native Brazilian populations (Guarani-Kaiowa ´, Guarani–N ˜ andeva, Kaingang, and Xavante). Twelve polymorphisms were genotyped by PCR- based methods. The 213910*T allele varied from 0.5% in the Xavante to 7.6% in the Guarani–N ˜ andeva. These fre- quencies probably derive from European sources and they correlate with non-native admixture proportions previ- ously estimated for these groups. But since admixture is virtually absent in the Xavante, we suggest that the pres- ence of the LP allele could have been determined by a de novo mutation. No other mutations in the 214 kb enhancer region were found. The LCT was highly poly- morphic in the present sample showing 15 haplotypes with a heterogeneous distribution among the four Amerin- dian populations. This diversity could be due to drift, as indicated by the neutrality test performed. Am J Phys Anthropol 147:427–432, 2012. V V C 2012 Wiley Periodicals, Inc. Brazil was colonized by people of Asian origin, who arrived in the American continent through the Bering Strait about 15–18 thousand years ago (Salzano, 2011). These peoples spread all over North, Central, and South America and they are now known as Amerindians. At the time of the Conquest, the Spanish and Portuguese explorers found an aboriginal population estimated between 7 and 39 million individuals. Some societies depended heavily on agriculture, others practiced a mix of farming, fishing, hunting, and gathering whereas others were hunters and gatherers only (Salzano and Callegari-Jacques, 1988). Cattle were not present at that time; however it was introduced in the Americas by Columbus in his second trip in 1493, and in Brazil the first herds were brought by the Portuguese in 1534 (Primo, 1992). Polymorphisms across the 70-kb lactase gene (LCT) have been previously described (Boll et al., 1991; Harvey et al., 1995). The worldwide distribution of their derived haplotypes showed that four haplotypes (A, B, C, and U) were observed at frequencies higher than 0.05. Haplo- type A is the most common in all populations except in Sub-Saharan Africans; it has its highest frequency in northern Europeans. The B haplotype is present in all populations except Bantu-speaking South Africans. Haplotype C is also present in all populations but it is more common in southern Europe and India whereas, the U haplotype is rare in Indo-European populations (Harvey et al., 1998; Hollox et al., 2001). Most human adults downregulate the production of intestinal lactase after weaning. Lactase is necessary for the digestion of lactose, the main carbohydrate in milk, and without it, milk consumption can lead to bloating, flatulence, cramps, and nausea (Swallow, 2003). Persist- ence of small-intestinal lactase production into adult life in humans is caused by genetic differences cis-acting near the lactase gene (Wang et al., 1995), which enables some alleles to escape the developmental downregulation characteristic of the ancestral state. The first allele to be identified, –13910*T (rs4988235) was discovered in a north-European sample and is in high linkage disequili- brium with 222018*A allele (Enattah et al., 2002). The 213910*T is present on the background of a single very extended Haplotype A (Hollox et al., 2001; Poulter et al., 2003; Bersaglieri et al., 2004; Coelho et al., 2005). The Additional Supporting Information may be found in the online version of this article. Grant sponsor: Conselho Nacional de Desenvolvimento Cientı ´fico e Tecnolo ´gico, Brazil. *Correspondence to: Mara H. Hutz, Departamento de Gene ´tica, UFRGS, Caixa Postal 15053, 91501-970 Porto Alegre, RS, Brazil. E-mail: mara.hutz@ufrgs.br Received 10 August 2011; accepted 7 December 2011 DOI 10.1002/ajpa.22010 Published online 23 January 2012 in Wiley Online Library (wileyonlinelibrary.com). V V C 2012 WILEY PERIODICALS, INC. AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY 147:427–432 (2012)