Lactase (LCT) gene is spatially limited along the anterior-posterior gut axis. The gene encodes for an enzyme known as lactase which is responsible for digesting lactose (the sugar of milk) into glucose and galactose. Lactose intolerance is the most common enzyme deficiency worldwide with the highest prevalence rates among the blacks from Native America, Asian America, and African roots. In contrast, races descended from northern Europe or from the northwestern Indian subcontinent have less chance to have lactose intolerance. This is thought to be an evolutionary advantage because people from northern Europe have a tradition to consume dairy products.
The lactase (LCT) gene has been mapped to the long arm of chromosome 2, but it is not yet known whether lactase persistence and non-persistence are linked to this locus. LCT gene sizes 49,335 bases and it contains 17 exons.
Imtiaz et al. (2007) sequenced DNA from 432 individuals from five different regions of Saudi Arabia to uncover variants within the 400 bp region around the lactase persistence variant C-13910T, which is located in intron 13 of the MCM6 gene. Only two individuals had the abovementioned variant, while 77% of the samples had another variant that is located in the vicinity of the first one; the T-13915G variant. Enzymatic assays on 25 intestinal biopsy samples showed highly significant correlation between lactase activity and the T-13915G genotypes. Imtiaz et al. (2007) concluded that The T-13915G variant is the founder mutation of lactase persistence in the urban Saudi population.
Enattah et al. (2008) studied the molecular basis for lactase persistence (LP) in Saudis, who are known to have high prevalence of this phenotype. The results indicated the absence of the European T-13910 variant that is located in the enhancer element of the lactase gene and is associated with LP. Moreover, two new variants involving the lactase gene were found in Saudis as a compound allele: T-13915G within the -13910 enhancer region and a synonymous SNP in the exon 17 of the MCM6 gene T-3712C -3712 bp from the lactase gene. These two variants were examined functionally in vitro and they appear to be required for the enhancer effect, probably through the binding of the hepatic nuclear factor 1 alpha (HNF1 alpha). A selection coefficient, as high as 0.04, was found for the LP phenotype for the compound allele. Analyzing ancestral haplotypes indicates that the compound Arab allele had arisen independently and this supports that idea that different histories of adaptation to milk culture happened in different geographical localities.
Tishkoff et al. (2006) examined genotype-phenotype associations in more than 40 Sudanese individuals and identified, at least one, previously undescribed variants associated with the lactase persistence trait, each of which arose independently from the European T-13910 allele. Materials and methods involved in the study were DNA samples, phenotype test, sequence analysis, single nuclear polymorphism (SNP) genotyping, genotype-phenotype association tests, combined population meta- analysis, ANOVA, homozygosity plots, haplotype phase estimation, and vector, transfection and expression assay. Sequencing the 3,314 bp of intron 13 was performed in order to identify SNPs associated with regulation of the lactase persistence trait. A newly discovered SNP (C/G-13907) was marginally significantly associated with lactase persistence in the Beja population from northern Sudan. The C-13907 and G-13915 alleles were at 21% and 12% frequency, respectively, in the Afro-Asiatic Beja populations. Data in the study of Tishkoff et al. (2006) provide a marked example of convergent evolution due to strong selective pressure resulting from shared cultural traits; including animal domestication and adult milk consumption.