Persistence or non-persistence of lactase expression into adult life is a polymorphic trait that has been attributed to a single nucleotide polymorphism (C-13910T) in an enhancer element 13.9 kb upstream of the lactase gene (LCT). The -13910*T allele occurs at very high frequency in northern Europeans as part of a very long haplotype (known as A), and promotes binding of the transcription factor Oct-1. However, -13910*T is at very low frequency in many African milk drinking pastoralist groups where lactase persistence phenotype has been reported at high frequency. We report here for the first time, a cohort study of lactose digester and non-digester Sudanese volunteers and show there is no association of -13910*T or the A haplotype with lactase persistence. We support this finding with new genotype/phenotype frequency comparisons in pastoralist groups of eastern African and Middle Eastern origin. Resequencing revealed three new SNPs in close proximity to -13910*T, two of which are within the Oct-1 binding site. The most frequent of these (-13915*G) is associated with lactose tolerance in the cohort study, providing evidence for a cis-acting effect. Despite its location, -13915*G abolishes, rather than enhances Oct-1 binding, indicating that this particular interaction is unlikely to be involved in lactase persistence. This study reveals the complexity of this phenotypic polymorphism and highlights the limitations of C-13910T as a diagnostic test for lactase persistence status, at least for people with non-European ancestry.

Persistence of intestinal lactase into adulthood allows humans to use milk from other mammals as a source of food and water. This genetic trait has arisen by convergent evolution and the derived alleles of at least three different single nucleotide polymorphisms (-13910C>T, -13915T>G, -14010G>C) are associated with lactase persistence in different populations. Each allele occurs on an extended haplotype, consistent with positive directional selection. The SNPs are located in an 'enhancer' sequence in an intron of a neighboring gene (MCM6) and modulate lactase transcription in vitro. However, a number of lactase persistent individuals carry none of these alleles, but other low-frequency single nucleotide polymorphisms have been observed in the same region. Here we examine a cohort of 107 milk-drinking Somali camel-herders from Ethiopia. Eight polymorphic sites are identified in the enhancer. -13915*G and -13907*G (a previously reported candidate) are each significantly associated with lactase persistence. A new allele, -14009*G, has borderline association with lactase persistence, but loses significance after correction for multiple testing. Sequence diversity of the enhancer is significantly higher in the lactase persistent members of this and a second cohort compared with non-persistent members of the two groups (P = 7.7 x 10(-9) and 1.0 x 10(-3)). By comparing other loci, we show that this difference is not due to population sub-structure, demonstrating that increased diversity can accompany selection. This contrasts with the well-documented observation that positive selection decreases diversity by driving up the frequency of a single advantageous allele, and has implications for association studies.

The persistent expression of lactase into adulthood in humans is a recent genetic adaptation that allows the consumption of milk from other mammals after weaning. In Europe, a single allele (-13910(∗)T, rs4988235) in an upstream region that acts as an enhancer to the expression of the lactase gene LCT is responsible for lactase persistence and appears to have been under strong directional selection in the last 5,000 years, evidenced by the widespread occurrence of this allele on an extended haplotype. In Africa and the Middle East, the situation is more complicated and at least three other alleles (-13907(∗)G, rs41525747; -13915(∗)G, rs41380347; -14010(∗)C, rs145946881) in the same LCT enhancer region can cause continued lactase expression. Here we examine the LCT enhancer sequence in a large lactose-tolerance-tested Ethiopian cohort of more than 350 individuals. We show that a further SNP, -14009T>G (ss 820486563), is significantly associated with lactose-digester status, and in vitro functional tests confirm that the -14009(∗)G allele also increases expression of an LCT promoter construct. The derived alleles in the LCT enhancer region are spread through several ethnic groups, and we report a greater genetic diversity in lactose digesters than in nondigesters. By examining flanking markers to control for the effects of mutation and demography, we further describe, from empirical evidence, the signature of a soft selective sweep.

Background: Color vision deficiency or colorblindness, is the inability or reduced ability to distinguish different color spectra, particularly, red & green under normal lighting conditions with unaided eye. Redgreen colorblindness is heritable genetic disorder and most prevalent type of color vision deficiency and its incidence varies between different ethnicity and sex and shows disparity in different parts/regions of the world. Objectives: This study was conducted to find out the prevalence of colorblindness in Eastern part of Ethiopia and identify its distribution among Harari, Oromo and Ethio-Somali ethnic groups. Methods: A total of 2103 (1043 male & 1060 female) students belonging to the three ethnic groups were randomly selected from nine selected primary schools and were screened for color vision deficiency by using Ishihara's tests for color vision deficiency and the data analysis was carried out with SPSS version 16.0. Results: Among those screened for color vision deficiency, 33 of them (1.6%) were diagnosed with colorblindness out of which 31 were male and 2 were female. Out of this; 15, 7 and 11 were from Harari, Oromo and Somali ethnicity respectively. The highest incidence was observed among Harari males (4.2%) and no color vision deficiency was recorded among Oromo females. Deuteronomally was the most frequent color vision defect detected (16, 48.5%) and protanopia was the least detected color vision deficiency with 4 cases (12.1%). Conclusion: Results from this study show similar prevalence rate with previously reported study in Ethiopia for Harari ethnic group but lower prevalence rates for Somali and Oromo ethnic groups. Early detection of colorblindness is important for children to select their future profession and take necessary precautions in their everyday activities. Families and other concerned bodies should also take the case of children with colorblindness into consideration while dealing with them.

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