The Genetic Variation of Lactase Persistence Alleles in Sudan and South Sudan.

Nina Hollfelder,Carina M Schlebusch,Hiba Babiker,Mattias Jakobsson,Lena Granehäll

doi:10.1093/gbe/evab065

Abstract

Lactase persistence (LP) is a well-studied example of a Mendelian trait under selection in some human groups due to gene-culture coevolution. We investigated the frequencies of genetic variants linked to LP in Sudanese and South Sudanese populations. These populations have diverse subsistence patterns, and some are dependent on milk to various extents, not only from cows but also from other livestock such as camels and goats. We sequenced a 316-bp region involved in regulating the expression of the LCT gene on chromosome 2, which encompasses five polymorphisms that have been associated with LP. Pastoralist populations showed a higher frequency of LP-associated alleles compared with nonpastoralist groups, hinting at positive selection also among northeast African pastoralists. Among the LP variants, the -14009:G variant occurs at the highest frequency among the investigated populations, followed by the -13915:G variant, which is likely of Middle Eastern origin, consistent with Middle Eastern gene flow to the Sudanese populations. There was no incidence of the “East African” LP allele (-14010:C) in the Sudanese and South Sudanese groups, and only one heterozygous individual for the “European” LP allele (-13910:T), suggesting limited recent admixture from these geographic regions. The Beja population of the Beni Amer show three different LP variants at substantial and similar levels, resulting in one of the greatest aggregation of LP variants among all populations across the world.

Highlights

Lactase persistence (LP) is the ability to digest the milk sugar, lactose, at an adult age
None of the LP-associated single nucleotide polymorphisms (SNPs) are significantly deviating from Hardy–Weinberg equilibrium in the investigated Sudanese and South Sudanese (SASS) populations
The LP-associated alleles -13907:G, -13915:G, and -14009:G appear in frequencies up to 0.34 in Sudan, mainly in Sudanese Arab, Nubian, and Beja populations

Summary

Introduction

Lactase persistence (LP) is the ability to digest the milk sugar, lactose, at an adult age. Other SNPs have been identified to be the putative causal variants in these regions: -13907:C>G (rs41525747) in Ethiopia and Saudi Arabia, -13915:T>G (rs41380347) in Saudi Arabia, -14009:T>G (rs869051967) in African Arab groups, and -14010:G>C (rs145946881) in Kenya and Tanzania (Ingram et al 2007, 2009; Tishkoff et al 2007; Jones et al 2013; Priehodova et al 2014; Ranciaro et al 2014; Liebert et al 2016) These polymorphisms have been shown to increase LCT promoter expression in vitro (Ingram et al 2007; Tishkoff et al 2007; Enattah et al 2008; Jensen et al 2011; Olds et al 2011; Jones et al 2013; Liebert et al 2016), and the -13910:C>T variant was recently identified as the putative causal variant for LP in a genome-wide association study (GWAS) study in the Fulani population of the African Sahel/Savannah belt (Vicente et al 2019). There is evidence for a selective sweep on 14010:G>C (Tishkoff et al 2007) that shows a stronger selection coefficient in the Massai in Kinyawa, Kenya (MKK) than the allele -13910:T shows in the European (CEU) population (Altshuler et al 2010; Schlebusch et al 2013), pointing to a strong increase in fitness for LP individuals in African pastoralist populations

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Conclusion