Lactase persistence and lipid pathway selection in the Maasai

Area of Science:

• Human Genetics
• Population Genomics
• Nutritional Genomics

Background:

• The Maasai people traditionally consume a diet rich in lactose, fat, and cholesterol.
• Despite their diet, Maasai exhibit low blood cholesterol and low incidence of cardiovascular diseases.
• Previous studies suggested genetic adaptations for cholesterol homeostasis in the Maasai population.

Purpose of the Study:

• To identify genomic regions and single nucleotide polymorphisms (SNPs) under recent selection in the Maasai population.
• To investigate genetic adaptations related to lactase persistence and cholesterol regulation.

Main Methods:

• Analysis of HapMap 3 data using Fixation Index (Fst), integrated Haplotype Score (iHS), and Cross Population Extended Haplotype Homozygosity (XP-EHH).
• Identification of candidate SNPs and genomic regions associated with lactase persistence and cholesterol metabolism.
• Sanger sequencing of DNA from Maasai samples to confirm specific polymorphisms.

Main Results:

• A 1.7 Mb region on Chr2q21, containing LCT, MCM6, and Rab3GAP1 genes, showed strong signals of selection.
• The rs2241883 SNP in FABP1 was identified as a strong candidate for selection, potentially reducing LDL and triglyceride levels.
• A lactase persistence polymorphism (GC-14010) in MCM6 was found at high frequency (~58%) in the Maasai.
• The CYP3A gene cluster, involved in cholesterol metabolism, was also identified as a candidate locus under selection.

Conclusions:

• The Maasai population exhibits genetic adaptations for lactase persistence and cholesterol regulation.
• Specific genomic regions and genes, including LCT, MCM6, Rab3GAP1, FABP1, and CYP3A, are under selection.
• These adaptations likely contribute to the Maasai's ability to maintain low cholesterol levels and resist cardiovascular diseases despite their traditional diet.