Identifying Regions under Selection in SNP and Sequence data: Why are the Maasai Protected Against Hyperlipidemia and Heart Disease?

Gyan Bhanot

 Rutgers

ABSTRACT:  Field studies in the 70s suggested that the Maasai have a genetic switch which maintains cholesterol homeostasis. Analysis of HapMap 3 data, using allele frequency (AFS, Fst) and haplotype diversity (iHS) metrics, identified genomic regions and SNPs under strong, recent selection in the Maasai (MKK) samples. The most significant non-synonymous SNP under selection in MKK is at rs2241883, a TàC polymorphism in the FABP1 gene, known to reduce LDL and tri-glyceride levels in Europeans. A ~1Mb region on Chr2q21 is also under strong selection in MKK. This region contains the genes LCT and MCM6 in the lactase pathway as well as genes RAB3GAP1 and R3HDM1, associated with total cholesterol levels in the Framingham Heart Study.  Sanger sequencing of DNA from six MKK samples showed that the GàC polymorphism at rs4988233 in the MCM6 gene, associated with lactase persistence in Africans, is segregating in the Maasai at a frequency ~ 50%. Our results show that the Maasai are under strong selection in specific genomic regions, most likely for SNPs responsible for lactase persistence and cholesterol homeostasis. It also suggests that one might infer the diet of ancestral populations from SNPs in DNA extracted from gravesites.