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Global Genetic Architecture of an Erythroid Quantitative Trait Locus, HMIP‐2
Author(s) -
Menzel Stephan,
Rooks Helen,
Zelenika Diana,
Mtatiro Sia.,
Gnanakulasekaran Akshala,
Drasar Emma,
Cox Sharon,
Liu Li,
Masood Mariam,
Silver Nicholas,
Garner Chad,
Vasavda Nisha,
Howard Jo,
Makani Julie,
Adekile Adekunle,
Pace Betty,
Spector Tim,
Farrall Martin,
Lathrop Mark,
Thein Swee Lay
Publication year - 2014
Publication title -
annals of human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.537
H-Index - 77
eISSN - 1469-1809
pISSN - 0003-4800
DOI - 10.1111/ahg.12077
Subject(s) - biology , genetics , locus (genetics) , haplotype , allele , fetal hemoglobin , population , quantitative trait locus , expression quantitative trait loci , genetic architecture , evolutionary biology , gene , genotype , single nucleotide polymorphism , fetus , pregnancy , demography , sociology
Summary HMIP‐2 is a human quantitative trait locus affecting peripheral numbers, size and hemoglobin composition of red blood cells, with a marked effect on the persistence of the fetal form of hemoglobin, HbF, in adults. The locus consists of multiple common variants in an enhancer region for MYB (chr 6q23.3), which encodes the hematopoietic transcription factor cMYB. Studying a European population cohort and four African‐descended groups of patients with sickle cell anemia, we found that all share a set of two spatially separate HbF‐promoting alleles at HMIP‐2 , termed “A” and “B.” These typically occurred together (“A–B”) on European chromosomes, but existed on separate homologous chromosomes in Africans. Using haplotype signatures for “A” and “B,” we interrogated public population datasets. Haplotypes carrying only “A” or “B” were typical for populations in Sub‐Saharan Africa. The “A–B” combination was frequent in European, Asian, and Amerindian populations. Both alleles were infrequent in tropical regions, possibly undergoing negative selection by geographical factors, as has been reported for malaria with other hematological traits. We propose that the ascertainment of worldwide distribution patterns for common, HbF‐promoting alleles can aid their further genetic characterization, including the investigation of gene–environment interaction during human migration and adaptation.