Global genetic architecture of an erythroid quantitative trait locus, HMIP-2.

Autor: Menzel S; King's College London, London, UK., Rooks H; King's College London, London, UK., Zelenika D; Centre National de Génotypage, Evry, France., Mtatiro SN; King's College London, London, UK.; Muhimbili University, Dar es Salaam, Tanzania., Gnanakulasekaran A; King's College London, London, UK., Drasar E; King's College London, London, UK.; King's College Hospital NHS Foundation Trust, London, UK., Cox S; Muhimbili University, Dar es Salaam, Tanzania., Liu L; University of Texas at Dallas, Richardson, TX, USA., Masood M; King's College London, London, UK., Silver N; King's College London, London, UK., Garner C; University of California Irvine School of Medicine, Irvine, CA, USA., Vasavda N; King's College London, London, UK., Howard J; King's College London, London, UK.; Guy's and St Thomas' Hospital NHS Foundation Trust, London, UK., Makani J; Muhimbili University, Dar es Salaam, Tanzania., Adekile A; Faculty of Medicine, Kuwait University, Kuwait., Pace B; Georgia Regents University, Augusta, GA, USA., Spector T; King's College London, London, UK., Farrall M; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK., Lathrop M; McGill University, Montreal, Canada., Thein SL; King's College London, London, UK.; King's College Hospital NHS Foundation Trust, London, UK.
Jazyk: angličtina
Zdroj: Annals of human genetics [Ann Hum Genet] 2014 Nov; Vol. 78 (6), pp. 434-51. Date of Electronic Publication: 2014 Jul 29.
DOI: 10.1111/ahg.12077
Abstrakt: 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.
(© 2014 The Authors. Annals of Human Genetics published by University College London (UCL) and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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