Fine-mapping at three loci known to affect fetal hemoglobin levels explains additional genetic variation.

Pubmed ID: 21057501

Pubmed Central ID: PMC3740938

Journal: Nature genetics

Publication Date: Dec. 1, 2010

Affiliation: Montreal Heart Institute, Montréal, Québec, Canada.

MeSH Terms: Humans, Base Sequence, Polymorphism, Single Nucleotide, Anemia, Sickle Cell, Fetal Hemoglobin, Genome, Human, Genetic Loci, Mutation, Missense, Physical Chromosome Mapping, Black or African American

Grants: N01-HV-48194, N01HV48194

Authors: Lettre G, Sankaran VG, Hirschhorn JN, Orkin SH, Galarneau G, Palmer CD

Cite As: Galarneau G, Palmer CD, Sankaran VG, Orkin SH, Hirschhorn JN, Lettre G. Fine-mapping at three loci known to affect fetal hemoglobin levels explains additional genetic variation. Nat Genet 2010 Dec;42(12):1049-51. Epub 2010 Nov 7.

Studies:

Abstract

We used resequencing and genotyping in African Americans with sickle cell anemia (SCA) to characterize associations with fetal hemoglobin (HbF) levels at the BCL11A, HBS1L-MYB and β-globin loci. Fine-mapping of HbF association signals at these loci confirmed seven SNPs with independent effects and increased the explained heritable variation in HbF levels from 38.6% to 49.5%. We also identified rare missense variants that causally implicate MYB in HbF production.