Fine-mapping at three loci known to affect fetal hemoglobin levels explains additional genetic variation
2010; Nature Portfolio; Volume: 42; Issue: 12 Linguagem: Inglês
10.1038/ng.707
ISSN1546-1718
AutoresGeneviève Galarneau, Nicholette D. Palmer, Vijay G. Sankaran, Stuart H. Orkin, Joel N. Hirschhorn, Guillaume Lettre,
Tópico(s)Blood groups and transfusion
ResumoGuillaume Lettre and colleagues report fine-mapping at three loci associated with variation in fetal hemoglobin levels. Their findings implicate multiple common and rare variants at these loci that collectively explain a substantial fraction of the heritable variation in this trait. 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.
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