Fine-mapping at three loci known to affect fetal hemoglobin levels explains additional genetic variation.
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.
Montreal Heart Institute, Montréal, Québec, Canada.
Geneviève
G
Galarneau
Cameron D
CD
Palmer
Vijay G
VG
Sankaran
Stuart H
SH
Orkin
Joel N
JN
Hirschhorn
Guillaume
G
Lettre
D001741:Black or African American / Q000235:genetics; D000755:Anemia, Sickle Cell / Q000235:genetics; D001483:Base Sequence; D005319:Fetal Hemoglobin / Q000235:genetics*; D056426:Genetic Loci / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D020125:Mutation, Missense / Q000235:genetics; D020161:Physical Chromosome Mapping / Q000379:methods*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
D005319:Fetal Hemoglobin