1. Fetal hemoglobin in sickle cell anemia: genome-wide association studies suggest a regulatory region in the 5' olfactory receptor gene cluster.
- Author
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Solovieff N, Milton JN, Hartley SW, Sherva R, Sebastiani P, Dworkis DA, Klings ES, Farrer LA, Garrett ME, Ashley-Koch A, Telen MJ, Fucharoen S, Ha SY, Li CK, Chui DH, Baldwin CT, and Steinberg MH
- Subjects
- Adolescent, Adult, Black or African American genetics, Carrier Proteins genetics, Child, Child, Preschool, Chromosomes, Human, Pair 11 genetics, Chromosomes, Human, X genetics, Female, Genome-Wide Association Study, Hemoglobin E genetics, Hong Kong, Humans, Male, Nuclear Proteins genetics, Regulatory Sequences, Nucleic Acid, Repressor Proteins, Thailand, Young Adult, beta-Thalassemia genetics, Anemia, Sickle Cell blood, Anemia, Sickle Cell genetics, Fetal Hemoglobin genetics, Fetal Hemoglobin metabolism, Multigene Family, Polymorphism, Single Nucleotide, Receptors, Odorant genetics
- Abstract
In a genome-wide association study of 848 blacks with sickle cell anemia, we identified single nucleotide polymorphisms (SNPs) associated with fetal hemoglobin concentration. The most significant SNPs in a discovery sample were tested in a replication set of 305 blacks with sickle cell anemia and in subjects with hemoglobin E or beta thalassemia trait from Thailand and Hong Kong. A novel region on chromosome 11 containing olfactory receptor genes OR51B5 and OR51B6 was identified by 6 SNPs (lowest P = 4.7E-08) and validated in the replication set. An additional olfactory receptor gene, OR51B2, was identified by a novel SNP set enrichment analysis. Genome-wide association studies also validated a previously identified SNP (rs766432) in BCL11A, a gene known to affect fetal hemoglobin levels (P = 2.6E-21) and in Thailand and Hong Kong subjects. Elements within the olfactory receptor gene cluster might play a regulatory role in gamma-globin gene expression.
- Published
- 2010
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