Genetics of fetal hemoglobin in Tanzanian and British patients with sickle cell anemia.
Fetal hemoglobin (HbF, α(2)γ(2)) is a major contributor to the remarkable phenotypic heterogeneity of sickle cell anemia (SCA). Genetic variation at 3 principal loci (HBB cluster on chromosome 11p, HBS1L-MYB region on chromosome 6q, and BCL11A on chromosome 2p) have been shown to influence HbF levels and disease severity in β-thalassemia and SCA. Previous studies in SCA, however, have been restricted to populations from the African diaspora, which include multiple genealogies. We have investigated the influence of these 3 loci on HbF levels in sickle cell patients from Tanzania and in a small group of African British sickle patients. All 3 loci have a significant impact on the trait in both patient groups. The results suggest the presence of HBS1L-MYB variants affecting HbF in patients who are not tracked well by European-derived markers, such as rs9399137. Additional loci may be identified through independent genome-wide association studies in African populations.
Muhimbili University of Health and Allied Sciences, Dar-es-Salaam, Tanzania. jmakani@muhas.ac.tz
Julie
J
Makani
Stephan
S
Menzel
Siana
S
Nkya
Sharon E
SE
Cox
Emma
E
Drasar
Deogratius
D
Soka
Albert N
AN
Komba
Josephine
J
Mgaya
Helen
H
Rooks
Nisha
N
Vasavda
Gregory
G
Fegan
Charles R
CR
Newton
Martin
M
Farrall
Swee Lay
SL
Thein
D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000208:ethnology* / Q000235:genetics*; D044383:Black People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D005319:Fetal Hemoglobin / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013636:Tanzania; D006113:United Kingdom; D044465:White People / Q000235:genetics; D055815:Young Adult
D005319:Fetal Hemoglobin