title: Haplotypes in SS patients from Nigeria; characterization of one atypical beta S haplotype no. 19 (Benin) associated with elevated HB F and high G gamma levels.
abstract: We have determined the haplotypes of 669 beta S and 109 beta A chromosomes from numerous members of 297 Nigerian families of various ethnic backgrounds. Among the beta S chromosomes, haplotype 19 was detected in 93.2%, haplotype 17 in 3.4%, and haplotype 20 in 0.1%, while 2.4% represented atypical haplotypes. As many as 60.6% of the beta A chromosomes exhibited haplotype 19 mutations, 8.2% had haplotype 3, and 1.8% had haplotype 20. Two siblings with elevated Hb F and G gamma levels were heterozygous for a beta S chromosome with haplotype 19 and a second chromosome with a hybrid haplotype (termed 19 B). In this hybrid chromosome, haplotype 3-like locus control region (LCR) [hypersensitive site-2 (HS-2)] sequences are in juxtaposition to those of the 5' flanking region of the G gamma promoter of a beta S chromosome with haplotype 19. The presence of this hybrid chromosome is associated with high G gamma values in individuals with both sickle cell anemia (SS) and sickle cell trait (AS); it closely resembles another hybrid beta S chromosome, termed 19 A, observed in a previously reported Turkish SS patient who was homozygous for this chromosome and had high Hb F and high G gamma values. In both instances, it is hypothesized that the haplotype 3-like sequences of the LCR HS-2 contain genetic determinants that can combine with factors produced during hematopoietic stress, resulting in increased gamma-globin gene expression.
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta 30912-2100.
authors.forename: A D
authors.initials: AD
authors.lastname: Adekile
authors.forename: M N
authors.initials: MN
authors.lastname: Kitundu
authors.forename: L H
authors.initials: LH
authors.lastname: Gu
authors.forename: K D
authors.initials: KD
authors.lastname: Lanclos
authors.forename: O O
authors.initials: OO
authors.lastname: Adeodu
authors.forename: T H
authors.initials: TH
authors.lastname: Huisman
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000755:Anemia, Sickle Cell / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005319:Fetal Hemoglobin / Q000032:analysis*; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D009549:Nigeria; D011401:Promoter Regions, Genetic; D044469:Racial Groups; D012737:Sex Factors
chemical_list: D005319:Fetal Hemoglobin