title: The Xmn I site (-158, C----T) 5' to the G gamma gene: correlation with the Senegalese haplotype and G gamma globin expression.
abstract: There are three major African haplotypes associated with the sickle mutation: Benin (#19), Senegalese (#3), and Central African Republic (#20). Previous studies have suggested that the Xmn I site (-158 bp 5' to the G gamma gene) is associated with elevated levels of G gamma and with the Senegalese haplotype, while other investigators questioned this association. In order to clarify the issue, we have determined beta haplotypes, tested for the presence of the Xmn I site, and measured Hb F and G gamma expression levels in 143 American Black patients with sickle cell anemia. Haplotypes were determined using eight polymorphic sites in the beta-like globin gene cluster: Hinc II 5' to epsilon, Hind III in IVS-II G gamma and A gamma, Hinc II within and 3' to psi beta, Ava II in IVS-II of beta, and Hpa I and Bam HI 3' to beta. The G gamma /A gamma ratio was analyzed by high performance liquid chromatography using a C18 column. The Xmn I site was present in all 31 chromosomes with the Sengalese haplotype. Of the remaining 255 chromosomes with other haplotypes, only 2 (0.8%) had the Xmn I site present. There was significant correlation between the presence of the Xmn I site and increased G gamma /A gamma ratio in a dose-dependent manner. The Hb F level was not significantly increased in the presence of the Xmn I site. The data indicate that the Xmn I site maintains a G gamma /A gamma ratio typical of fetal life but does not necessarily cause elevation of Hb F. The latter seems to depend on factors other than the Xmn I site.
authors.affiliation: Cardeza Foundation for Hematologic Research, Department of Medicine, Thomas Jefferson University, Philadelphia, PA 19107.
authors.forename: S K
authors.initials: SK
authors.lastname: Ballas
authors.forename: C A
authors.initials: CA
authors.lastname: Talacki
authors.forename: K
authors.initials: K
authors.lastname: Adachi
authors.forename: E
authors.initials: E
authors.lastname: Schwartz
authors.forename: S
authors.initials: S
authors.lastname: Surrey
authors.forename: E
authors.initials: E
authors.lastname: Rappaport
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000755:Anemia, Sickle Cell / Q000097:blood / Q000235:genetics*; D001541:Benin / Q000208:ethnology; D002648:Child; D002675:Child, Preschool; D015252:Deoxyribonucleases, Type II Site-Specific; D005260:Female; D005319:Fetal Hemoglobin / Q000096:biosynthesis; D005786:Gene Expression Regulation; D005914:Globins / Q000096:biosynthesis* / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D010414:Pennsylvania; D012150:Polymorphism, Restriction Fragment Length; D012045:Regulatory Sequences, Nucleic Acid; D012675:Senegal / Q000208:ethnology
chemical_list: D005914:Globins; D005319:Fetal Hemoglobin; C028649:endodeoxyribonuclease XmnI; D015252:Deoxyribonucleases, Type II Site-Specific