title: Hemoglobinopathies among the Gond tribal groups of central India; interaction of alpha- and beta-thalassemia with beta chain variants.
abstract: We have investigated the frequencies and types of alpha-thal, beta-thal, and Hb variants among nearly 200 inhabitants of villages in the Mandla and Jabalpur districts of Madhya Pradesh in Central India. Over 85% were tribals of the Gond group. alpha-Thal, as -alpha 3.7/and -alpha 4.2/, and the nondeletional Koya Dora mutation were present at the combined frequency of 0.54. There were indications for the presence of other nondeletional types of alpha-thal. alpha-Globin gene triplications were not observed. Four of the six beta-thal alleles observed were in the tribal groups; two (G----C at codon 30 and G----A at IVS-I-1) were found for the first time. The simultaneous presence of an alpha-thal (-alpha/alpha alpha or -alpha/-alpha) greatly improved the clinical and hematological condition of the patients with Hb S-beta(+)-thal (IVS-I-5; G----C). The lower frequency of alpha-thal among the beta-thal heterozygotes (f = 0.32) may indicate that some of the beta-thal alleles in the tribal populations originated from an outside source. Forty-one subjects had SS; all but one had beta S with haplotype #31, while one chromosome had haplotype #17. The presence of an alpha-thal-2 (f = 0.53) in the SS patients did not affect hematological data. The Hb F levels varied between 7.5% and 42.5% with high G gamma values. No difference in Hb F level between males and females was observed. Lower Hb F levels were present in 10 SS patients with an alpha-thal-2 homozygosity (average 16% versus 23.5% for eight SS patients with alpha alpha/alpha alpha) suggesting a decreased formation of alpha gamma dimers in severe alpha chain deficiency. Several younger SS patients (less than 10 years) also had high Hb F levels (32-42%). Variations in the sequence at -530 of the beta-globin gene; i.e. in the so-called silencer sequence, were present in all beta S chromosomes with haplotype #31, but were not considered important for understanding the variability in the Hb F level. gamma-Globin gene deletions (gamma-thal) and triplications were not observed.
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta 30912-2100.
authors.forename: R B
authors.initials: RB
authors.lastname: Gupta
authors.forename: R S
authors.initials: RS
authors.lastname: Tiwary
authors.forename: P L
authors.initials: PL
authors.lastname: Pande
authors.forename: F
authors.initials: F
authors.lastname: Kutlar
authors.forename: C
authors.initials: C
authors.lastname: Oner
authors.forename: R
authors.initials: R
authors.lastname: Oner
authors.forename: T H
authors.initials: TH
authors.lastname: Huisman
mesh_terms: D000755:Anemia, Sickle Cell / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005006:Ethnicity / Q000235:genetics*; D005914:Globins / Q000235:genetics; D006453:Hemoglobinopathies / Q000453:epidemiology / Q000208:ethnology* / Q000235:genetics; D006455:Hemoglobins, Abnormal / Q000235:genetics*; D006801:Humans; D007194:India / Q000453:epidemiology; D008969:Molecular Sequence Data; D013789:Thalassemia / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics
chemical_list: D006455:Hemoglobins, Abnormal; D005914:Globins