title: Four categories of gamma-globin gene triplications: DNA sequence comparison of low G gamma and high G gamma triplications.
abstract: The human fetal gamma chains are produced by closely linked G gamma and A gamma genes, and unequal crossing over between them leads to gamma gene deletions and triplications. Nine gamma gene triplications from seven ethnic groups were analyzed for G gamma and hemoglobin F (Hb F) values of heterozygotes and for the presence of polymorphic XmnI restriction sites 5' to the gamma genes. Four categories of triplication were found: I had low G gamma and low Hb F values and lacked XmnI sites 5' to the three gamma genes [---]. II had high G gamma and slightly elevated Hb F values but was also [---]. III was similar to II, except that XmnI was [+--]. IV had very high G gamma and slightly elevated Hb F values, and XmnI was [++-]. One case each of triplications I and IV were cloned into Charon 35. For both, the two 5' gamma gene code for G gamma chain, while the 3' gamma gene codes for A gamma chain. DNA sequencing showed that the unequal crossover occurred between 472 and 398 base pairs (bp) 5' to the gamma gene Cap sites (-472 and -398) for the type IV triplication and between -271 and codon 136 for the type I triplication. In addition, type I had a 4-bp deletion of AGCA from -225 to -222. The high G gamma values of the type IV triplication are explained by its -G gamma-G gamma-A gamma-gene arrangement and the XmnI sites 5' to the G gamma genes. We hypothesize that the low G gamma value of the type I triplication, which is also -G gamma-G gamma-A gamma-, is due to inactivation of the middle G gamma gene by the AGCA deletion at -225 to -222.
authors.affiliation: Department of Cell and Molecular Biology, Medical College of Georgia, Augusta 30912.
authors.forename: J Z
authors.initials: JZ
authors.lastname: Liu
authors.forename: J G
authors.initials: JG
authors.lastname: Gilman
authors.forename: Q
authors.initials: Q
authors.lastname: Cao
authors.forename: I
authors.initials: I
authors.lastname: Bakioglu
authors.forename: T H
authors.initials: TH
authors.lastname: Huisman
mesh_terms: D000328:Adult; D001483:Base Sequence; D002648:Child; D004247:DNA / Q000032:analysis*; D005260:Female; D005914:Globins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D005810:Multigene Family
chemical_list: D005914:Globins; D004247:DNA