gamma-Globin gene triplication and quadruplication in Japanese newborns. Evidence for a decreased in vivo expression of the 3'-A gamma-globin gene.
Cord blood samples of 113 Japanese babies from Kurashiki, Japan, were analyzed for the presence of possible modifications in gamma-globin gene arrangements and for changes in the relative quantities of the gamma chains G gamma, A gamma, and its variant A gamma T. As many as 9 babies had the gamma-globin gene triplication, one a gamma-globin gene quadruplication, and two a gamma-globin gene deletion. The triplication and quadruplication involved cross-overs within the G gamma- and A gamma-globin genes resulting in a hybrid gene with the 5'-segment being derived from the A gamma and the 3'-segment from the G gamma-globin gene (-AG gamma-). The G gamma value of the 9 babies with the -G gamma-AG gamma-A gamma-globin gene arrangement averaged approximately 80% and that of the baby with -G gamma-AG gamma-AG gamma-A gamma- was 78%. Four of the 9 babies with the triplication and the baby with the quadruplication had an A gamma T mutation in trans; in these babies, the A gamma chain level (from the A gamma-globin gene in 3'-position in the tri- and quadruplication arrangements) was decreased to about one-third and one-sixth of the level observed in the simple A gamma T heterozygote. This observation supports the suggestion that transcription beginning at the 5'-gamma-globin gene interferes with that of the 3'-gamma-globin gene.
Harano
K
K
Harano
T
T
Kutlar
F
F
Huisman
T H
TH
D044466:Asian People; D002869:Chromosome Aberrations; D004262:DNA Restriction Enzymes; D005319:Fetal Hemoglobin / Q000235:genetics; D005786:Gene Expression Regulation; D005796:Genes; D005914:Globins / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D007564:Japan; D009693:Nucleic Acid Hybridization; D014158:Transcription, Genetic
D005914:Globins; D005319:Fetal Hemoglobin; D004262:DNA Restriction Enzymes