Strong linkage disequilibrium of a HbE variant with the (AT)9(T)5 repeat in the BP1 binding site upstream of the beta-globin gene in the Thai population.
A binding site for the repressor protein BP1, which contains a tandem (AT)x(T)y repeat, is located approximately 530 bp 5' to the human beta-globin gene (HBB). There is accumulating evidence that BP1 binds to the (AT)9(T)5 allele more strongly than to other alleles, thereby reducing the expression of HBB. In this study, we investigated polymorphisms in the (AT)x(T)y repeat in 57 individuals living in Thailand, including three homozygotes for the hemoglobin E variant (HbE; beta26Glu-->Lys), 22 heterozygotes, and 32 normal homozygotes. We found that (AT)9(T)5 and (AT)7(T)7 alleles were predominant in the studied population and that the HbE variant is in strong linkage disequilibrium with the (AT)9(T)5 allele, which can explain why the betaE chain is inefficiently synthesized compared to the normal betaA chain. Moreover, the mildness of the HbE disease compared to other hemoglobinopathies in Thai may be due, in part, to the presence of the (AT)9(T)5 repeat on the HbE chromosome. In addition, a novel (AC)n polymorphism adjacent to the (AT)x(T)y repeat (i.e., (AC)3(AT)7(T)5) was found through the variation screening in this study.
Ohashi
Jun
J
Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan. juno-tky@umin.ac.jp.|Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA. juno-tky@umin.ac.jp.
Naka
Izumi
I
Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
Patarapotikul
Jintana
J
Department of Microimmunology and Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Hananantachai
Hathairad
H
Department of Microimmunology and Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Brittenham
Gary
G
Department of Pediatrics and Medicine, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Looareesuwan
Sornchai
S
Department of Microimmunology and Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Clark
Andrew G
AG
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA.
Tokunaga
Katsushi
K
Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D004247:DNA / Q000235:genetics; D005787:Gene Frequency; D014644:Genetic Variation; D005914:Globins / Q000235:genetics; D006239:Haplotypes; D006446:Hemoglobin E / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D015810:Linkage Disequilibrium; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D012097:Repressor Proteins / Q000378:metabolism; D020080:Tandem Repeat Sequences; D013785:Thailand
D012097:Repressor Proteins; D005914:Globins; D004247:DNA; D006446:Hemoglobin E