Variable β-globin haplotypes in Saudi β thalassemia population

Jameela Shinwari, Tahani Alshehri, Asma I. Tahir, Abdullah Al Jefri, Abdulkareem AlMomen, Dana Bakheet, Mohammad AlAnazi, Arjumand Warsy, Nada Al Tassan

Biochemistry Department, College of Science, King Saud University, Riyadh, KSA.
Department of Genetics, Research Centre, King Faisal Specialist Hospital & Research Centre, Riyadh, KSA.
Hematology Department, King Khalid University Hospital, King Saud University, Riyadh, KSA.
Pediatric Hematology/Oncology Department, King Faisal Specialist Hospital & Research Centre, Riyadh, KSA.

DOI: 10.4236/ojgen.2013.33019                

Abstract

Twenty two haplotypes were generated from a pool of 60 unrelated Saudi β thalassemia major patients using previously described restriction sites in the β globin gene. Linkage disequilibrium analysis of the polymorphic sites was also conducted, a few identified haplotypes were novel while the remainder was previously reported, haplotype1222212 was the most frequent haplotype in the study group and a strong linkage disequilibrium between two polymorphic restriction sites in these β thalassemia patients was uncovered.

Keywords

SNPs; Haplotype; Linkage Disequilibrium; Restriction Sites

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Jeffreys, A.J. (1979) DNA sequence variants in the G gamma-, A gamma-, delta-and beta-globin genes of man. Cell, 18, 1-10. doi:10.1016/0092-8674(79)90348-9
[2]	Clark, A.G. (2004) The role of haplotypes in candidate gene studies. Genetic Epidemiology, 27, 321-333. doi:10.1002/gepi.20025
[3]	Pirastu, M., Galanello, R., Doherty, M.A., Tuveri, T., Cao, A. and Kan, Y.W. (1987) The same beta-globin gene mutation is present on nine different beta-thalassemia chromosomes in a Sardinian population. The Proceedings of the National Academy of Sciences of the United States of America, 84, 2882-2885. doi:10.1073/pnas.84.9.2882
[4]	Orkin, S.H., Kazazian Jr., H.H., Antonarakis, S.E., Goff, S.C., Boehm, C.D., Sexton, J.P., Waber, P.G. and Giardina, P.J. (1982) Linkage of beta-thalassaemia mutations and beta-globin gene polymorphisms with DNA polymerphisms in human beta-globin gene cluster. Nature, 296, 627-631. doi:10.1038/296627a0
[5]	Labie, D. and Elion, J. (1996) Sequence polymorphisms of potential functional relevance in the beta-globin gene locus. Hemoglobin, 20, 85-101. doi:10.3109/03630269609027914
[6]	Flint, J., Harding, R.M., Boyce, A.J. and Clegg, J.B. (1998) The population genetics of the haemoglobinopathies. Baillière’s Clinical Haematology, 11, 1-51. doi:10.1016/S0950-3536(98)80069-3
[7]	Flint, J., Harding, R.M., Boyce, A.J. and Clegg, J.B. (1993) The population genetics of the haemoglobinopathies. Baillière’s Clinical Haematology, 6, 215-262. doi:10.1016/S0950-3536(05)80071-X
[8]	Weatherall, D.J., Clegg, J.B., Higgs, D.R. and Wood, W.G. (1989) The hemoglobinopathies. McGraw-Hill, New York. doi:10.3238/arztebl.2011.0532
[9]	Barrett, J.C., Fry, B., Maller, J. and Daly, M.J. (2005) Haploview: Analysis and visualization of LD and haplotype maps. Bioinformatics, 21, 263-265. doi:10.1093/bioinformatics/bth457
[10]	Weatherall, D.J. and Clegg, J.B. (1981) The Thalassaemia syndrome. 3rd Edition, Blackwell Scientific Publications, Oxford.
[11]	Long, J.C., Chakravarti, A., Boehm, C.D., Antonarakis, S. and Kazazian, H.H. (1990) Phylogeny of human betaglobin haplotypes and its implications for recent human evolution. American Journal of Physical Anthropology, 81, 113-130. doi:10.1002/ajpa.1330810112
[12]	Chen, L.Z., Easteal, S., Board, P.G. and Kirk, R.L. (1990) Evolution of beta-globin haplotypes in human populations. Molecular Biology and Evolution, 7, 423-437.
[13]	Kazazian, H.H. Jr., Orkin, S.H., Antonarakis, S.E., Sexton, J.P., Boehm, C.D., Goff, S.C. and Waber, P.G. (1984) Molecular characterization of seven beta-thalassemia mutations in Asian Indians. EMBO Journal, 3, 593-596.
[14]	Kruglyak, L. (1999) Genetic isolates: Separate but equal? The Proceedings of the National Academy of Sciences of the United States of America, 96, 1170-1172. doi:10.1073/pnas.96.4.1170