Abstract
alpha-Thalassemia is among the world's most common single gene disorders, which is most prevalent in the malaria belt. This geographic distribution has been attributed to a selective advantage of heterozygotes against this disease. Unexpectedly, we have found a high frequency of heterozygosity for deletional alpha-thalassemia (-alpha3.7) in Ashkenazi Jews (carrier frequency of 7.9%, allele frequency of 0.04). This population has resided in temperate climates for many centuries and was therefore not subjected to malarial selection pressure. In comparison, heterozygosity for beta-thalassemia, which is highly subject to malarial selection pressure, is very low (estimated <0.1%) in this group. It is possible that founder effect and genetic drift have contributed to the high frequency of deletional alpha-thalassemia in Ashkenazim, as may occur in closed populations. Alternatively, we hypothesize that positive selection pressure for an as yet unknown linked allele on chromosome 16 may be a significant factor leading to this high frequency.
References
Dec 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·E BeutlerC West
Jan 1, 1990·Annals of the New York Academy of Sciences·D R HiggsJ P Bennett
Feb 1, 1989·Human Genetics·A NovellettoL Terrenato
Jan 1, 1987·Acta Haematologica·A V HillJ B Clegg
Jun 19, 1986·Nature·J FlintA J Boyce
Jun 1, 1972·Clinical Pediatrics·O M RennertD Lapointe
Feb 1, 1995·Nature Genetics·A G Motulsky
Jan 1, 1993·Human Mutation·A OppenheimD Rund
Mar 1, 1993·Baillière's Clinical Haematology·S L Thein
Oct 10, 1996·Nature·L H Miller
Mar 1, 1997·Human Genetics·M FicheraA Ragusa
May 1, 1997·British Journal of Haematology·B VetterA E Kulozik
Sep 1, 1997·Human Genetics·K L HarteveldL F Bernini
Feb 7, 1998·Proceedings of the National Academy of Sciences of the United States of America·S J AllenD J Weatherall
Aug 6, 1998·American Journal of Hematology·V Oron-KarniD Rund
Sep 23, 1998·Human Mutation·M HorowitzN Eyal
May 13, 1999·Tropical Medicine & International Health : TM & IH·F P MockenhauptU Bienzle
Jan 22, 2013·Journal of Thrombosis and Haemostasis : JTH·H PeretzU Seligsohn
Citations
Oct 5, 2006·American Journal of Public Health·Sherry I Brandt-RaufSheila M Rothman
Oct 26, 2016·European Journal of Medical Genetics·Adir ShaulovDeborah Rund
Feb 6, 2017·European Journal of Haematology·Oded GiladHannah Tamary