title: An unexpectedly high frequency of heterozygosity for alpha-thalassemia in Ashkenazi Jews.
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.
authors.affiliation: Hematology Department, Hebrew University and Hadassah Medical School, Jerusalem, Israel IL91120. rund@cc.huji.ac.il
authors.forename: Deborah
authors.initials: D
authors.lastname: Rund
authors.forename: Dvora
authors.initials: D
authors.lastname: Filon
authors.forename: Naomi
authors.initials: N
authors.lastname: Jackson
authors.forename: Nava
authors.initials: N
authors.lastname: Asher
authors.forename: Varda
authors.initials: V
authors.lastname: Oron-Karni
authors.forename: Tomasz
authors.initials: T
authors.lastname: Sacha
authors.forename: Sylwia
authors.initials: S
authors.lastname: Czekalska
authors.forename: Ariella
authors.initials: A
authors.lastname: Oppenheim
mesh_terms: D018703:Founder Effect; D017353:Gene Deletion; D005787:Gene Frequency; D006580:Genetic Carrier Screening; D040961:Genetic Drift; D008040:Genetic Linkage; D006579:Heterozygote; D006801:Humans; D007585:Jews / Q000235:genetics; D017720:Molecular Epidemiology; D012641:Selection, Genetic; D017085:alpha-Thalassemia / Q000453:epidemiology / Q000208:ethnology* / Q000235:genetics*