Evolution of a genetic disease in an ethnic isolate: beta-thalassemia in the Jews of Kurdistan.

• DOI: 10.1073/pnas.88.1.310
• Publication Date: 2006-05-31T08:01:25Z
• Authors: D Rund; T Cohen; D Filon; C E Dowling; T C Warren; I Barak; E Rachmilewitz; H H Kazazian; A Oppenheim
• Keywords: Transversion; Founder effect; Beta thalassemia

beta-Thalassemia is a hereditary disease caused by any of 90 different point mutations in the beta-globin gene. Specific populations generally carry small number mutations, most common which are those that widely distributed regionally. The present study constitutes an extensive molecular characterization this small, highly inbred ethnic group with high incidence beta-thalassemia--the Jews Kurdistan. An unusual mutational diversity was observed. In 42 sibships 13 were identified, 3 newly discovered: C----A transversion at -88 to cap site, frameshift codon 36/37, and A----G transition polyadenylylation signal. Four unique Kurdish have not been discovered other population. A fifth found outside only Iranian from Khuzistan, region bordering Two-thirds mutant chromosomes Jews. We traced origin specific geographic regions within This information, supported haplotype analysis, suggests thalassemia central Kurdistan (northern Iraq) has evolved primarily multiple events. Turkish Kurdistan, primary mechanism genetic admixture local founder effect appears be partly responsible. conclude several evolutionary mechanisms contributed evolution beta-thalassemia isolate.