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An ancient autosomal haplotype bearing a rare achromatopsia-causing founder mutation is shared among Arab Muslims and Oriental Jews

Abstract

Numerous cultural aspects, mainly based on historical records, suggest a common origin of the Middle-Eastern Arab Muslim and Jewish populations. This is supported, to some extent, by Y-chromosome haplogroup analysis of Middle-Eastern and European samples. Up to date, no genomic regions that are shared among Arab Muslim and Jewish chromosomes and are unique to these populations have been reported. Here, we report of a rare achromatopsia-causing CNGA3 mutation (c.1585G>A) presents in both Arab Muslim and Oriental Jewish patients. A haplotype analysis of c.1585G>A-bearing chromosomes from Middle Eastern and European origins revealed a shared Muslim–Jewish haplotype, which is different from those detected in European patients, indicating a recurrent mutation stratified by a Jewish–Muslim founder effect. Comprehensive whole-genome haplotype analysis using 250 K single nucleotide polymorphism arrays revealed a large homozygous region of ~11 Mbp shared by both Arab Muslim and Oriental Jewish chromosomes. A subsequent microsatellite analysis of a 21.5 cM interval including CNGA3 and the adjacent chromosome 2 centromere revealed a unique and extremely rare haplotype associated with the c.1585G>A mutation. The age of the shared c.1585G>A mutation was calculated using the microsatellite genotyping data to be about 200 generations ago. A similar analysis of mutation age based on the Arab Muslim data alone showed that the mutation was unlikely to be the product of a recent gene flow event. The data present here demonstrate a large (11 Mbp) genomic region that is likely to originate from an ancient common ancestor of Middle-Eastern Arab Muslims and Jews who lived approximately 5,000 years ago.

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Acknowledgments

We thank the patients and their families for their participation in the study, Prof. Bernd Wissinger, Dr. Marina Faerman and Prof. Moshe Sharon for advice, and Liat Ben-Avi and Dr. Israela Lerer for technical support. This work was supported by the Foundation Fighting Blindness (FFB-Grant number BR-GE-0607-0395-HUJ); the Chief Scientist Office of the Israeli Ministry of Health (Grant number 3000003241); and the Yedidut research grant.

We declare that the experiments were in compliance with the Helsinki Declaration and were approved by the Institutional Helsinki committee.

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The authors declare that they have no conflict of interest.

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Correspondence to Dror Sharon.

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Zelinger, L., Greenberg, A., Kohl, S. et al. An ancient autosomal haplotype bearing a rare achromatopsia-causing founder mutation is shared among Arab Muslims and Oriental Jews. Hum Genet 128, 261–267 (2010). https://doi.org/10.1007/s00439-010-0846-z

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Keywords

  • Single Nucleotide Polymorphism Marker
  • Jewish Population
  • Founder Mutation
  • Single Nucleotide Polymorphism Analysis
  • Jewish Patient