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


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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  1. Bandelt HJ, Forster P, Rohl A (1999) Median-joining networks for inferring intraspecific phylogenies. Mol Biol Evol 16:37–48

    CAS  PubMed  Google Scholar 

  2. Bercovich D, Elimelech A, Yardeni T, Korem S, Zlotogora J, Gal N, Goldstein N, Vilensky B, Segev R, Avraham S, Loewenthal R, Schwartz G, Anikster Y (2008) A mutation analysis of the phenylalanine hydroxylase (PAH) gene in the Israeli population. Ann Hum Genet 72:305–309

    Article  CAS  PubMed  Google Scholar 

  3. Bonne-Tamir B, Johnson MJ, Natali A, Wallace DC, Cavalli-Sforza LL (1986) Human mitochondrial DNA types in two Israeli populations—a comparative study at the DNA level. Am J Hum Genet 38:341–351

    CAS  PubMed  Google Scholar 

  4. Briggs CE, Rucinski D, Rosenfeld PJ, Hirose T, Berson EL, Dryja TP (2001) Mutations in ABCR (ABCA4) in patients with Stargardt macular degeneration or cone-rod degeneration. Invest Ophthalmol Vis Sci 42:2229–2236

    CAS  PubMed  Google Scholar 

  5. El-Shanti H, Abdel Majeed H, El-Khateeb M (2006) Familial Mediterranean fever in Arabs. Lancet 367:1016–1024

    Article  PubMed  Google Scholar 

  6. Goldschmidt E, Ronen A, Ronen I (1960) Changing marriage system in the Jewish communities in Israel. Ann Hum Genet 24:191–204

    Article  CAS  PubMed  Google Scholar 

  7. Haider NB, Jacobson SG, Cideciyan AV, Swiderski R, Streb LM, Searby C, Beck G, Hockey R, Hanna DB, Gorman S, Duhl D, Carmi R, Bennett J, Weleber RG, Fishman GA, Wright AF, Stone EM, Sheffield VC (2000) Mutation of a nuclear receptor gene, NR2E3, causes enhanced S cone syndrome, a disorder of retinal cell fate. Nat Genet 24:127–131

    Article  CAS  PubMed  Google Scholar 

  8. Hammer MF, Redd AJ, Wood ET, Bonner MR, Jarjanazi H, Karafet T, Santachiara-Benerecetti S, Oppenheim A, Jobling MA, Jenkins T, Ostrer H, Bonne-Tamir B (2000) Jewish and Middle Eastern non-Jewish populations share a common pool of Y-chromosome biallelic haplotypes. Proc Natl Acad Sci USA 97:6769–6774

    Article  CAS  PubMed  Google Scholar 

  9. Jaber L, Bailey-Wilson JE, Haj-Yehia M, Hernandez J, Shohat M (1994) Consanguineous matings in an Israeli-Arab community. Arch Pediatr Adolesc Med 148:412–415

    CAS  PubMed  Google Scholar 

  10. Kohl S, Marx T, Giddings I, Jagle H, Jacobson SG, Apfelstedt-Sylla E, Zrenner E, Sharpe LT, Wissinger B (1998) Total colour blindness is caused by mutations in the gene encoding the alpha-subunit of the cone photoreceptor cGMP-gated cation channel. Nat Genet 19:257–259

    Article  CAS  PubMed  Google Scholar 

  11. Lerer I, Cohen S, Chemke M, Sanilevich A, Rivlin J, Golan A, Yahav J, Friedman A, Abeliovich D (1990) The frequency of the delta F508 mutation on cystic fibrosis chromosomes in Israeli families: correlation to CF haplotypes in Jewish communities and Arabs. Hum Genet 85:416–417

    Article  CAS  PubMed  Google Scholar 

  12. Nebel A, Filon D, Weiss DA, Weale M, Faerman M, Oppenheim A, Thomas MG (2000) High-resolution Y chromosome haplotypes of Israeli and Palestinian Arabs reveal geographic substructure and substantial overlap with haplotypes of Jews. Hum Genet 107:630–641

    Article  CAS  PubMed  Google Scholar 

  13. Nebel A, Filon D, Brinkmann B, Majumder PP, Faerman M, Oppenheim A (2001) The Y chromosome pool of Jews as part of the genetic landscape of the Middle East. Am J Hum Genet 69:1095–1112

    Article  CAS  PubMed  Google Scholar 

  14. Niell BL, Long JC, Rennert G, Gruber SB (2003) Genetic anthropology of the colorectal cancer-susceptibility allele APC I1307 K: evidence of genetic drift within the Ashkenazim. Am J Hum Genet 73:1250–1260

    Article  CAS  PubMed  Google Scholar 

  15. Nishiguchi KM, Sandberg MA, Gorji N, Berson EL, Dryja TP (2005) Cone cGMP-gated channel mutations and clinical findings in patients with achromatopsia, macular degeneration, and other hereditary cone diseases. Hum Mutat 25:248–258

    Article  CAS  PubMed  Google Scholar 

  16. Peretz H, Mulai A, Usher S, Zivelin A, Segal A, Weisman Z, Mittelman M, Lupo H, Lanir N, Brenner B, Shpilberg O, Seligsohn U (1997) The two common mutations causing factor XI deficiency in Jews stem from distinct founders: one of ancient Middle Eastern origin and another of more recent European origin. Blood 90:2654–2659

    CAS  PubMed  Google Scholar 

  17. Reeve JP, Rannala B (2002) DMLE+: Bayesian linkage disequilibrium gene mapping. Bioinformatics 18:894–895

    Article  CAS  PubMed  Google Scholar 

  18. Sereth H, Shoshani T, Bashan N, Kerem BS (1993) Extended haplotype analysis of cystic fibrosis mutations and its implications for the selective advantage hypothesis. Hum Genet 92:289–295

    Article  CAS  PubMed  Google Scholar 

  19. Shahin H, Walsh T, Sobe T, Lynch E, King MC, Avraham KB, Kanaan M (2002) Genetics of congenital deafness in the Palestinian population: multiple connexin 26 alleles with shared origins in the Middle. East Hum Genet 110:284–289

    Article  CAS  Google Scholar 

  20. Sharon D, Sandberg MA, Caruso RC, Berson EL, Dryja TP (2003) Shared mutations in NR2E3 in enhanced S-cone syndrome, Goldmann-Favre syndrome, and many cases of clumped pigmentary retinal degeneration. Arch Ophthalmol 121:1316–1323

    Article  CAS  PubMed  Google Scholar 

  21. Webster AR, Heon E, Lotery AJ, Vandenburgh K, Casavant TL, Oh KT, Beck G, Fishman GA, Lam BL, Levin A, Heckenlively JR, Jacobson SG, Weleber RG, Sheffield VC, Stone EM (2001) An analysis of allelic variation in the ABCA4 gene. Invest Ophthalmol Vis Sci 42:1179–1189

    CAS  PubMed  Google Scholar 

  22. Zlotogora J (2002) What is the birth defect risk associated with consanguineous marriages? Am J Med Genet 109:70–71

    Article  PubMed  Google Scholar 

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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).

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