Hum Genet (2010) 128:261–267 DOI 10.1007/s00439-010-0846-z 123 ORIGINAL INVESTIGATION An ancient autosomal haplotype bearing a rare achromatopsia-causing founder mutation is shared among Arab Muslims and Oriental Jews Lina Zelinger · Alex Greenberg · Susanne Kohl · Eyal Banin · Dror Sharon Received: 6 April 2010 / Accepted: 2 June 2010 / Published online: 13 June 2010  Springer-Verlag 2010 Abstract Numerous cultural aspects, mainly based on historical records, suggest a common origin of the Middle- Eastern Arab Muslim and Jewish populations. This is sup- ported, to some extent, by Y-chromosome haplogroup anal- ysis 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 popula- tions have been reported. Here, we report of a rare achro- matopsia-causing CNGA3 mutation (c.1585G>A) presents in both Arab Muslim and Oriental Jewish patients. A haplo- type analysis of c.1585G>A-bearing chromosomes from Middle Eastern and European origins revealed a shared Muslim–Jewish haplotype, which is diVerent from those detected in European patients, indicating a recurrent muta- tion stratiWed by a Jewish–Muslim founder eVect. Compre- hensive whole-genome haplotype analysis using 250 K single nucleotide polymorphism arrays revealed a large homozygous region of »11 Mbp shared by both Arab Mus- lim 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 microsatel- lite 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 Xow 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. Introduction The Arab Muslim and Jewish populations in Israel and the Palestinian territories are speculated, mainly by historical records, to originate from a single founder population, with an estimated divergence time of a few thousand years. Sup- porting the common origin are many shared aspects between the two languages (Arabic and Hebrew) and reli- gions (Islam and Judaism). Aiming to provide scientiWc evidence for the common origin of these populations, a series of genetic studies have been conducted, mainly using genetic markers on the Y chromosome (Hammer et al. 2000; Nebel et al. 2000, 2001), mitochondrial DNA analy- sis (Bonne-Tamir et al. 1986), and haplotyping of speciWc genomic regions (Niell et al. 2003; Peretz et al. 1997; Sha- hin et al. 2002). In most of these studies, the frequencies of diVerent haplotypes that are common in many populations worldwide have been determined in Middle-Eastern popu- lations followed by construction of phylogenetic trees. While these studies, and mainly the Y-chromosome haplo- group analysis, provided valuable data regarding migration of individuals, they suVer from a relatively low number of genotyped markers (up to 19) and the inability to distinguish Electronic supplementary material The online version of this article (doi:10.1007/s00439-010-0846-z) contains supplementary material, which is available to authorized users. L. Zelinger · A. Greenberg · E. Banin · D. Sharon (&) Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel e-mail: dror.sharon1@gmail.com S. Kohl Molecular Genetics Laboratory, Centre for Ophthalmology, Institute for Ophthalmic Research, Tübingen University, Tübingen, Germany