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

• Published in: Human genetics Vol. 128; no. 3; pp. 261 - 267
• Main Authors: Zelinger, Lina, Greenberg, Alex, Kohl, Susanne, Banin, Eyal, Sharon, Dror
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Berlin/Heidelberg : Springer-Verlag 01.09.2010; Springer-Verlag; Springer; Springer Nature B.V
• Subjects: Alleles; Analysis; Arabs - genetics; Biomedical and Life Sciences; Biomedicine; Color blindness; Color Vision Defects - genetics; Consanguinity; Cyclic Nucleotide-Gated Cation Channels - genetics; Founder Effect; Gene Frequency; Gene Function; Genes; Genetic aspects; Genomics; Haplotypes; Homozygote; Human Genetics; Humans; Islam; Israel; Jews; Jews - genetics; Metabolic Diseases; Middle East; Molecular Medicine; Muslims; Original Investigation; Point Mutation; Polymorphism, Single Nucleotide; Time Factors; Middle East; Israel; Single Nucleotide Polymorphism Analysis; Jewish Patient; Jewish Population; Single Nucleotide Polymorphism Marker; Founder Mutation
• ISSN: 0340-6717; 1432-1203
• DOI: 10.1007/s00439-010-0846-z

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.