Yemenite-Jewish families with Machado-Joseph disease (MJD/SCA3) share a recent common ancestor

• Type: Article in International Scientific Journal
• Date: 2019

Authors

Sharony, R (Author) Other; Sandra Martins (Author) FCUP; Costa, IPD (Author) Other; Zaltzman, R (Author) Other; Amorim, A (Author) FCUP; Sequeiros, J (Author) Other; Gordon, CR (Author) Other

Journal

Title: European Journal of Human Genetics

Vol. 27

Pages: 1731-1737

ISSN: 1018-4813

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 5 Citations

Scopus - 5 Citations

Other information

Authenticus ID: P-00Q-HXZ

DOI: 10.1038/s41431-019-0449-7

Abstract (EN): In 1994, a kindred from Yemen was described as the first Jewish family with Machado-Joseph disease (MJD/SCA3)(n) a dominant ataxia caused by the expansion of a (CAG)(n) above 61 repeats, in ATXN3. MJD is spread worldwide due to an ancient variant of Asian origin (the Joseph lineage). A second, more recent, independent expansion arose in a distinct haplotype (Machado lineage); other possible origins are still under study. We haplotyped 46 MJD patients and relatives, from 6 Israeli Yemenite families, and 100 normal chromosomes from that population, for 30 SNPs spreading 15 kb around the (CAG)(n, )and 8 STRs and 1 indel in the flanking regions. All six families shared an extended haplotype, showing no variants or recombination after a common origin, but differing in two SNPs (rs12895357 and rs12588287) from the Joseph lineage. To test for a new mutational origin in this population, we searched for the presence of that haplotype in Yemenite-Jewish controls. Only one (1%) normal (CAG)(32) allele showed an extended STR-haplotype genetically closer to MJD than normal haplotypes (genetic distance, D-A, 0.43 versus 0.53). That normal allele could be explained either by (1) the introduction of both normal and expanded alleles carrying this "Joseph-like" haplotype into the genetic pool of the Yemenite population; or by (2) a large contraction from the expanded CAG range. Based on the lack of STR diversity in MJD Yemenite-Jewish families, and on high frequency of this Joseph-like haplotype among African controls (23.2%), expanded alleles seem to have been introduced very recently (<400 years ago) from Africa.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 7