Is the High Frequency of Machado-Joseph Disease in China Due to New Mutational Origins?

Li, Tianjiao and Martins, Sandra and Peng, Yun and Wang, Puzhi and Hou, Xiaocan and Chen, Zhao and Wang, Chunrong and Tang, Zhaoli and Qiu, Rong and Chen, Chao and Hu, Zhengmao and Xia, Kun and Tang, Beisha and Sequeiros, Jorge and Jiang, Hong (2019) Is the High Frequency of Machado-Joseph Disease in China Due to New Mutational Origins? Frontiers in Genetics, 9. ISSN 1664-8021

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Abstract

Machado-Joseph disease (MJD, also known as spinocerebellar ataxia 3 or SCA3) is the most common dominant ataxia worldwide, with an overall average prevalence of 1–5/100,000. To this date, two major ancestral lineages have been found throughout the world. In China, the relative frequency of MJD among the SCAs reaches as high as 63%, however, little is known about its mutational origin in this country. We analyzed 50 families with MJD patients in two or more generations to study the hypothesis that new mutational events have occurred in this population. Haplotypes based on 20 SNPs have shown new genetic backgrounds segregating with MJD mutations in our cohort from China. We found the “Joseph-derived” lineage (Joseph lineage with a G variant in rs56268847) to be very common among Chinese MJD patients. Moreover, we estimated the time for the origin of this MJD SNP background based on STR diversity flanking the (CAG)n of ATXN3. It was surprising to find that the Chinese MJD population originated from 8,000 to 17,000 years ago, far earlier than the previous literature reports, which will be an important evidence to explain the origin, spread and founder effects of MJD.

Item Type: Article
Subjects: Open Archive Press > Medical Science
Depositing User: Unnamed user with email support@openarchivepress.com
Date Deposited: 10 Feb 2023 09:53
Last Modified: 24 Jun 2024 04:23
URI: http://library.2pressrelease.co.in/id/eprint/402

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