AUTHOR=Li Tianjiao , Martins Sandra , Peng Yun , Wang Puzhi , Hou Xiaocan , Chen Zhao , Wang Chunrong , Tang Zhaoli , Qiu Rong , Chen Chao , Hu Zhengmao , Xia Kun , Tang Beisha , Sequeiros Jorge , Jiang Hong TITLE=Is the High Frequency of Machado-Joseph Disease in China Due to New Mutational Origins? JOURNAL=Frontiers in Genetics VOLUME=9 YEAR=2019 URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2018.00740 DOI=10.3389/fgene.2018.00740 ISSN=1664-8021 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.