Role of genetics in amyotrophic lateral sclerosis: a large cohort study in Chinese mainland population

BackgroundA large number of new causative and risk genes for amyotrophic lateral sclerosis (ALS) have been identified mostly in patients of European ancestry. In contrast, we know relatively little regarding the genetics of ALS in other ethnic populations. This study aims to provide a comprehensive analysis of the genetics of ALS in an unprecedented large cohort of Chinese mainland population and correlate with the clinical features of rare variants carriers.MethodsA total of 1587 patients, including 64 familial ALS (FALS) and 1523 sporadic ALS (SALS), and 1866 in-house controls were analysed by whole-exome sequencing and/or testing for G4C2 repeats in C9orf72. Forty-one ALS-associated genes were analysed.Findings155 patients, including 26 (40.6%) FALS and 129 (8.5%) SALS, carrying rare pathogenic/likely pathogenic (P/LP) variants of ALS causative genes were identified. SOD1 was the most common mutated gene, followed by C9orf72, FUS, NEK1, TARDBP and TBK1. By burden analysis, rare variants in SOD1, FUS and TARDBP contributed to the collective risk for ALS (p<2.5e-6) at the gene level, but at the allelic level TARDBP p.Gly294Val and FUS p.Arg521Cys and p.Arg521His were the most important single variants causing ALS. Clinically, P/LP variants in TARDBP and C9orf72 were associated with poor prognosis, in FUS linked with younger age of onset, and C9orf72 repeats tended to affect cognition.ConclusionsOur data provide essential information for understanding the genetic and clinical features of ALS in China and for optimal design of genetic testing and evaluation of disease prognosis.

Genetic Diversity and Population Structure of the Spring Orchid Cymbidium goeringii in Korean Distant Islands

The spring orchid (Cymbidium goeringii), found in northeast Asia, is one of the most popular and horticulturally important species of the orchid family. This study analyzed the genetic diversity and population structure of the spring orchid populations in the small islands and mainland South Korea using 11 microsatellite markers. The genetic diversities of spring orchid populations in the distant islands (Heuksan Island and Ulleung Island) were slightly lower than that of the mainland population (Yeonggwang-gun). The population structure in the mainland was genetically separated from the populations in the islands. The population of Ulleung Island, located in the eastern part of the Korean peninsula, was genetically closer to the populations from China and Japan than to the populations from Yeonggwang-gun and Heuksan Island, which are geographically close to China. These results imply that the populations of spring orchids distributed in Yeonggwang-gun and Heuksan Island appear not to be influenced by the yellow dust winds. As the first population genetic study of spring orchids distributed in small distant islands, our study will be useful for understanding the genetic diversity and population structure of isolated C. goeringii populations.