| Title | C9orf72 hexanucleotide repeat expansions in Chinese sporadic amyotrophic lateral sclerosis |
| Authors | He, Ji Tang, Lu Benyamin, Beben Shah, Sonia Hemani, Gib Liu, Rong Ye, Shan Liu, Xiaolu Ma, Yan Zhang, Huagang Cremin, Katie Leo, Paul Wray, Naomi R. Visscher, Peter M. Xu, Huji Brown, Matthew A. Bartlett, Perry F. Mangelsdorf, Marie Fan, Dongsheng |
| Affiliation | Peking Univ, Hosp 3, Dept Neurol, Beijing 100871, Peoples R China. Univ Queensland, Queensland Brain Inst, St Lucia, Qld, Australia. Univ Queensland, Diamantina Inst, Translat Res Inst, Woolloongabba, Qld, Australia. Second Mil Med Univ, Shanghai Changzheng Hosp, Dept Rheumatol & Immunol, Shanghai, Peoples R China. 49 North Garden Rd, Beijing 100191, Peoples R China. |
| Keywords | Amyotrophic lateral sclerosis C9orf72 gene Hexanucleotide repeat expansion CpG methylation Chinese population ALS GENE POPULATIONS MUTATIONS COHORT FTD |
| Issue Date | 2015 |
| Publisher | NEUROBIOLOGY OF AGING |
| Citation | NEUROBIOLOGY OF AGING.2015,36,(9). |
| Abstract | A hexanucleotide repeat expansion (HRE) in the C9orf72 gene has been identified as the most common mutation in amyotrophic lateral sclerosis (ALS) among Caucasian populations. We sought to comprehensively evaluate genetic and epigenetic variants of C9orf72 and the contribution of the HRE in Chinese ALS cases. We performed fragment-length and repeat-primed polymerase chain reaction to determine GGGGCC copy number and expansion within the C9orf72 gene in 1092 sporadic ALS (sALS) and 1062 controls from China. We performed haplotype analysis of 23 single-nucleotide polymorphisms within and surrounding C9orf72. The C9orf72 HRE was found in 3 sALS patients (0.3%) but not in control subjects (p = 0.25). For 2 of the cases with the HRE, genotypes of 8 single-nucleotide polymorphisms flanking the HRE were inconsistent with the haplotype reported to be strongly associated with ALS in Caucasian populations. For these 2 individuals, we found hypermethylation of the CpG island upstream of the repeat, an observation not detected in other sALS patients (p < 10(-8)) or controls. The detailed analysis of the C9orf72 locus in a large cohort of Chinese samples provides robust evidence that may not be consistent with a single Caucasian founder event. Both the Caucasian and Chinese haplotypes associated with HRE were highly associated with repeat lengths >8 repeats implying that both haplotypes may confer instability of repeat length. (C) 2015 Elsevier Inc. All rights reserved. |
| URI | http://hdl.handle.net/20.500.11897/416972 |
| ISSN | 0197-4580 |
| DOI | 10.1016/j.neurobiolaging.2015.06.002 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 第三医院 |
