التفاصيل البيبلوغرافية
| العنوان: |
Whole genome analyses reveal no pathogenetic single nucleotide or structural differences between monozygotic twins discordant for amyotrophic lateral sclerosis. |
| المؤلفون: |
Meltz Steinberg, Karyn, Nicholas, Thomas J., Koboldt, Daniel C., Yu, Bing, Mardis, Elaine, Pamphlett, Roger |
| المصدر: |
Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration; Sep2015, Vol. 16 Issue 5/6, p385-392, 8p |
| مصطلحات موضوعية: |
AMYOTROPHIC lateral sclerosis, DISEASES in twins, SINGLE nucleotide polymorphisms, LEUCOCYTES, NUCLEOTIDE sequence, GENOMICS, DIAGNOSIS, PATIENTS |
| مستخلص: |
The contribution of genetic and environmental factors to the pathogenesis of sporadic amyotrophic lateral sclerosis (ALS) remains unclear. To investigate the genetic component of the disease, we performed whole genome sequencing on ALS discordant monozygotic twins. Illumina whole genome sequencing on white blood cell DNA of five ALS-discordant monozygotic twin pairs (10 samples in total) yielded ∼30x coverage per individual. All single nucleotide variants, indels, and structural variants (copy number variants, inversions and translocations) were called and evaluated for functional consequence, evolutionary conservation, population frequency and overlap with known ALS associated variants and genes. Results showed that no validated discordant coding or regulatory single nucleotide variants or indels were found, and nor were any genome-wide discordant structural variants detected. Concordant variants of particular interest were: 1) two rare, highly-conserved heterozygous non-synonymous variants inSYT9andEWSR1,genes previously associated with ALS (out of 2044 rare heterozygous variants detected); 2) three rare homozygous missense variants; and 3) three novel copy number deletions that overlapped genes. In conclusion, no convincing coding or regulatory nucleotide or genome-wide structural differences were found between ALS discordant monozygotic twins. The results suggest that more work is needed to elucidate possible environmental, epigenetic, oligogenic and somatic genetic factors that could underlie susceptibility to sporadic ALS. [ABSTRACT FROM PUBLISHER] |
|
Copyright of Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
