Genomic copy number variation analysis in multiple system atrophy
Abstract Genomic variation includes single-nucleotide variants, small insertions or deletions (indels), and copy number variants (CNVs). CNVs affect gene expression by altering the genome structure and transposable elements within a region. CNVs are greater than 1 kb in size; hence, CNVs can produce...
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BMC
2017-11-01
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| Series: | Molecular Brain |
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| Online Access: | http://link.springer.com/article/10.1186/s13041-017-0335-6 |
| _version_ | 1818544599641096192 |
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| author | Yuka Hama Masataka Katsu Ichigaku Takigawa Ichiro Yabe Masaaki Matsushima Ikuko Takahashi Takayuki Katayama Jun Utsumi Hidenao Sasaki |
| author_facet | Yuka Hama Masataka Katsu Ichigaku Takigawa Ichiro Yabe Masaaki Matsushima Ikuko Takahashi Takayuki Katayama Jun Utsumi Hidenao Sasaki |
| author_sort | Yuka Hama |
| collection | DOAJ |
| description | Abstract Genomic variation includes single-nucleotide variants, small insertions or deletions (indels), and copy number variants (CNVs). CNVs affect gene expression by altering the genome structure and transposable elements within a region. CNVs are greater than 1 kb in size; hence, CNVs can produce more variation than can individual single-nucleotide variations that are detected by next-generation sequencing. Multiple system atrophy (MSA) is an α-synucleinopathy adult-onset disorder. Pathologically, it is characterized by insoluble aggregation of filamentous α-synuclein in brain oligodendrocytes. Generally, MSA is sporadic, although there are rare cases of familial MSA. In addition, the frequencies of the clinical phenotypes differ considerably among countries. Reports indicate that genetic factors play roles in the mechanisms involved in the pathology and onset of MSA. To evaluate the genetic background of this disorder, we attempted to determine whether there are differences in CNVs between patients with MSA and normal control subjects. We found that the number of CNVs on chromosomes 5, 22, and 4 was increased in MSA; 3 CNVs in non-coding regions were considered risk factors for MSA. Our results show that CNVs in non-coding regions influence the expression of genes through transcription-related mechanisms and potentially increase subsequent structural alterations of chromosomes. Therefore, these CNVs likely play roles in the molecular mechanisms underlying MSA. |
| first_indexed | 2024-12-11T22:50:36Z |
| format | Article |
| id | doaj.art-2fcde5f2d7ed4c07bd06dcee62d07bf7 |
| institution | Directory Open Access Journal |
| issn | 1756-6606 |
| language | English |
| last_indexed | 2024-12-11T22:50:36Z |
| publishDate | 2017-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Brain |
| spelling | doaj.art-2fcde5f2d7ed4c07bd06dcee62d07bf72022-12-22T00:47:28ZengBMCMolecular Brain1756-66062017-11-0110111110.1186/s13041-017-0335-6Genomic copy number variation analysis in multiple system atrophyYuka Hama0Masataka Katsu1Ichigaku Takigawa2Ichiro Yabe3Masaaki Matsushima4Ikuko Takahashi5Takayuki Katayama6Jun Utsumi7Hidenao Sasaki8Department of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido UniversityDepartment of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido UniversityGraduate School of Information Science and Technology, Hokkaido UniversityDepartment of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido UniversityDepartment of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido UniversityDepartment of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido UniversityDivision of Neurology, First Department of Internal Medicine, Asahikawa Medical UniversityDepartment of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido UniversityDepartment of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido UniversityAbstract Genomic variation includes single-nucleotide variants, small insertions or deletions (indels), and copy number variants (CNVs). CNVs affect gene expression by altering the genome structure and transposable elements within a region. CNVs are greater than 1 kb in size; hence, CNVs can produce more variation than can individual single-nucleotide variations that are detected by next-generation sequencing. Multiple system atrophy (MSA) is an α-synucleinopathy adult-onset disorder. Pathologically, it is characterized by insoluble aggregation of filamentous α-synuclein in brain oligodendrocytes. Generally, MSA is sporadic, although there are rare cases of familial MSA. In addition, the frequencies of the clinical phenotypes differ considerably among countries. Reports indicate that genetic factors play roles in the mechanisms involved in the pathology and onset of MSA. To evaluate the genetic background of this disorder, we attempted to determine whether there are differences in CNVs between patients with MSA and normal control subjects. We found that the number of CNVs on chromosomes 5, 22, and 4 was increased in MSA; 3 CNVs in non-coding regions were considered risk factors for MSA. Our results show that CNVs in non-coding regions influence the expression of genes through transcription-related mechanisms and potentially increase subsequent structural alterations of chromosomes. Therefore, these CNVs likely play roles in the molecular mechanisms underlying MSA.http://link.springer.com/article/10.1186/s13041-017-0335-6Genomic DNACopy number variationMultiple system atrophyArray-comparative genome hybridization |
| spellingShingle | Yuka Hama Masataka Katsu Ichigaku Takigawa Ichiro Yabe Masaaki Matsushima Ikuko Takahashi Takayuki Katayama Jun Utsumi Hidenao Sasaki Genomic copy number variation analysis in multiple system atrophy Molecular Brain Genomic DNA Copy number variation Multiple system atrophy Array-comparative genome hybridization |
| title | Genomic copy number variation analysis in multiple system atrophy |
| title_full | Genomic copy number variation analysis in multiple system atrophy |
| title_fullStr | Genomic copy number variation analysis in multiple system atrophy |
| title_full_unstemmed | Genomic copy number variation analysis in multiple system atrophy |
| title_short | Genomic copy number variation analysis in multiple system atrophy |
| title_sort | genomic copy number variation analysis in multiple system atrophy |
| topic | Genomic DNA Copy number variation Multiple system atrophy Array-comparative genome hybridization |
| url | http://link.springer.com/article/10.1186/s13041-017-0335-6 |
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