DNA methylation pattern in regions of the genome with inherited CNV
Abstract
The role of CNV in pathogenesis of intellectual disability and autism is significant. Nevertheless, in the analysis of CNV-associated diseases, the interpretation of pathogenically significant CNV remains a debatable issue, while the mechanisms of the phenotypic manifestation of inherited CNVs and their incomplete penetrance remain largely unclear. At present, the incomplete penetrance of CNV is explained mainly from the point of view of allelic interactions of various genetic variants. At the same time, the epigenetic mechanisms of gene expression regulation in the context of structural genome variations remain practically unexplored. The purpose of this study was to search for differentially methylated CpG sites located in regions with inherited CNV in families with mental retardation and autism. As a result, differential methylation of intragenic CpG sites of the IMMP2L gene in the family of a patient with intellectual disability and 7q31.1 microdeletion was identified. The data obtained indicate the possibility of the involvement of DNA methylation in the regulatory mechanisms of incomplete penetration of CNV-associated diseases.
About the Authors
N. A. Skryabin
Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences; National Research Tomsk State University
Russian Federation
Russian Federation
S. A. Vasiliev
Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences; National Research Tomsk State University
Russian Federation
Russian Federation
E. N. Tolmacheva
Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences; National Research Tomsk State University
Russian Federation
Russian Federation
A. R. Shorina
Novosibirsk Regional Children’s Clinical Psychoneurological Dispensary
Russian Federation
Russian Federation
R. R. Savchenko
Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences
Russian Federation
Russian Federation
A. A. Kashevarova
Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences; National Research Tomsk State University
Russian Federation
Russian Federation
I. N. Lebedev
Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences; National Research Tomsk State University
Russian Federation
Russian Federation
References
1. Hochstenbach R, Buizer-Voskamp JE, Vorstman JAS et al. Genome arrays for the detection of copy number variations in idiopathic mental retardation, idiopathic generalized epilepsy and neuropsychiatric disorders: Lessons for diagnostic workflow and research. Cytogenet Genome Res. 2011;135(3-4):174-202.
2. Persico AM, Napolioni V. Autism genetics. Behav Brain Research. 2013; 251:95-112.
3. Beckmann JS, Estivill X, Antonarakis SE. Copy number variants and genetic traits: closer to the resolution of phenotypic to genotypic variability. Nat Rev Genet. 2007;8(8):639-46.
4. Lee C, Scherer SW. The clinical context of copy number variation in the human genome. Expert Rev Mol Med. 2010;12(March):e8.
5. Smith AC, Suzuki M, Thompson R, et al. Maternal gametic transmission of translocations or inversions of human chromosome 11p15.5 results in regional DNA hypermethylation and downregulation of CDKN1C expression. Genomics. 2012;99(1):25-35.
6. Gimelli S, Capra V, Di Rocco M, et al. Interstitial 7q31.1 copy number variations disrupting IMMP2L gene are associated with a wide spectrum of neurodevelopmental disorders. Mol Cytogenet. 2014;7:54.
7. Bertelsen B, Melchior L, Jensen LR et al. Intragenic deletions affecting two alternative transcripts of the IMMP2L gene in patients with Tourette syndrome. Eur J Hum Genet. 2014;22(11):1283-1289.
8. Jjingo D, Conley AB, Yi SV et al. On the presence and role of human gene-body DNA methylation. Oncotarget. 2012;3(4):462-474.
Review
For citations:
Skryabin N.A., Vasiliev S.A., Tolmacheva E.N., Shorina A.R., Savchenko R.R., Kashevarova A.A., Lebedev I.N. DNA methylation pattern in regions of the genome with inherited CNV. Medical Genetics. 2017;16(12):27-30. (In Russ.)
Views:
704
Email this article 