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A clear bias in parental origin of de novo pathogenic CNVs related to intellectual disability, developmental delay and multiple congenital anomalies
Copy number variation (CNV) is of great significance in human evolution and disorders. Through tracing the parent-of-origin of de novo pathogenic CNVs, we are expected to investigate the relative contributions of germline genomic stability on reproductive health. In our study, short tandem repeat (S...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5359547/ https://www.ncbi.nlm.nih.gov/pubmed/28322228 http://dx.doi.org/10.1038/srep44446 |
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author | Ma, Ruiyu Deng, Linbei Xia, Yan Wei, Xianda Cao, Yingxi Guo, Ruolan Zhang, Rui Guo, Jing Liang, Desheng Wu, Lingqian |
author_facet | Ma, Ruiyu Deng, Linbei Xia, Yan Wei, Xianda Cao, Yingxi Guo, Ruolan Zhang, Rui Guo, Jing Liang, Desheng Wu, Lingqian |
author_sort | Ma, Ruiyu |
collection | PubMed |
description | Copy number variation (CNV) is of great significance in human evolution and disorders. Through tracing the parent-of-origin of de novo pathogenic CNVs, we are expected to investigate the relative contributions of germline genomic stability on reproductive health. In our study, short tandem repeat (STR) and single nucleotide polymorphism (SNP) were used to determine the parent-of-origin of 87 de novo pathogenic CNVs found in unrelated patients with intellectual disability (ID), developmental delay (DD) and multiple congenital anomalies (MCA). The results shown that there was a significant difference on the distribution of the parent-of-origin for different CNVs types (Chi-square test, p = 4.914 × 10(−3)). An apparently paternal bias existed in deletion CNVs and a maternal bias in duplication CNVs, indicating that the relative contribution of paternal germline variations is greater than that of maternal to the origin of deletions, and vice versa to the origin of duplications. By analyzing the sequences flanking the breakpoints, we also confirmed that non-allelic homologous recombination (NAHR) served as the major mechanism for the formation of recurrent CNVs whereas non-SDs-based mechanisms played a part in generating rare non-recurrent CNVs and might relate to the paternal germline bias in deletion CNVs. |
format | Online Article Text |
id | pubmed-5359547 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-53595472017-03-22 A clear bias in parental origin of de novo pathogenic CNVs related to intellectual disability, developmental delay and multiple congenital anomalies Ma, Ruiyu Deng, Linbei Xia, Yan Wei, Xianda Cao, Yingxi Guo, Ruolan Zhang, Rui Guo, Jing Liang, Desheng Wu, Lingqian Sci Rep Article Copy number variation (CNV) is of great significance in human evolution and disorders. Through tracing the parent-of-origin of de novo pathogenic CNVs, we are expected to investigate the relative contributions of germline genomic stability on reproductive health. In our study, short tandem repeat (STR) and single nucleotide polymorphism (SNP) were used to determine the parent-of-origin of 87 de novo pathogenic CNVs found in unrelated patients with intellectual disability (ID), developmental delay (DD) and multiple congenital anomalies (MCA). The results shown that there was a significant difference on the distribution of the parent-of-origin for different CNVs types (Chi-square test, p = 4.914 × 10(−3)). An apparently paternal bias existed in deletion CNVs and a maternal bias in duplication CNVs, indicating that the relative contribution of paternal germline variations is greater than that of maternal to the origin of deletions, and vice versa to the origin of duplications. By analyzing the sequences flanking the breakpoints, we also confirmed that non-allelic homologous recombination (NAHR) served as the major mechanism for the formation of recurrent CNVs whereas non-SDs-based mechanisms played a part in generating rare non-recurrent CNVs and might relate to the paternal germline bias in deletion CNVs. Nature Publishing Group 2017-03-21 /pmc/articles/PMC5359547/ /pubmed/28322228 http://dx.doi.org/10.1038/srep44446 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Ma, Ruiyu Deng, Linbei Xia, Yan Wei, Xianda Cao, Yingxi Guo, Ruolan Zhang, Rui Guo, Jing Liang, Desheng Wu, Lingqian A clear bias in parental origin of de novo pathogenic CNVs related to intellectual disability, developmental delay and multiple congenital anomalies |
title | A clear bias in parental origin of de novo pathogenic CNVs related to intellectual disability, developmental delay and multiple congenital anomalies |
title_full | A clear bias in parental origin of de novo pathogenic CNVs related to intellectual disability, developmental delay and multiple congenital anomalies |
title_fullStr | A clear bias in parental origin of de novo pathogenic CNVs related to intellectual disability, developmental delay and multiple congenital anomalies |
title_full_unstemmed | A clear bias in parental origin of de novo pathogenic CNVs related to intellectual disability, developmental delay and multiple congenital anomalies |
title_short | A clear bias in parental origin of de novo pathogenic CNVs related to intellectual disability, developmental delay and multiple congenital anomalies |
title_sort | clear bias in parental origin of de novo pathogenic cnvs related to intellectual disability, developmental delay and multiple congenital anomalies |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5359547/ https://www.ncbi.nlm.nih.gov/pubmed/28322228 http://dx.doi.org/10.1038/srep44446 |
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