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. 2017 Mar 21:7:44446.
doi: 10.1038/srep44446.

A clear bias in parental origin of de novo pathogenic CNVs related to intellectual disability, developmental delay and multiple congenital anomalies

Ruiyu Ma  1 , Linbei Deng  1 , Yan Xia  1 , Xianda Wei  1 , Yingxi Cao  1 , Ruolan Guo  1 , Rui Zhang  1 , Jing Guo  1 , Desheng Liang  1 , Lingqian Wu  1
Affiliations

A clear bias in parental origin of de novo pathogenic CNVs related to intellectual disability, developmental delay and multiple congenital anomalies

Ruiyu Ma et al. Sci Rep. .

Abstract

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.

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Conflict of interest statement

The authors declare no competing financial interests.

Figures

Figure 1
Figure 1. The distribution of 87 de novo CNVs on human chromosomes.
Red bars represent deletions and blue bars represent duplications.
Figure 2
Figure 2. A multiple comparison between paternal CNVs and maternal CNVs.
A clear difference was found when comparing the number of de novo CNVs according to CNV types. Paternal CNVs were noticeably more in deletions, and maternal were dominant in duplications especially in heterologous group.
Figure 3
Figure 3. The existence of flanking SDs nearby the CNV breakpoints.
See this image and copyright information in PMC

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