Distribution and transmission of copy number variations of uncertain significance in 105 trios.

Abstract

BackgroundThe distribution and genetic characteristics of copy number variations (CNVs) remain unclear. Here, we investigated the distribution and transmission of CNVs of uncertain significance in fetuses.MethodsLow‐coverage massively parallels CNV sequencing of 105 families (parents and their fetuses) was performed to identify fetal CNVs of uncertain significance.ResultsIn the 105 fetuses, 176 CNVs of uncertain significance were detected, and the average number of CNVs carried by fetuses was 1.68 ± 0.80. Among the CNVs carried by the fetuses, 79.8% were inherited (~90.0% of the fetuses) and 20.2% were new mutations (~30.0% of the fetuses). We found that 58.9% CNVs were of maternal origin and 41.1% were of paternal origin. Among the CNV subtypes, de novo CNV distribution was significantly different from inherited CNV distribution. There was no difference in the distribution of maternal and paternal CNV subtypes in the fetuses. The proportion of microdeletions (36.7%) and microduplications (63.3%) was similar in the fetuses and parents. Furthermore, we found that when parents carried more CNVs of uncertain significance, the chance of passing them on to their offspring decreased.ConclusionThis study deepens our understanding of the genetic mechanisms associated with CNV transmission to assist clinicians in prenatal counseling.