Copy number variants in the sheep genome detected using multiple approaches

Abstract

Background: Copy number variants (CNVs) are a type of polymorphism found to underlie phenotypic variation, both in humans and livestock. Most surveys of CNV in livestock have been conducted in the cattle genome, and often utilise only a single approach for the detection of copy number differences. Here we performed a study of CNV in sheep, using multiple methods to identify and characterise copy number changes. Comprehensive information from small pedigrees (trios) was collected using multiple platforms (array CGH, SNP chip and whole genome sequence data), with these data then analysed via multiple approaches to identify and verify CNVs. Results: In total, 3,488 autosomal CNV regions (CNVRs) were identified in this study, which substantially builds on an initial survey of the sheep genome that identified 135 CNVRs. The average length of the identified CNVRs was 19 kb (range of 1 kb to 3.6 Mb), with shorter CNVRs being more frequent than longer CNVRs. The total length of all CNVRs was 67.6Mbps, which equates to 2.7 % of the sheep autosomes. For individuals this value ranged from 0.24 to 0.55 %, and the majority of CNVRs were identified in single animals. Rather than being uniformly distributed throughout the genome, CNVRs tended to be clustered. Application of three independent approaches for CNVR detection facilitated a comparison of validation rates. CNVs identified on the Roche-NimbleGen 2.1M CGH array generally had low validation rates with lower density arrays, while whole genome sequence data had the highest validation rate (>60 %). Conclusions: This study represents the first comprehensive survey of the distribution, prevalence and characteristics of CNVR in sheep. Multiple approaches were used to detect CNV regions and it appears that the best method for verifying CNVR on a large scale involves using a combination of detection methodologies. The characteristics of the 3,488 autosomal CNV regions identified in this study are comparable to other CNV regions reported in the literature and provide a valuable and sizeable addition to the small subset of published sheep CNVs.

A global analysis of CNVs in Chinese indigenous fine-wool sheep populations using whole-genome resequencing

“…The CNVRs identi ed in these previous studies were different to some extent, which may have been related to the differences in sheep breeds, sample sizes, CNV detection platforms and CNV calling algorithms used. However, it is noteworthy that the CNVRs identi ed in this study had high overlapping ratios (27.93%-55.46%) with the CNVRs identi ed by Liu et al, Ma et al, Zhu et al, and Ma et al, but had low overlapping ratios (4.39%-12.59%) with the CNVRs detected by Fontanesi et al, and Jenkins et al, [7,11,13,15,16,28]. The four studies with which there were high overlapping ratios all used Chinese indigenous sheep breeds or Chinese cultivated sheep breeds as the study subjects, whereas the two studies with which there were low overlapping ratios used foreign sheep breeds.…”

Genome-wide Analysis of CNVs in Three Populations of Tibetan Sheep using Whole-genome Resequencing

“…Due to the difference in CNV detection platforms, the quantity of detected CNVs varies widely in different studies. In terms of the CNVs captured by aCGH and SNP chips, the number usually ranges from dozens to hundreds, and the average length is approximately 100-300 kb [28][29][30][31][32]. Using whole genome resequencing, Cheng et al [33] reported that 4301 CNVRs were identi ed in three Chinese breeds.…”

Copy Number Variation in Domestication

“…In the case of rice, a recent study of 3010 rice varieties identified thousands of deletions and hundreds of duplications affecting between 100 bp and 1 Mb [47]. Indeed, there are often significant inconsistencies in the results of CNV analyses from different studies within the same species due to differences in sample sizes, breeds used, and methodologies of CNV detection (Box 1) [22,48,49]. This was highlighted in a recent analysis, albeit in a domesticated animal species, which characterized CNVs in European cattle (Bos taurus) populations and compared the results to 18 previous studies [39].…”