The genomic architecture of segmental duplications and associated copy number variants in dogs

Abstract

Structural variation is an important and abundant source of genetic and phenotypic variation. Here we describe the first systematic and genome-wide analysis of segmental duplications and associated copy number variants (CNVs) in the modern domesticated dog, Canis familiaris, which exhibits considerable morphological, physiological, and behavioral variation. Through computational analyses of the publicly available canine reference sequence, we estimate that segmental duplications comprise ;4.21% of the canine genome. Segmental duplications overlap 841 genes and are significantly enriched for specific biological functions such as immunity and defense and KRAB box transcription factors. We designed high-density tiling arrays spanning all predicted segmental duplications and performed aCGH in a panel of 17 breeds and a gray wolf. In total, we identified 3583 CNVs, ;68% of which were found in two or more samples that map to 678 unique regions. CNVs span 429 genes that are involved in a wide variety of biological processes such as olfaction, immunity, and gene regulation. Our results provide insight into mechanisms of canine genome evolution and generate a valuable resource for future evolutionary and phenotypic studies.

Genome-wide deserts for copy number variation in vertebrates

“…We Furthermore, we observed that CNVs in seven other vertebrate species reported by different research groups (chimpanzee 8 , macaque 7 , mouse 6 , rat 5 , dog 4 , cow 3 and chicken 2 ) were unlikely to overlap ORRs in those genomes (Supplementary Fig. S3a-g; chimpanzee: R ¼ À 0.10, Po2.2 Â 10 À 16 ; macaque: R ¼ À 0.07, P ¼ 4.1 Â 10 À 15 ; mouse: R ¼ À 0.25, Po2.2 Â 10 À 16 ; rat: R ¼ À 0.12, Po2.2 Â 10 À 16 ; dog: R ¼ À 0.14, Po2.2 Â 10 À 16 ; cow: R ¼ À 0.12, Po2.2 Â 10 À 16 and chicken: R ¼ À 0.067, P ¼ 1.8 Â 10 À 6 , product-moment correlation coefficient).…”

“…We identified 6,711 CNV genes (Supplementary Data 1). We obtained CNVs in seven vertebrate species from the literature (chimpanzee 8 , macaque 7 , mouse 6 , rat 5 , dog 4 , cow 3 and chicken 2 ). According to the genomic location of their CNVs, 1,006, 78, 445, 306, 329, 251 and 365 genes displayed CNVs for chimpanzee, macaque, mouse, rat, dog, cow and chicken, respectively.…”

“…Ongoing gene duplication or loss results in polymorphism at the population level, and these copy number variations (CNVs) have been observed in many organisms [2][3][4][5][6][7][8][9] . CNVs are frequently associated with human disease, and therefore it is important to understand the factors that influence the generation of CNVs in a genome [10][11][12][13][14][15] .…”

Gene copy-number polymorphism in nature

“…Indeed, copy-number variants (CNVs; sometimes also called 'copy-number polymorphisms' or CNPs) have been shown to be widespread in a variety of organisms, including humans (Sebat et al 2004;Conrad et al 2006;McCarroll et al 2006;Redon et al 2006), mice (Graubert et al 2007;She et al 2008), chimpanzees (Perry et al 2006, rhesus macaques (Lee et al 2008), cows (Liu et al 2010), dogs (Chen et al 2009;Nicholas et al 2009), chickens (Griffin et al 2008), maize (Springer et al 2009), Arabidopsis thaliana (Ossowski et al 2008), fruitflies (Dopman & Hartl 2007;Emerson et al 2008), Caenorhabditis elegans (Maydan et al 2010) and Saccharomyces cerevisiae (Carreto et al 2008). Though it is often harder to experimentally identify and genotype CNVs relative to SNPs and indels, many are big enough to encompass whole genes and are therefore more likely to affect organismal fitness.…”

Genome-wide Copy Number Variation in a Korean Native Chicken Breed

“…SNP는 전장 유전체에 걸친 대표적 유전적 다형성으로 널리 사용되고 있지만, 최근 또 다른 주요 유전적 변이로서 유전체의 구조적 변이(structural variation) 중 하나인 복제수변이(copy number variation, CNV) 가 유전적 다형성 및 진화 과정에 기여한다는 것이 밝혀졌 다 (Richard and David, 1998;Daniel et al, 1999). 이러한 CNV 는 개 (Nicholas et al, 2009), 소 (Hou et al, 2011), 젖소 (Stothard et al, 2011), 한우 Choi et al, 2014), 닭(Croojimans et al, 2013;Jia et al, 2013) (Skinner et al, 2009;Volker et al, 2010;Jia et al, 2012;Luo et al, 2013 …”