Genome-wide patterns of copy number variation in the diversified chicken genomes using next-generation sequencing

Copy number variation (CNV) is important and widespread in the genome, and is a major cause of disease and phenotypic diversity. Herein, we perform genome-wide CNV analysis in 12 diversified chicken genomes based on whole genome sequencing. A total of 9,025 CNV regions (CNVRs) covering 100.1 Mb and representing 9.6% of the chicken genome are identified, ranging in size from 1.1 to 268.8 kb with an average of 11.1 kb. Sequencing-based predictions are confirmed at high validation rate by two independent approaches, including array comparative genomic hybridization (aCGH) and quantitative PCR (qPCR). The Pearson?s correlation values between sequencing and aCGH results range from 0.395 to 0.740, and qPCR experiments reveal a positive validation rate of 91.71% and a false negative rate of 22.43%. In total, 2,188 predicted CNVRs (24.2%) span 2,182 RefSeq genes (36.8%) associated with specific biological functions. Besides two previously accepted copy number variable genesEDN3andPRLR, we also find some promising genes with potential in phenotypic variants.FZD6andLIMS1, two genes related to diseases susceptibility and resistance are covered by CNVRs. Highly duplicatedSOCS2may lead to higher bone mineral density. Entire or partial duplication of some genes likePOPDC3andLBFABPmay have great economic importance in poultry breeding. Our results based on extensive genetic diversity provide the first individualized chicken CNV map and genome-wide gene copy number estimates and warrant future CNV association studies for important traits of chickens.

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A genome-wide survey of copy number variation regions in various chicken breeds by array comparative genomic hybridization method

Animal Genetics ◽

10.1111/j.1365-2052.2011.02308.x ◽

2012 ◽

Vol 43 (3) ◽

pp. 282-289 ◽

Cited By ~ 26

Author(s):

Y. Wang ◽

X. Gu ◽

C. Feng ◽

C. Song ◽

X. Hu ◽

...

Keyword(s):

Copy Number Variation ◽

Copy Number ◽

Array Comparative Genomic Hybridization ◽

Comparative Genomic ◽

Hybridization Method ◽

Genome Wide ◽

A Genome ◽

Number Variation ◽

Chicken Breeds ◽

Genome Wide Survey

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Genome-Wide Association Studies of Copy Number Variation in Autism Spectrum Disorder

Autism - A Neurodevelopmental Journey from Genes to Behaviour ◽

10.5772/22207 ◽

2011 ◽

Author(s):

Hae-Jin Hu ◽

Yeun-Jun Chung

Keyword(s):

Autism Spectrum Disorder ◽

Copy Number Variation ◽

Copy Number ◽

Association Studies ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Genome Wide ◽

Number Variation

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Genome-wide detection of CNV regions and their potential association with growth and fatness traits in Duroc pigs

BMC Genomics ◽

10.1186/s12864-021-07654-7 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Yibin Qiu ◽

Rongrong Ding ◽

Zhanwei Zhuang ◽

Jie Wu ◽

Ming Yang ◽

...

Keyword(s):

Copy Number Variation ◽

Complex Traits ◽

Copy Number ◽

Association Studies ◽

Average Daily Gain ◽

Genome Wide Association Studies ◽

Potential Candidate ◽

Genome Wide ◽

Number Variation ◽

Genetic Mechanisms

Abstract Background In the process of pig breeding, the average daily gain (ADG), days to 100 kg (AGE), and backfat thickness (BFT) are directly related to growth rate and fatness. However, the genetic mechanisms involved are not well understood. Copy number variation (CNV), an important source of genetic diversity, can affect a variety of complex traits and diseases and has gradually been thrust into the limelight. In this study, we reported the genome-wide CNVs of Duroc pigs using SNP genotyping data from 6627 animals. We also performed a copy number variation region (CNVR)-based genome-wide association studies (GWAS) for growth and fatness traits in two Duroc populations. Results Our study identified 953 nonredundant CNVRs in U.S. and Canadian Duroc pigs, covering 246.89 Mb (~ 10.90%) of the pig autosomal genome. Of these, 802 CNVRs were in U.S. Duroc pigs with 499 CNVRs were in Canadian Duroc pigs, indicating 348 CNVRs were shared by the two populations. Experimentally, 77.8% of nine randomly selected CNVRs were validated through quantitative PCR (qPCR). We also identified 35 CNVRs with significant association with growth and fatness traits using CNVR-based GWAS. Ten of these CNVRs were associated with both ADG and AGE traits in U.S. Duroc pigs. Notably, four CNVRs showed significant associations with ADG, AGE, and BFT, indicating that these CNVRs may play a pleiotropic role in regulating pig growth and fat deposition. In Canadian Duroc pigs, nine CNVRs were significantly associated with both ADG and AGE traits. Further bioinformatic analysis identified a subset of potential candidate genes, including PDGFA, GPER1, PNPLA2 and BSCL2. Conclusions The present study provides a necessary supplement to the CNV map of the Duroc genome through large-scale population genotyping. In addition, the CNVR-based GWAS results provide a meaningful way to elucidate the genetic mechanisms underlying complex traits. The identified CNVRs can be used as molecular markers for genetic improvement in the molecular-guided breeding of modern commercial pigs.

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Current analysis platforms and methods for detecting copy number variation

Physiological Genomics ◽

10.1152/physiolgenomics.00082.2012 ◽

2013 ◽

Vol 45 (1) ◽

pp. 1-16 ◽

Cited By ~ 45

Author(s):

Wenli Li ◽

Michael Olivier

Keyword(s):

Copy Number Variation ◽

Copy Number ◽

Association Studies ◽

Genome Wide Association Studies ◽

Genomic Structural Variation ◽

Disease Phenotypes ◽

Human Genomes ◽

Genome Wide ◽

Number Variation ◽

Genomic Regions

Copy number variation (CNV), generated through duplication or deletion events that affect one or more loci, is widespread in the human genomes and is often associated with functional consequences that may include changes in gene expression levels or fusion of genes. Genome-wide association studies indicate that some disease phenotypes and physiological pathways might be impacted by CNV in a small number of characterized genomic regions. However, the pervasiveness and full impact of such variation remains unclear. Suitable analytic methods are needed to thoroughly mine human genomes for genomic structural variation, and to explore the interplay between observed CNV and disease phenotypes, but many medical researchers are unfamiliar with the features and nuances of recently developed technologies for detecting CNV. In this article, we evaluate a suite of commonly used and recently developed approaches to uncovering genome-wide CNVs and discuss the relative merits of each.

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Genotyping Allelic and Copy Number Variation in the Immunoglobulin Heavy Chain Locus

10.1101/042226 ◽

2016 ◽

Cited By ~ 1

Author(s):

Shishi Luo ◽

Jane A Yu ◽

Yun S. Song

Keyword(s):

Copy Number Variation ◽

Copy Number ◽

Allelic Variation ◽

Association Studies ◽

Adaptive Immune Response ◽

Gene Copy Number ◽

Population Level ◽

European Ancestry ◽

Gene Copy ◽

Number Variation

The study of genomic regions that contain gene copies and structural variation is a major challenge in modern genomics. Unlike variation involving single nucleotide changes, data on the variation of copy number is difficult to collect and few tools exist for analyzing the variation between individuals. The immunoglobulin heavy variable (IGHV) locus, which plays an integral role in the adaptive immune response, is an example of a genomic region that is known to vary in gene copy number. Lack of standard methods to genotype this region prevents it from being included in association studies and is holding back the growing field of antibody repertoire analysis. Here, we establish a convention of representing the locus in terms of a reference panel of operationally distinguishable segments defined by hierarchical clustering. Using this reference set, we develop a pipeline that identifies copy number and allelic variation in the IGHV locus from whole-genome sequencing reads. Tests on simulated reads demonstrate that our approach is feasible and accurate for detecting the presence and absence of gene segments using reads as short as 70 bp. With reads 100 bp and longer, coverage depth can also be used to determine copy number. When applied to a family of European ancestry, our method finds new copy number variants and confirms existing variants. This study paves the way for analyzing population-level patterns of variation in the IGHV locus in larger diverse datasets and for quantitatively handling regions of copy number variation in other structurally varying and complex loci.

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Copy Number Variation Accuracy in Genome-Wide Association Studies

Human Heredity ◽

10.1159/000324683 ◽

2011 ◽

Vol 71 (3) ◽

pp. 141-147 ◽

Cited By ~ 10

Author(s):

Peng Lin ◽

Sarah M. Hartz ◽

Jen-Chyong Wang ◽

Robert F. Krueger ◽

Tatiana M. Foroud ◽

...

Keyword(s):

Copy Number Variation ◽

Copy Number ◽

Association Studies ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Genome Wide ◽

Number Variation

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Genome wide association studies (GWAS) and copy number variation (CNV) studies of the major psychoses: What have we learnt?

Neuroscience & Biobehavioral Reviews ◽

10.1016/j.neubiorev.2011.09.001 ◽

2012 ◽

Vol 36 (1) ◽

pp. 556-571 ◽

Cited By ~ 71

Author(s):

Kok Wei Lee ◽

Puay San Woon ◽

Yik Ying Teo ◽

Kang Sim

Keyword(s):

Copy Number Variation ◽

Copy Number ◽

Association Studies ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Genome Wide ◽

Number Variation

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The population genetics of adaptation through copy-number variation in a fungal plant pathogen

10.1101/2021.12.10.472168 ◽

2021 ◽

Author(s):

Luzia Stalder ◽

Ursula Oggenfuss ◽

Norfarhan Mohd-Assaad ◽

Daniel Croll

Keyword(s):

Copy Number Variation ◽

Fungal Pathogen ◽

Copy Number ◽

Copy Number Variations ◽

Temperature Adaptation ◽

Gene Copy ◽

Gene Duplications ◽

Genome Wide ◽

A Genome ◽

Number Variation

ABSTRACTMicrobial pathogens can rapidly adapt to changing environments such as the application of pesticides or host resistance. Copy number variations (CNV) are a major source of adaptive genetic variation for recent adaptation. Here, we analyze how a major fungal pathogen of barley, Rhynchosporium commune, has adapted to host environment, fungicide and temperature challenges. We screen the genomes of 126 isolates sampled across a worldwide set of populations and identify a total of 7’879 gene duplications and 116 gene deletions. Most gene duplications result from segmental chromosomal duplications. We find that genes showing recent gains or losses are enriched in functions related to host exploitation (i.e. effectors and cell wall degrading enzymes). We perform a phylogeny-informed genome-wide association study (GWAS) and identify 191 copy-number variants associated with different pathogenesis and temperature related traits, including a large segmental duplication of CYP51A that has contributed to the emergence of azole resistance. Additionally, we use a genome-wide SNP dataset to replicate the GWAS and contrast it with the CNV-focused analysis. We find that frequencies of adaptive CNV alleles show high variation among populations for traits under strong selection such as fungicide resistance. In contrast, adaptive CNV alleles underpinning temperature adaptation tend to be near fixation. Finally, we show that transposable elements are important drivers of recent gene copy-number variation. Loci showing signatures of recent positive selection are enriched in miniature inverted repeat transposons. Our findings show how extensive segmental duplications create the raw material for recent adaptation in global populations of a fungal pathogen.

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