Trios-based inquiry into de novo copy number variants in the swine genome

Magdalena Frąszczak; Błażej Nowak; Martyna Kaźmierczak; Magda Mielczarek

doi:10.2478/aoas-2025-0120

Abstract

Copy number variation (CNV) plays an important role in determining multiple phenotypic traits due to these large genomic segments having the potential to disrupt functionally important genomic regions. The current study investigated the prevalence, distribution, and functional impacts of de novo CNVs in swine genomes and compared them with those that were inherited. CNV patterns showed high similarity within nuclear families, indicating that most CNVs are inherited, yet 9% arose de novo and contributed to individual variation. The underlying systematic pattern indicated that de novo deletions are shorter than inherited ones, which has essential meaning, especially for functionally important genomic locations. Moreover, de novo deletions were not uniformly distributed along the genome, forming clusters. Despite the potentially more severe impact of deletions, more de novo deletions than duplications were present in offspring genomes. The highest CNV-QTL (quantitative trait loci) overlap was found for teat number, reflecting strong selection for this trait. Overlaps also occurred in key reproductive and production traits. Multiple CNVs in the same gene may suggest regions prone to structural variation, as seen in testis-expressed 14 (TEX14), linked to pig infertility, and as parkin RBR E3 ubiquitin protein ligase (PRKN), a known CNV hotspot in humans. Deletions were primarily located in introns, with no significant enrichment of the Gene Ontology (GO) terms or Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. De novo duplications mainly affected genes related to environmental interactions, such as the immune response and olfactory receptors.

References

1000 Genomes Project, Mills R.E., Walter K., Stewart C., Handsaker R.E., Chen K., Alkan C., Abyzov A., Yoon S.C., Ye K., Cheetham R.K., Chinwalla A., Conrad D.F., Fu Y., Grubert F., Hajirasouliha I., Hormozdiari F., Iakoucheva L.M., Iqbal Z., Kang S., Kidd J.M., Konkel M.K., Korn J., Khurana E., Kural D., Lam H.Y.K., Leng J., Li R., Li Y., Lin C.-Y., Luo R., Mu X.J., Nemesh J., Peckham H.E., Rausch T., Scally A., Shi X., Stromberg M.P., Stütz A.M., Urban A.E., Walker J.A., Wu J., Zhang Y., Zhang Z.D., Batzer M.A., Ding L., Marth G.T., McVean G., Sebat J., Snyder M., Wang J., Ye K., Eichler E.E., Gerstein M.B., Hurles M.E., Lee C., McCarroll S.A., Korbel J.O. (2011). Mapping copy number variation by population-scale genome sequencing. Nature, 470: 59–65.
Search in Google Scholar Back to article
Abyzov A., Urban A.E., Snyder M., Gerstein M. (2011). CNVnator: An approach to discover, genotype, and characterize typical and atypical CNVs from family and population genome sequencing. Genome Res., 21: 974–984.
Search in Google Scholar Back to article
Acuna-Hidalgo R., Veltman J.A., Hoischen A. (2016). New insights into the generation and role of de novo mutations in health and disease. Genome Biol., 17: 241.
Search in Google Scholar Back to article
Andrews S. (2010). FastQC: A Quality Control Tool for High Throughput Sequence Data.
Search in Google Scholar Back to article
Arias K.D., Pablo Gutiérrez J., Fernandez I., Menéndez-Arias N.A., Álvarez I., Goyache F. (2023). Segregation patterns and inheritance rate of copy number variations regions assessed in a Gochu Asturcelta pig pedigree. Gene, 854: 147111.
Search in Google Scholar Back to article
Arlt M.F., Wilson T.E., Glover T.W. (2012). Replication stress and mechanisms of CNV formation. Curr. Opin. Genet. Dev., 22: 204–210.
Search in Google Scholar Back to article
Ashburner M., Ball C.A., Blake J.A., Botstein D., Butler H., Cherry J.M., Davis A.P., Dolinski K., Dwight S.S., Eppig J.T., Harris M.A., Hill D.P., Issel-Tarver L., Kasarskis A., Lewis S., Matese J.C., Richardson J.E., Ringwald M., Rubin G.M., Sherlock G. (2000). Gene Ontology: tool for the unification of biology. Nat. Genet., 25: 25–29.
Search in Google Scholar Back to article
Bickhart D.M., Liu G.E. (2014). The challenges and importance of structural variation detection in livestock. Front. Genet., 5: 37.
Search in Google Scholar Back to article
Bolger A.M., Lohse M., Usadel B. (2014). Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics, 30: 2114–2120.
Search in Google Scholar Back to article
Boonin P., Klumsathian S., Iemwimangsa N., Sensorn I., Charoenyingwatana A., Chantratita W., Chareonsirisuthigul T. (2025). Detection of Genetic Variants in Thai Population by Trio-Based Whole-Genome Sequencing Study. Biology, 14: 301.
Search in Google Scholar Back to article
Borchers N., Reinsch N., Kalm E. (2004). The number of ribs and vertebrae in a Piétrain cross: variation, heritability and effects on performance traits. J. Anim. Breed. Genet., 121: 392–403.
Search in Google Scholar Back to article
Chan K., Gordenin D.A. (2015). Clusters of Multiple Mutations: Incidence and Molecular Mechanisms. Annu. Rev. Genet., 49: 243–267.
Search in Google Scholar Back to article
Chen R., Irwin D.M., Zhang Y.-P. (2012). Differences in Selection Drive Olfactory Receptor Genes in Different Directions in Dogs and Wolf. Mol. Biol. Evol., 29: 3475–3484.
Search in Google Scholar Back to article
Dallal G.E., Wilkinson L. (1986). An Analytic Approximation to the Distribution of Lilliefors's Test Statistic for Normality. Am. Stat., 40: 294–296.
Search in Google Scholar Back to article
Du H., Jolly A., Grochowski C.M., Yuan B., Dawood M., Jhangiani S.N., Li H., Muzny D., Fatih J.M., Coban-Akdemir Z., Carlin M.E., Scheuerle A.E., Witzl K., Posey J.E., Pendleton M., Harrington E., Juul S., Hastings P.J., Bi W., Gibbs R.A., Sedlazeck F.J., Lupski J. R., Carvalho C.M.B., Liu P. (2022). The multiple de novo copy number variant (MdnCNV) phenomenon presents with peri-zygotic DNA mutational signatures and multilocus pathogenic variation. Genome Med., 14: 122.
Search in Google Scholar Back to article
Esteve-Codina A., Paudel Y., Ferretti L., Raineri E., Megens H.-J., Silió L., Rodríguez M.C., Groenen M.A., Ramos-Onsins S.E., Pérez-Enciso M. (2013). Dissecting structural and nucleotide genome-wide variation in inbred Iberian pigs. BMC Genomics, 14: 148.
Search in Google Scholar Back to article
Ewels P., Magnusson M., Lundin S., Käller M. (2016). MultiQC: summarize analysis results for multiple tools and samples in a single report. Bioinformatics, 32: 3047–3048.
Search in Google Scholar Back to article
Fadista J., Nygaard M., Holm L.-E., Thomsen B., Bendixen C. (2008). A Snapshot of CNVs in the Pig Genome. PLoS ONE, 3: e3916.
Search in Google Scholar Back to article
Feuk L., Carson A.R., Scherer S.W. (2006). Structural variation in the human genome. Nat. Rev. Genet., 7: 85–97.
Search in Google Scholar Back to article
Gao N., Chen Y., Liu X., Zhao Y., Zhu L., Liu A., Jiang W., Peng X., Zhang C., Tang Z., Li X. Chen Y. (2019). Weighted single-step GWAS identified candidate genes associated with semen traits in a Duroc boar population. BMC Genomics, 20: 797.
Search in Google Scholar Back to article
Ge S.X., Jung D., Yao R. (2020). ShinyGO: a graphical gene-set enrichment tool for animals and plants. Bioinforma. Oxf. Engl., 36: 2628–2629.
Search in Google Scholar Back to article
Geistlinger L., Da Silva V.H., Cesar A.S.M., Tizioto P.C., Waldron L., Zimmer R., Regitano L.C.D.A., Coutinho L.L. (2018). Widespread modulation of gene expression by copy number variation in skeletal muscle. Sci. Rep., 8: 1399.
Search in Google Scholar Back to article
Gilissen C., Hehir-Kwa J.Y., Thung D.T., Van De Vorst M., Van Bon B.W.M., Willemsen M.H., Kwint M., Janssen I.M., Hoischen A., Schenck A., Leach R., Klein R., Tearle R., Bo T., Pfundt R., Yntema H.G., De Vries B.B.A., Kleefstra T., Brunner H.G., Vissers L.E.L.M., Veltman J.A. (2014). Genome sequencing identifies major causes of severe intellectual disability. Nature, 511: 344–347.
Search in Google Scholar Back to article
Giuffra E., Törnsten A., Marklund S., Bongcam-Rudloff E., Chardon P., Kijas J.M.H., Anderson S.I., Archibald A.L., Andersson L. (2002). A large duplication associated with dominant white color in pigs originated by homologous recombination between LINE elements flanking KIT. Mamm. Genome, 13: 569–577.
Search in Google Scholar Back to article
Groenen M.A.M., Archibald A.L., Uenishi H., Tuggle C.K., Takeuchi Y., Rothschild M.F., Rogel-Gaillard C., Park C., Milan D., Megens H.-J., Li S., Larkin D.M., Kim H., Frantz L.A.F., Caccamo M., Ahn H., Aken B.L., Anselmo A., Anthon C., Auvil L., Badaoui B., Beattie C.W., Bendixen C., Berman D., Blecha F., Blomberg J., Bolund L., Bosse M., Botti S., Bujie Z., Bystrom M., Capitanu B., Carvalho-Silva D., Chardon P., Chen C., Cheng R., Choi S.-H., Chow W., Clark R.C., Clee C., Crooijmans R.P.M.A., Dawson H.D., Dehais P., De Sapio F., Dibbits B., Drou N., Du Z.-Q., Eversole K., Fadista J., Fairley S., Faraut T., Faulkner G.J., Fowler K.E., Fredholm M., Fritz E., Gilbert J.G.R., Giuffra E., Gorodkin J., Griffin D.K., Harrow J.L., Hayward A., Howe K., Hu Z.-L., Humphray S.J., Hunt T., Hornshøj H., Jeon J.-T., Jern P., Jones M., Jurka J., Kanamori H., Kapetanovic R., Kim J., Kim J.-H., Kim K.-W., Kim T.-H., Larson G., Lee K., Lee K.-T., Leggett R., Lewin H.A., Li Y., Liu W., Loveland J.E., Lu Y., Lunney J.K., Ma J., Madsen O., Mann K., Matthews L., McLaren S., Morozumi T., Murtaugh M.P., Narayan J., Truong Nguyen D., Ni P., Oh S.-J., Onteru S., Panitz F., Park E.-W., Park H.-S., Pascal G., Paudel Y., Perez-Enciso M., Ramirez-Gonzalez R., Reecy J.M., Rodriguez-Zas S., Rohrer G.A., Rund L., Sang Y., Schachtschneider K., Schraiber J.G., Schwartz J., Scobie L., Scott C., Searle S., Servin B., Southey B.R., Sperber G., Stadler P., Sweedler J.V., Tafer H., Thomsen B., Wali R., Wang J., Wang J., White S., Xu X., Yerle M., Zhang G., Zhang J., Zhang J., Zhao S., Rogers J., Churcher C., Schook L.B. (2012). Analyses of pig genomes provide insight into porcine demography and evolution. Nature, 491: 393–398.
Search in Google Scholar Back to article
Hamanaka K., Miyake N., Mizuguchi T., Miyatake S., Uchiyama Y., Tsuchida N., Sekiguchi F., Mitsuhashi S., Tsurusaki Y., Nakashima M., Saitsu H., Yamada K., Sakamoto M., Fukuda H., Ohori S., Saida K., Itai T., Azuma Y., Koshimizu E., Fujita A., Erturk B., Hiraki Y., Ch'ng G.-S., Kato M., Okamoto N., Takata A., Matsumoto N. (2022). Large-scale discovery of novel neurodevelopmental disorder-related genes through a unified analysis of single-nucleotide and copy number variants. Genome Med., 14: 40.
Search in Google Scholar Back to article
Hehir-Kwa J.Y., Rodriguez-Santiago B., Vissers L.E., De Leeuw N., Pfundt R., Buitelaar J.K., Perez-Jurado L.A., Veltman J.A. (2011). De novo copy number variants associated with intellectual disability have a paternal origin and age bias. J. Med. Genet., 48: 776–778.
Search in Google Scholar Back to article
Henrichsen C.N., Vinckenbosch N., Zöllner S., Chaignat E., Pradervand S., Schütz F., Ruedi M., Kaessmann H., Reymond A. (2009). Segmental copy number variation shapes tissue transcriptomes. Nat. Genet., 41: 424–429.
Search in Google Scholar Back to article
Höps W., Rausch T., Jendrusch M., Human Genome Structural Variation Consortium (HGSVC), Ashraf H., Audano P.A., Austine O., Basile A.O., Beck C.R., Jan Bonder M., Byrska-Bishop M., Chaisson M.J.P., Chong Z., Corvelo A., Devine S.E., Ebert P., Ebler J., Eichler E.E., Gerstein M.B., Hallast P., Harvey W.T., Hasenfeld P., Hastie A.R., Henglin M., Hoekzema K., Hsieh P., Hunt S., Konkel M.K., Kordosky J., Lansdorp P.M., Lee C., Lee W.-P., Lewis A.P., Li C., Lin J., Loftus M., Logsdon G.A., Marschall T., Mills R.E., Mostovoy Y., Munson K.M., Narzisi G., Pang A., Porubsky D., Prodanov T., Rodriguez-Martin B., Shi X., Surapaneni L., Talkowski M.E., Yilmaz F., Yoo D., Zhou W., Zody M.C., Korbel J.O., Sedlazeck F.J. (2024). Impact and characterization of serial structural variations across humans and great apes. Nat. Commun., 15: 8007.
Search in Google Scholar Back to article
Hu Z.-L., Park C.A., Reecy J.M. (2022). Bringing the Animal QTLdb and CorrDB into the future: meeting new challenges and providing updated services. Nucleic Acids Res., 50: 956–961.
Search in Google Scholar Back to article
Jang J., Kim B., Jhang S.Y., Ahn B., Kang M., Park C., Cho E.S., Kim Y.-S., Park W., Kim H. (2023). Population differentiated copy number variation between Eurasian wild boar and domesticated pig populations. Sci. Rep., 13: 1115.
Search in Google Scholar Back to article
Jiang J., Wang J., Wang H., Zhang Y., Kang H., Feng X., Wang J., Yin Z., Bao W., Zhang Q., Liu J.-F. (2014). Global copy number analyses by next generation sequencing provide insight into pig genome variation. BMC Genomics, 15: 593.
Search in Google Scholar Back to article
Kanehisa M., Furumichi M., Tanabe M., Sato Y., Morishima K. (2017). KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res., 45: D353–D361.
Search in Google Scholar Back to article
Keel B.N., Nonneman D.J., Lindholm-Perry A.K., Oliver W.T., Rohrer G.A. (2019). A Survey of Copy Number Variation in the Porcine Genome Detected From Whole-Genome Sequence. Front. Genet., 10: 737.
Search in Google Scholar Back to article
Kirov G., Pocklington A.J., Holmans P., Ivanov D., Ikeda M., Ruderfer D., Moran J., Chambert K., Toncheva D., Georgieva L., Grozeva D., Fjodorova M., Wollerton R., Rees E., Nikolov I., Van De Lagemaat L.N., Bayés À., Fernandez E., Olason P.I., Böttcher Y., Komiyama N.H., Collins M.O., Choudhary J., Stefansson K., Stefansson H., Grant S.G.N., Purcell S., Sklar P., O'Donovan M.C., Owen M.J. (2012). De novo CNV analysis implicates specific abnormalities of postsynaptic signalling complexes in the pathogenesis of schizophrenia. Mol. Psychiatry, 17: 142–153.
Search in Google Scholar Back to article
Krepischi A.C., Achatz M.I.W., Santos E.M., Costa S.S., Lisboa B.C., Brentani H., Santos T.M., Gonçalves A., Nóbrega A.F., Pearson P.L., Vianna-Morgante A.M., Carraro D.M., Brentani R.R., Rosenberg C. (2012). Germline DNA copy number variation in familial and early-onset breast cancer. Breast Cancer Res., 14: R24.
Search in Google Scholar Back to article
Li H., Durbin R. (2009). Fast and accurate short read alignment with Burrows–Wheeler transform. Bioinformatics, 25: 1754–1760.
Search in Google Scholar Back to article
Li H., Handsaker B., Wysoker A., Fennell T., Ruan J., Homer N., Marth G., Abecasis G., Durbin R., 1000 Genome Project Data Processing Subgroup. (2009). The Sequence Alignment/Map format and SAMtools. Bioinforma. Oxf. Engl., 25: 2078–2079.
Search in Google Scholar Back to article
Li Y., Mei S., Zhang X., Peng X., Liu G., Tao H., Wu H., Jiang S., Xiong Y., Li F. (2012). Identification of genome-wide copy number variations among diverse pig breeds by array CGH. BMC Genomics, 13: 725.
Search in Google Scholar Back to article
Lin, Y.-L., Gokcumen O. (2019). Fine-Scale Characterization of Genomic Structural Variation in the Human Genome Reveals Adaptive and Biomedically Relevant Hotspots. Genome Biol. Evol., 11: 1136–1151.
Search in Google Scholar Back to article
Liu G.E., Bickhart D.M. (2012). Copy number variation in the cattle genome. Funct. Integr. Genomics, 12: 609–624.
Search in Google Scholar Back to article
Liu Y., Yang X., Jing X., He X., Wang L., Liu Y., Liu D. (2017). Transcriptomics Analysis on Excellent Meat Quality Traits of Skeletal Muscles of the Chinese Indigenous Min Pig Compared with the Large White Breed. Int. J. Mol. Sci., 19: 21.
Search in Google Scholar Back to article
Long Y., Su Y., Ai H., Zhang Z., Yang B., Ruan G., Xiao S., Liao X., Ren J., Huang L., Ding N. (2016). A genome-wide association study of copy number variations with umbilical hernia in swine. Anim. Genet., 47: 298–305.
Search in Google Scholar Back to article
McCarroll S.A., Kuruvilla F.G., Korn J.M., Cawley S., Nemesh J., Wysoker A., Shapero M.H., de Bakker P.I.W., Maller J.B., Kirby A., Elliott A.L., Parkin M., Hubbell E., Webster T., Mei R., Veitch J., Collins P.J., Handsaker R., Lincoln S., Nizzari M., Blume J., Jones K.W., Rava R., Daly M.J., Gabriel S.B., Altshuler D. (2008). Integrated detection and population-genetic analysis of SNPs and copy number variation. Nat. Genet., 40: 1166–1174.
Search in Google Scholar Back to article
McLaren W., Gil L., Hunt S.E., Riat H.S., Ritchie G.R.S., Thormann A., Flicek P., Cunningham F. (2016). The Ensembl Variant Effect Predictor. Genome Biol., 17: 122.
Search in Google Scholar Back to article
Mielczarek M., Frąszczak M., Zielak-Steciwko A.E., Nowak B., Hofman B., Pierścińska J., Kruszyński W., Szyda J. (2023). An effect of large-scale deletions and duplications on transcript expression. Funct. Integr. Genomics, 23: 19.
Search in Google Scholar Back to article
Moreno-Estrada A., Casals F., Ramirez-Soriano A., Oliva B., Calafell F., Bertranpetit J., Bosch E. (2007). Signatures of Selection in the Human Olfactory Receptor OR5I1 Gene. Mol. Biol. Evol., 25: 144–154.
Search in Google Scholar Back to article
van Ommen G.-J.B. (2005). Frequency of new copy number variation in humans. Nat. Genet., 37: 333–334.
Search in Google Scholar Back to article
Pabst R. (2020). The pig as a model for immunology research. Cell Tissue Res., 380: 287–304.
Search in Google Scholar Back to article
Paudel Y., Madsen O., Megens H.-J., Frantz L.A., Bosse M., Bastiaansen J.W., Crooijmans R.P., Groenen M.A. (2013). Evolutionary dynamics of copy number variation in pig genomes in the context of adaptation and domestication. BMC Genomics, 14: 449.
Search in Google Scholar Back to article
Paudel Y., Madsen O., Megens H.-J., Frantz L.A.F., Bosse M., Crooijmans R.P.M.A., Groenen M.A.M. (2015). Copy number variation in the speciation of pigs: a possible prominent role for olfactory receptors. BMC Genomics, 16: 330.
Search in Google Scholar Back to article
Pereira S.S.S., Pinto I.P., Santos V.C.D.P., Silva R.C., Costa E.O.A., Cruz A.S.D., Cruz A.D.D., Silva C.C.D., Minasi L.B. (2024). Analysis of parental origin of de novo pathogenic CNVs in patients with intellectual disability. Genet. Mol. Biol., 47: e20230313.
Search in Google Scholar Back to article
Pös O., Radvanszky J., Buglyó G., Pös Z., Rusnakova D., Nagy B., Szemes T. (2021). DNA copy number variation: Main characteristics, evolutionary significance, and pathological aspects. Biomed. J., 44: 548–559.
Search in Google Scholar Back to article
Qian R., Xie F., Zhang W., Kong J., Zhou X., Wang C., Li X. (2023). Genome-wide detection of CNV regions between Anqing six-end-white and Duroc pigs. Mol. Cytogenet., 16: 12.
Search in Google Scholar Back to article
R Core Team (2022). R: A language and environment for statistical computing.
Search in Google Scholar Back to article
Ramayo-Caldas Y., Crespo-Piazuelo D., Morata J., González-Rodríguez O., Sebastià C., Castello A., Dalmau A., Ramos-Onsins S., Alexiou K.G., Folch J.M., Quintanilla R., Ballester M. (2023). Copy Number Variation on ABCC2-DNMBP Loci Affects the Diversity and Composition of the Fecal Microbiota in Pigs. Microbiol. Spectr., 11: e05271-22.
Search in Google Scholar Back to article
Revay T., Quach A.T., Maignel L., Sullivan B., King W.A. (2015). Copy number variations in high and low fertility breeding boars. BMC Genomics, 16: 280.
Search in Google Scholar Back to article
Revilla M., Puig-Oliveras A., Castelló A., Crespo-Piazuelo D., Paludo E., Fernández A.I., Ballester M., Folch J.M. (2017). A global analysis of CNVs in swine using whole genome sequence data and association analysis with fatty acid composition and growth traits. PLOS ONE, 12: e0177014.
Search in Google Scholar Back to article
Rohrer G.A., Nonneman D.J. (2017). Genetic analysis of teat number in pigs reveals some developmental pathways independent of vertebra number and several loci which only affect a specific side. Genet. Sel. Evol., 49: 4.
Search in Google Scholar Back to article
Sanders S.J., He X., Willsey A.J., Ercan-Sencicek A.G., Samocha K.E., Cicek A.E., Murtha M.T., Bal V.H., Bishop S.L., Dong S., Goldberg A.P., Jinlu C., Keaney J.F., Klei L., Mandell J.D., Moreno-De-Luca D., Poultney C.S., Robinson E.B., Smith L., Solli-Nowlan T., Su M.Y., Teran N.A., Walker M.F., Werling D.M., Beaudet A.L., Cantor R.M., Fombonne E., Geschwind D.H., Grice D.E., Lord C., Lowe J.K., Mane S.M., Martin D.M., Morrow E.M., Talkowski M.E., Sutcliffe J.S., Walsh C.A., Yu T.W., Ledbetter D.H., Martin C.L., Cook E.H., Buxbaum J.D., Daly M.J., Devlin B., Roeder K., State M.W. (2015). Insights into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci. Neuron, 87: 1215–1233.
Search in Google Scholar Back to article
Sironen A., Uimari P., Venhoranta H., Andersson M., Vilkki J. (2011). An exonic insertion within Tex14 gene causes spermatogenic arrest in pigs. BMC Genomics, 12: 591.
Search in Google Scholar Back to article
Skinner B.M., Sargent C.A., Churcher C., Hunt T., Herrero J., Loveland J.E., Dunn M., Louzada S., Fu B., Chow W., Gilbert J., Austin-Guest S., Beal K., Carvalho-Silva D., Cheng W., Gordon D., Grafham D., Hardy M., Harley J., Hauser H., Howden P., Howe K., Lachani K., Ellis P.J.I., Kelly D., Kerry G., Kerwin J., Ng B.L., Threadgold G., Wileman T., Wood J.M.D., Yang F., Harrow J., Affara N.A., Tyler-Smith C. (2016). The pig X and Y Chromosomes: structure, sequence, and evolution. Genome Res., 26: 130–139.
Search in Google Scholar Back to article
Soto D.C., Uribe-Salazar J.M., Shew C.J., Sekar A., McGinty S.P., Dennis M.Y. (2023). Genomic structural variation: A complex but important driver of human evolution. Am. J. Biol. Anthropol., 181: 118–144.
Search in Google Scholar Back to article
Stadler Z.K., Esposito D., Shah S., Vijai J., Yamrom B., Levy D., Lee Y., Kendall J., Leotta A., Ronemus M., Hansen N., Sarrel K., Rau-Murthy R., Schrader K., Kauff N., Klein R.J., Lipkin S.M., Murali R., Robson M., Sheinfeld J., Feldman D., Bosl G., Norton L., Wigler M., Offit K. (2012). Rare De Novo Germline Copy-Number Variation in Testicular Cancer. Am. J. Hum. Genet., 91: 379–383.
Search in Google Scholar Back to article
Steensma M.J., Lee Y.L., Bouwman A.C., Pita Barros C., Derks M.F.L., Bink M.C.A.M., Harlizius B., Huisman A.E., Crooijmans R.P.M.A., Groenen M.A.M., Mulder H.A., Rochus C.M. (2023). Identification and characterisation of de novo germline structural variants in two commercial pig lines using trio-based whole genome sequencing. BMC Genomics, 24: 208.
Search in Google Scholar Back to article
Svärd A.A., Viberg E., Von Platen I., Jönsson I., Lundgren M., on behalf of the DiPiS study group, Ramelius A., Andersson C., Bennet R., Ask M., Bremer J., Brundin C., Cilio C., Elding Larsson H., Hansson C., Hansson G., Ivarsson S., Jonsdottir B., Jonsson I., Lindberg B., Lernmark B., Lernmark Å., Melin J., Lundgren M., Carlsson A., Cedervall E., Jönsson B., Larsson K., Neiderud J. (2025). Feasibility of extracting usable DNA from blood samples stored up to 21 years in the DiPiS study. Sci. Rep., 15: 25637.
Search in Google Scholar Back to article
Tang Y.-C., Amon A. (2013). Gene copy-number alterations: a cost-benefit analysis. Cell, 152: 394–405.
Search in Google Scholar Back to article
The Bovine Genome Sequencing and Analysis Consortium, Elsik C.G., Tellam R.L., Worley K.C., Gibbs R.A., Muzny D.M., Weinstock G.M., Adelson D.L., Eichler E.E., Elnitski L., Guigó R., Hamernik D.L., Kappes S.M., Lewin H.A., Lynn D.J., Nicholas F.W., Reymond A., Rijnkels M., Skow L.C., Zdobnov E.M., Schook L., Womack J., Alioto T., Antonarakis S.E., Astashyn A., Chapple C.E., Chen H.-C., Chrast J., Câmara F., Ermolaeva O., Henrichsen C.N., Hlavina W., Kapustin Y., Kiryutin B., Kitts P., Kokocinski F., Landrum M., Maglott D., Pruitt K., Sapojnikov V., Searle S.M., Solovyev V., Souvorov A., Ucla C., Wyss C., Anzola J.M., Gerlach D., Elhaik E., Graur D., Reese J.T., Edgar R.C., McEwan J.C., Payne G.M., Raison J.M., Junier T., Kriventseva E.V., Eyras E., Plass M., Donthu R., Larkin D.M., Reecy J., Yang M.Q., Chen L., Cheng Z., Chitko-McKown C.G., Liu G.E., Matukumalli L.K., Song J., Zhu B., Bradley D.G., Brinkman F.S.L., Lau L.P.L., Whiteside M.D., Walker A., Wheeler T.T., Casey T., German J.B., Lemay D.G., Maqbool N.J., Molenaar A.J., Seo S., Stothard P., Baldwin C.L., Baxter R., Brinkmeyer-Langford C.L., Brown W.C., Childers C.P., Connelley T., Ellis S.A., Fritz K., Glass E.J., Herzig C.T.A., Iivanainen A., Lahmers K.K., Bennett A.K., Dickens C.M., Gilbert J.G.R., Hagen D.E., Salih H., Aerts J., Caetano A.R., Dalrymple B., Garcia J.F., Gill C.A., Hiendleder S.G., Memili E., Spurlock D., Williams J.L., Alexander L., Brownstein M.J., Guan L., Holt R.A., Jones S.J.M., Marra M.A., Moore R., Moore S.S., Roberts A., Taniguchi M., Waterman R.C., Chacko J., Chandrabose M.M., Cree A., Dao M.D., Dinh H.H., Gabisi R.A., Hines S., Hume J., Jhangiani S.N., Joshi V., Kovar C.L., Lewis L.R., Liu Y., Lopez J., Morgan M.B., Nguyen N.B., Okwuonu G.O., Ruiz S.J., Santibanez J., Wright R.A., Buhay C., Ding Y., Dugan-Rocha S., Herdandez J., Holder M., Sabo A., Egan A., Goodell J., Wilczek-Boney K., Fowler G.R., Hitchens M.E., Lozado R.J., Moen C., Steffen D., Warren J.T., Zhang J., Chiu R., Schein J.E., Durbin K.J., Havlak P., Jiang H., Liu Y., Qin X., Ren Y., Shen Y., Song H., Bell S.N., Davis C., Johnson A.J., Lee S., Nazareth L.V., Patel B.M., Pu L.-L., Vattathil S., Williams R.L., Curry S., Hamilton C., Sodergren E., Wheeler D.A., Barris W., Bennett G.L., Eggen A., Green R.D., Harhay G.P., Hobbs M., Jann O., Keele J.W., Kent M.P., Lien S., McKay S.D., McWilliam S., Ratnakumar A., Schnabel R.D., Smith T., Snelling W.M., Sonstegard T.S., Stone R.T., Sugimoto Y., Takasuga A., Taylor J.F., Van Tassell C.P., MacNeil M.D., Abatepaulo A.R.R., Abbey C.A., Ahola V., Almeida I.G., Amadio A.F., Anatriello E., Bahadue S.M., Biase F.H., Boldt C.R., Carroll J.A., Carvalho W.A., Cervelatti E.P., Chacko E., Chapin J.E., Cheng Y., Choi J., Colley A.J., De Campos T.A., De Donato M., Santos I.K.F.D.M., De Oliveira C.J.F., Deobald H., Devinoy E., Donohue K.E., Dovc P., Eberlein A., Fitzsimmons C.J., Franzin A.M., Garcia G.R., Genini S., Gladney C.J., Grant J.R., Greaser M.L., Green J.A., Hadsell D.L., Hakimov H.A., Halgren R., Harrow J.L., Hart E.A., Hastings N., Hernandez M., Hu Z.-L., Ingham A., Iso-Touru T., Jamis C., Jensen K., Kapetis D., Kerr T., Khalil S.S., Khatib H., Kolbehdari D., Kumar C.G., Kumar D., Leach R., Lee J.C.-M., Li C., Logan K.M., Malinverni R., Marques E., Martin W.F., Martins N.F., Maruyama S.R., Mazza R., McLean K.L., Medrano J.F., Moreno B.T., Moré D.D., Muntean C.T., Nandakumar H.P., Nogueira M.F.G., Olsaker I., Pant S.D., Panzitta F., Pastor R.C.P., Poli M.A., Poslusny N., Rachagani S., Ranganathan S., Razpet A., Riggs P K., Rincon G., Rodriguez-Osorio N., Rodriguez-Zas S.L., Romero N.E., Rosenwald A., Sando L., Schmutz S.M., Shen L., Sherman L., Southey B.R., Lutzow Y.S., Sweedler J.V., Tammen I., Telugu B.P.V.L., Urbanski J.M., Utsunomiya Y.T., Verschoor C.P., Waardenberg A.J., Wang Z., Ward R., Weikard R., Welsh T.H., White S. N., Wilming L.G., Wunderlich K.R., Yang J., Zhao F.-Q. (2009). The Genome Sequence of Taurine Cattle: A Window to Ruminant Biology and Evolution. Science, 324: 522–528.
Search in Google Scholar Back to article
The Gene Ontology Consortium, Aleksander S.A., Balhoff J., Carbon S., Cherry J.M., Drabkin H.J., Ebert D., Feuermann M., Gaudet P., Harris N.L., Hill D.P., Lee R., Mi H., Moxon S., Mungall C.J., Muruganugan A., Mushayahama T., Sternberg P.W., Thomas P.D., Van Auken K., Ramsey J., Siegele D.A., Chisholm R.L., Fey P., Aspromonte M.C., Nugnes M.V., Quaglia F., Tosatto S., Giglio M., Nadendla S., Antonazzo G., Attrill H., Dos Santos G., Marygold S., Strelets V., Tabone C.J., Thurmond J., Zhou P., Ahmed S.H., Asanitthong P., Luna Buitrago D., Erdol M.N., Gage M.C., Ali Kadhum M., Li K.Y.C., Long M., Michalak A., Pesala A., Pritazahra A., Saverimuttu S.C.C., Su R., Thurlow K.E., Lovering R.C., Logie C., Oliferenko S., Blake J., Christie K., Corbani L., Dolan M.E., Drabkin H.J., Hill D.P., Ni L., Sitnikov D., Smith C., Cuzick A., Seager J., Cooper L., Elser J., Jaiswal P., Gupta P., Jaiswal P., Naithani S., Lera-Ramirez M., Rutherford K., Wood V., De Pons J.L., Dwinell M.R., Hayman G.T., Kaldunski M.L., Kwitek A.E., Laulederkind S.J.F., Tutaj M.A., Vedi M., Wang S.-J., D'Eustachio P., Aimo L., Axelsen K., Bridge A., Hyka-Nouspikel N., Morgat A., Aleksander S.A., Cherry J.M., Engel S.R., Karra K., Miyasato S.R., Nash R.S., Skrzypek M.S., Weng S., Wong E.D., Bakker E., Berardini T.Z., Reiser L., Auchincloss A., Axelsen K., Argoud-Puy G., Blatter M.-C., Boutet E., Breuza L., Bridge A., Casals-Casas C., Coudert E., Estreicher A., Livia Famiglietti M., Feuermann M., Gos A., Gruaz-Gumowski N., Hulo C., Hyka-Nouspikel N., Jungo F., Le Mercier P., Lieberherr D., Masson P., Morgat A., Pedruzzi I., Pourcel L., Poux S., Rivoire C., Sundaram S., Bateman A., Bowler-Barnett E., Bye-A-Jee H., Denny P., Ignatchenko A., Ishtiaq R., Lock A., Lussi Y., Magrane M., Martin M.J., Orchard S., Raposo P., Speretta E., Tyagi N., Warner K., Zaru R., Diehl A. D., Lee R., Chan J., Diamantakis S., Raciti D., Zarowiecki M., Fisher M., James-Zorn C., Ponferrada V., Zorn A., Ramachandran S., Ruzicka L., Westerfield M., (2023). The Gene Ontology knowledgebase in 2023. Genetics, 224: iyad031.
Search in Google Scholar Back to article
Tizaoui K. (2018). De novo vs. inherited copy number variations in multiple sclerosis susceptibility. Cell. Mol. Immunol., 15: 812–814.
Search in Google Scholar Back to article
Toft M., Ross O. A. (2010). Copy number variation in Parkinson's disease. Genome Med., 2: 62.
Search in Google Scholar Back to article
Wadhawan I., Hai Y., Foyouzi Yousefi N., Guo X., Graham J.M., Rosenfeld J.A. (2020). De novo copy number variants and parental age: Is there an association? Eur. J. Med. Genet., 63: 103829.
Search in Google Scholar Back to article
Walters E.M., Prather R.S. (2013). Advancing swine models for human health and diseases. Mo. Med., 110: 212–215.
Search in Google Scholar Back to article
Wang J., Jiang J., Fu W., Jiang L., Ding X., Liu J.-F., Zhang Q. (2012). A genome-wide detection of copy number variations using SNP genotyping arrays in swine. BMC Genomics, 13: 273.
Search in Google Scholar Back to article
Wang J., Jiang J., Wang H., Kang H., Zhang Q., Liu J.-F. (2014). Enhancing Genome-Wide Copy Number Variation Identification by High Density Array CGH Using Diverse Resources of Pig Breeds. PLoS ONE, 9: e87571.
Search in Google Scholar Back to article
Wang J., Wang H., Jiang J., Kang H., Feng X., Zhang Q., Liu, J.-F. (2013). Identification of Genome-Wide Copy Number Variations among Diverse Pig Breeds Using SNP Genotyping Arrays. PLoS ONE, 8: e68683.
Search in Google Scholar Back to article
Wang L., Xu L., Liu X., Zhang T., Li N., Hay E.H., Zhang Y., Yan H., Zhao K., Liu G.E., Zhang L., Wang, L. (2015). Copy number variation-based genome wide association study reveals additional variants contributing to meat quality in Swine. Sci. Rep., 5: 12535.
Search in Google Scholar Back to article
Wang Z., Chen Q., Liao R., Zhang Z., Zhang X., Liu X., Zhu M., Zhang W., Xue M., Yang H., Zheng Y., Wang Q., Pan Y. (2017). Genome-wide genetic variation discovery in Chinese Taihu pig breeds using next generation sequencing. Anim. Genet., 48: 38–47.
Search in Google Scholar Back to article
Wen Q., Wang X., Zhang H., Liu X., Xu Z. (2022). Distribution and transmission of copy number variations of uncertain significance in 105 trios. Mol. Genet. Genomic Med., 10: e2030.
Search in Google Scholar Back to article
Xu C., Zhang W., Jiang Y., Zhou M., Liu L., Su S., Li X., Wang C. (2023). Genome-Wide Detection and Analysis of Copy Number Variation in Anhui Indigenous and Western Commercial Pig Breeds Using Porcine 80K SNP BeadChip. Genes, 14: 654.
Search in Google Scholar Back to article
Yang L., Li X., Zhuang Z., Zhou S., Wu J., Xu C., Ruan D., Qiu Y., Zhao H., Zheng E., Cai G., Wu Z., Yang J. (2023). Genome-Wide Association Study Identifies the Crucial Candidate Genes for Teat Number in Crossbred Commercial Pigs. Animals, 13: 1880.
Search in Google Scholar Back to article
Ye K., Schulz M.H., Long Q., Apweiler R., Ning Z. (2009). Pindel: a pattern growth approach to detect break points of large deletions and medium sized insertions from paired-end short reads. Bioinformatics, 25: 2865–2871.
Search in Google Scholar Back to article
Yin H., Ma H., Hussain S., Zhang H., Xie X., Jiang L., Jiang X., Iqbal F., Bukhari I., Jiang H., Ali A., Zhong L., Li T., Fan S., Zhang B., Gao J., Li Y., Nazish J., Khan T., Khan M., Zubair M., Hao Q., Fang H., Huang J., Huleihel M., Sha J., Pandita T.K., Zhang Y., Shi Q. (2019). A homozygous FANCM frameshift pathogenic variant causes male infertility. Genet. Med., 21: 62–70.
Search in Google Scholar Back to article
Zhang C., Yang H., Xu Q., Liu M., Chao X., Chen J., Zhou B. (2024). Genome-Wide Analysis Reveals Copy Number Variant Gene TGFBR3 Regulates Pig Back Fat Deposition. Animals, 14: 2657.
Search in Google Scholar Back to article
Zhang C., Zhao J., Guo Y., Xu Q., Liu M., Cheng M., Chao X., Schinckel A.P., Zhou B. (2022). Genome-Wide Detection of Copy Number Variations and Evaluation of Candidate Copy Number Polymorphism Genes Associated With Complex Traits of Pigs. Front. Vet. Sci., 9: 909039.
Search in Google Scholar Back to article
Zheng X., Zhao P., Yang K., Ning C., Wang H., Zhou L., Liu J. (2020). CNV analysis of Meishan pig by next-generation sequencing and effects of AHR gene CNV on pig reproductive traits. J. Anim. Sci. Biotechnol., 11: 42.
Search in Google Scholar Back to article
Zhuang Z., Li K., Yang K., Gao G., Li Z., Zhu X., Zhao Y. (2024). Genome-Wide Association Study Reveals Novel Candidate Genes Influencing Semen Traits in Landrace Pigs. Animals, 14: 1839.
Search in Google Scholar Back to article

Trios-based inquiry into de novo copy number variants in the swine genome

Abstract

Paradigm

My account