{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T20:51:30Z","timestamp":1780433490762,"version":"3.54.1"},"reference-count":40,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,2,12]],"date-time":"2022-02-12T00:00:00Z","timestamp":1644624000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Copy number variations (CNVs) have many forms of variation structure, and they play an important role in the research of variety diversity, biological evolution and disease correlation. Since CNVs have a greater impact on gene regulation and expression, more studies are being finalized on CNVs in important livestock and poultry species. The protein phosphatase 3 catalytic subunit alpha (PPP3CA) is a key candidate gene involved in the goat fecundity trait, and has important effects on precocious puberty, estrogen signal transduction pathways and oocyte meiosis. Additionally, PPP3CA also has a dephosphorylation effect in the process of spermatogonial stem cell meiosis and spermatogenesis. So far, there is no research on the relationship between the copy number variations of the PPP3CA gene and reproduction traits. Therefore, the purpose of this study was to determine the association between copy number variations in the goat PPP3CA gene and litter size and semen quality in Shaanbei white cashmere goats (SBWC) (n = 353) and Guizhou Heima goats (n = 64). Based on the association analysis, the results showed that only CNV1 and CNV2 within the PPP3CA gene were distinctly related to the first-birth litter size in female goats (p = 7.6802 \u00d7 10\u221211; p = 5.0895 \u00d7 10\u22129, respectively) and they were also significantly associated with the semen quality of SBWC goats (p &lt; 0.05). In addition, individuals with Loss genotypes demonstrated better phenotypic performance compared to those with other types. Therefore, CNV1 and CNV2 of the PPP3CA gene are potentially useful for breeding, as they are linked to important goat reproduction traits.<\/jats:p>","DOI":"10.3390\/ani12040445","type":"journal-article","created":{"date-parts":[[2022,2,13]],"date-time":"2022-02-13T20:32:30Z","timestamp":1644784350000},"page":"445","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Investigation of Copy Number Variations (CNVs) of the Goat PPP3CA Gene and Their Effect on Litter Size and Semen Quality"],"prefix":"10.3390","volume":"12","author":[{"given":"Yangyang","family":"Bai","sequence":"first","affiliation":[{"name":"Key Laboratory of Animal Genetics, College of Animal Science and Technology, Breeding and Reproduction of Shaanxi Province, Northwest A&F University, Yangling 712100, China"},{"name":"Shaanxi Provincial Engineering and Technology Research Center of Cashmere Goats, Yulin University, Yulin 719000, China"},{"name":"Life Science Research Center, Yulin University, Yulin 719000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taiyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Genetics, College of Animal Science and Technology, Breeding and Reproduction of Shaanxi Province, Northwest A&F University, Yangling 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Genetics, College of Animal Science and Technology, Breeding and Reproduction of Shaanxi Province, Northwest A&F University, Yangling 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Congliang","family":"Wang","sequence":"additional","affiliation":[{"name":"Shaanxi Provincial Engineering and Technology Research Center of Cashmere Goats, Yulin University, Yulin 719000, China"},{"name":"Life Science Research Center, Yulin University, Yulin 719000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengang","family":"Guo","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Genetics, College of Animal Science and Technology, Breeding and Reproduction of Shaanxi Province, Northwest A&F University, Yangling 712100, China"},{"name":"Bijie Animal Husbandry and Veterinary Science Research Institute, Bijie 551700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanying","family":"Pan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Genetics, College of Animal Science and Technology, Breeding and Reproduction of Shaanxi Province, Northwest A&F University, Yangling 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haijing","family":"Zhu","sequence":"additional","affiliation":[{"name":"Shaanxi Provincial Engineering and Technology Research Center of Cashmere Goats, Yulin University, Yulin 719000, China"},{"name":"Life Science Research Center, Yulin University, Yulin 719000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianyong","family":"Lan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Genetics, College of Animal Science and Technology, Breeding and Reproduction of Shaanxi Province, Northwest A&F University, Yangling 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1083\/jcb.106.5.1625","article-title":"Identification, characterization, and functional correlation of calmodulin-dependent protein phosphatase in sperm","volume":"106","author":"Tash","year":"1988","journal-title":"J. Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/s41431-018-0254-8","article-title":"Novel calcineurin A (PPP3CA) variant associated with epilepsy, constitutive enzyme activation and downregulation of protein expression","volume":"27","author":"Rydzanicz","year":"2019","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"107561","DOI":"10.1016\/j.compbiolchem.2021.107561","article-title":"Identification of calcineurin as a predictor of oocyte quality and fertilization competence based on microarray data","volume":"94","author":"Aflatoonian","year":"2021","journal-title":"Comput. Biol. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1111\/cge.13979","article-title":"PPP3CA truncating variants clustered in the regulatory domain cause early-onset refractory epilepsy","volume":"100","author":"Panneerselvam","year":"2021","journal-title":"Clin Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1007\/s13258-020-00937-5","article-title":"Genome-wide association analysis reveals the genetic locus for high reproduction trait in Chinese Arbas cashmere goat","volume":"42","author":"Islam","year":"2020","journal-title":"Genes Genom."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"234","DOI":"10.4238\/2015.January.16.7","article-title":"Study of lipid metabolism-related genes as candidate genes of sexual precocity in Nellore cattle","volume":"14","author":"Dias","year":"2015","journal-title":"Genet. Mol. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5517","DOI":"10.1007\/s11033-019-04904-6","article-title":"Selection signatures of litter size in Dazu black goats based on a whole genome sequencing mixed pools strategy","volume":"46","author":"E","year":"2019","journal-title":"Mol. Biol. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2346","DOI":"10.3390\/ijms15022346","article-title":"Molecular cloning, structural analysis and tissue expression of protein phosphatase 3 catalytic subunit alpha isoform (PPP3CA) gene in Tianfu goat muscle","volume":"15","author":"Wan","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1007\/s00210-017-1411-2","article-title":"Calcineurin inhibitors regulate fibroblast growth factor 23 (FGF23) synthesis","volume":"390","author":"Gekle","year":"2017","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1071\/RD20337","article-title":"Deletion mutation within the goat PPP3CA gene identified by GWAS significantly affects litter size","volume":"33","author":"Bai","year":"2021","journal-title":"Reprod. Fertil. Dev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1093\/toxsci\/kfm229","article-title":"FK506, a calcineurin inhibitor, prevents cadmium-induced testicular toxicity in mice","volume":"100","author":"Martin","year":"2007","journal-title":"Toxicol. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"37659","DOI":"10.1074\/jbc.M112.392803","article-title":"Dynamin regulates specific membrane fusion events necessary for acrosomal exocytosis in mouse spermatozoa","volume":"287","author":"Reid","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"35084","DOI":"10.1038\/srep35084","article-title":"Dynamin 2 is essential for mammalian spermatogenesis","volume":"6","author":"Redgrove","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Di Gerlando, R., Mastrangelo, S., Moscarelli, A., Tolone, M., Sutera, A.M., Portolano, B., and Sardina, M.T. (2020). Genomic structural diversity in local goats: Analysis of copy-number variations. Animals, 10.","DOI":"10.3390\/ani10061040"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5115","DOI":"10.1016\/j.ygeno.2020.09.029","article-title":"Goat sperm associated antigen 17 protein gene (SPAG17): Small and large fragment genetic variation detection, association analysis, and mRNA expression in gonads","volume":"112","author":"Zhang","year":"2020","journal-title":"Genomics"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1016\/j.ygeno.2020.10.012","article-title":"Genomic sequencing analysis reveals copy number variations and their associations with economically important traits in beef cattle","volume":"113","author":"Yang","year":"2021","journal-title":"Genomics"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1126\/science.1098918","article-title":"Large-scale copy number polymorphism in the human genome","volume":"305","author":"Sebat","year":"2004","journal-title":"Science"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1016\/j.ygeno.2019.08.018","article-title":"Genome-wide CNV analysis revealed variants associated with growth traits in African indigenous goats","volume":"112","author":"Liu","year":"2020","journal-title":"Genomics"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4934","DOI":"10.1016\/j.ygeno.2020.09.007","article-title":"Copy number variation analysis reveals variants associated with milk production traits in dairy goats","volume":"112","author":"Kang","year":"2020","journal-title":"Genomics"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Li, L., Yang, P., Shi, S., Zhang, Z., Shi, Q., Xu, J., He, H., Lei, C., Wang, E., and Chen, H. (2020). Association analysis to copy number variation (CNV) of Opn4 gene with growth traits of goats. Animals, 10.","DOI":"10.3390\/ani10030441"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Wang, Z., Wang, C., Guo, Y., She, S., Wang, B., Jiang, Y., Bai, Y., Song, X., Li, L., and Shi, L. (2020). Screening of deletion variants within the goat PRDM6 gene and its effects on growth traits. Animals, 10.","DOI":"10.3390\/ani10020208"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"144519","DOI":"10.1016\/j.gene.2020.144519","article-title":"Copy number variation of CADM2 gene revealed its association with growth traits across Chinese Capra hircus (goat) populations","volume":"741","author":"Xu","year":"2020","journal-title":"Gene"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"758705","DOI":"10.3389\/fvets.2021.758705","article-title":"Detection of mRNA expression and copy number variations within the goat FecB gene associated with litter size","volume":"8","author":"Bi","year":"2021","journal-title":"Front. Vet. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.theriogenology.2020.01.079","article-title":"Genetic effects of DSCAML1 identified in genome-wide association study revealing strong associations with litter size and semen quality in goat (Capra hircus)","volume":"146","author":"Wang","year":"2020","journal-title":"Theriogenology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.theriogenology.2020.02.025","article-title":"Goat DNMT3B: An indel mutation detection, association analysis with litter size and mRNA expression in gonads","volume":"147","author":"Hui","year":"2020","journal-title":"Theriogenology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e13995","DOI":"10.1111\/and.13995","article-title":"Semen quality and total microbial load: An association study in important Indian Goat breeds during different seasons","volume":"53","author":"Gangwar","year":"2021","journal-title":"Andrologia"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1017\/S002185960003029X","article-title":"Nigrosin eosin as a stain for differentiating live and dead spermatozoa","volume":"48","author":"Campbell","year":"1956","journal-title":"J. Agric. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2598","DOI":"10.1017\/S1751731118000320","article-title":"Sedation or anaesthesia decrease the stress response to electroejaculation and improve the quality of the collected semen in goat bucks","volume":"12","author":"Crosignani","year":"2018","journal-title":"Animal"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1530\/jrf.0.0700219","article-title":"Development of an assay to assess the functional integrity of the human sperm membrane and its relationship to other semen characteristics","volume":"70","author":"Jeyendran","year":"1984","journal-title":"J. Reprod. Fertil."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.3389\/fgene.2019.01169","article-title":"Towards the complete goat pan-genome by recovering missing genomic segments from the reference genome","volume":"10","author":"Li","year":"2019","journal-title":"Front. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1080\/10495398.2019.1635137","article-title":"Copy number variation of MYLK4 gene and its growth traits of Capra hircus (goat)","volume":"31","author":"Shi","year":"2020","journal-title":"Anim. Biotechnol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/gigascience\/gix115","article-title":"CNVcaller: Highly efficient and widely applicable software for detecting copy number variations in large populations","volume":"6","author":"Wang","year":"2017","journal-title":"Gigascience"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.theriogenology.2021.11.023","article-title":"Novel InDel variations of the Cry2 gene are associated with litter size in Australian White sheep","volume":"179","author":"Huang","year":"2022","journal-title":"Theriogenology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"648256","DOI":"10.3389\/fgene.2021.648256","article-title":"Goat AKAP12: Indel mutation detection, association analysis with litter size and alternative splicing variant expression","volume":"12","author":"Kang","year":"2021","journal-title":"Front. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Bai, Y., Yuan, R., Luo, Y., Kang, Z., Zhu, H., Qu, L., Lan, X., and Song, X. (2021). Exploration of genetic variants within the goat A-Kinase anchoring protein 12 (AKAP12) gene and their effects on growth traits. Animals, 11.","DOI":"10.3390\/ani11072090"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1126\/science.aad0836","article-title":"Sperm calcineurin inhibition prevents mouse fertility with implications for male contraceptive","volume":"350","author":"Miyata","year":"2015","journal-title":"Science"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1152\/physrev.2000.80.4.1483","article-title":"(2000). Calcineurin: Form and function","volume":"80","author":"Rusnak","year":"2000","journal-title":"Physiol. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1096\/fj.201902163R","article-title":"Roles of glycogen synthase kinase 3 alpha and calcineurin in regulating the ability of sperm to fertilize eggs","volume":"34","author":"Dey","year":"2020","journal-title":"FASEB J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1111\/rda.13796","article-title":"Indel variants within the PRL and GHR genes associated with sheep litter size","volume":"55","author":"Akhatayeva","year":"2020","journal-title":"Reprod. Domest. Anim."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.theriogenology.2019.01.014","article-title":"Goat membrane associated ring-CH-type finger 1 (MARCH1) mRNA expression and association with litter size","volume":"128","author":"Kang","year":"2019","journal-title":"Theriogenology"}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/12\/4\/445\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:18:16Z","timestamp":1760134696000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/12\/4\/445"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,12]]},"references-count":40,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["ani12040445"],"URL":"https:\/\/doi.org\/10.3390\/ani12040445","relation":{},"ISSN":["2076-2615"],"issn-type":[{"value":"2076-2615","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,12]]}}}