{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T07:15:49Z","timestamp":1787901349859,"version":"build-2784847793"},"reference-count":36,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T00:00:00Z","timestamp":1745971200000},"content-version":"vor","delay-in-days":119,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"STI 2030 \u2013 Major Projects","award":["2023ZD04045"],"award-info":[{"award-number":["2023ZD04045"]}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program","doi-asserted-by":"publisher","award":["2021YFD1301105"],"award-info":[{"award-number":["2021YFD1301105"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Postdoctoral Fellowship Program","award":["2024M751448"],"award-info":[{"award-number":["2024M751448"]}]},{"name":"Fundamental Research Funds","award":["KYZZ2024001"],"award-info":[{"award-number":["KYZZ2024001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Milk is an essential source of nutrition for preweaning piglets. Therefore, in the breeding process, sows were expected to have sufficient teats to suckle their piglets. However, in Danish Landrace and Large White pigs, the number of piglets born currently exceeds the number of teats, making it urgent to select and breed for an increased teat number. In this study, the samples of 491 Danish Landrace pigs and 1,047 Danish Large White pigs with teat number phenotype were used to perform genome-wide association studies to identify SNPs associated with total teat number (TTN) based on SNP-chip data and data imputed to the level of whole-genome sequencing (iWGS), respectively. In Landrace pigs, the most significant SNP on SSC10 explains 5.14% of the phenotypic variance, while in Large White pigs, the most significant SNP on SSC7 explains 4.46% of the phenotypic variance. Additionally, linkage disequilibrium and linkage analysis (LDLA) were used to refine the regions of QTLs on SSC10 to 2.89 to 5.43\u00a0Mb in Danish Landrace pigs and to 96.00 to 97.95\u00a0Mb on SSC7 in Danish Large White pigs, respectively. To maximize the utility of information from 2 populations, meta-analysis was conducted across multiple populations. A total of 12 protein-coding genes were identified within the candidate QTL regions determined by LDLA and meta-analysis. To supplement the candidate gene set, transcriptome-wide association studies (TWAS) based on embryo and placenta tissues identified 7 protein-coding genes associated with TTN in Landrace and Large White pigs. Phenome-wide association studies (PheWAS) query was conducted for all the above genes, revealing that nearly all of them are associated with teat number traits. Additionally, some genes showed strong associations with carcass traits, suggesting a potential association between teat number and carcass traits. Through functional annotation and integrated analysis, BRINP3, LIN52, ABCD4, and UBE3B were determined as the functional candidate genes regulating TTN. These findings lay the foundation for identifying the genetic loci regulating teat number in Danish pigs, as well as for their molecular breeding.<\/jats:p>","DOI":"10.1093\/jas\/skaf145","type":"journal-article","created":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T23:20:19Z","timestamp":1746055219000},"source":"Crossref","is-referenced-by-count":3,"title":["Multiple association studies identify 3 novel candidate genes for teat number trait in Danish Landrace and Large White pigs: <i>BRINP3<\/i>, <i>LIN52<\/i>, and <i>UBE3B<\/i>"],"prefix":"10.1093","volume":"103","author":[{"given":"Zijian","family":"Qiu","sequence":"first","affiliation":[{"name":"Key Laboratory (Nanjing) for Evaluation and Utilization of Pigs Resources, Ministry of Agriculture and Rural Affairs , Nanjing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanzhen","family":"Yin","sequence":"additional","affiliation":[{"name":"Key Laboratory (Nanjing) for Evaluation and Utilization of Pigs Resources, Ministry of Agriculture and Rural Affairs , Nanjing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruihua","family":"Huang","sequence":"additional","affiliation":[{"name":"Key Laboratory (Nanjing) for Evaluation and Utilization of Pigs Resources, Ministry of Agriculture and Rural Affairs , Nanjing ,","place":["China"]},{"name":"College of Animal Science & Technology, Institute of Swine Science, Nanjing Agricultural University , Nanjing ,","place":["China"]},{"name":"Huaian Academy, Nanjing Agricultural University , Huaian ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Laboratory (Nanjing) for Evaluation and Utilization of Pigs Resources, Ministry of Agriculture and Rural Affairs , Nanjing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory (Nanjing) for Evaluation and Utilization of Pigs Resources, Ministry of Agriculture and Rural Affairs , Nanjing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiyue","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory (Nanjing) for Evaluation and Utilization of Pigs Resources, Ministry of Agriculture and Rural Affairs , Nanjing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenxi","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory (Nanjing) for Evaluation and Utilization of Pigs Resources, Ministry of Agriculture and Rural Affairs , Nanjing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2148-2435","authenticated-orcid":false,"given":"Pinghua","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory (Nanjing) for Evaluation and Utilization of Pigs Resources, Ministry of Agriculture and Rural Affairs , Nanjing ,","place":["China"]},{"name":"College of Animal Science & Technology, Institute of Swine Science, Nanjing Agricultural University , Nanjing ,","place":["China"]},{"name":"Huaian Academy, Nanjing Agricultural University , Huaian ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingbo","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory (Nanjing) for Evaluation and Utilization of Pigs Resources, Ministry of Agriculture and Rural Affairs , Nanjing ,","place":["China"]},{"name":"College of Animal Science & Technology, Institute of Swine Science, Nanjing Agricultural University , Nanjing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,4,30]]},"reference":[{"key":"2025053012070199400_CIT0001","doi-asserted-by":"publisher","first-page":"38","DOI":"10.3390\/ani8030038","article-title":"A review of success factors for piglet fostering in lactation","volume":"8","author":"Alexopoulos","year":"2018","journal-title":"Animals (Basel)"},{"key":"2025053012070199400_CIT0002","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1111\/age.13095","article-title":"Single-marker and haplotype-based genome-wide association studies for the number of teats in two heavy pig breeds","volume":"52","author":"Bovo","year":"2021","journal-title":"Anim. Genet"},{"key":"2025053012070199400_CIT0003","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.1086\/521987","article-title":"Rapid and accurate haplotype phasing and missing-data inference for whole-genome association studies by use of localized haplotype clustering","volume":"81","author":"Browning","year":"2007","journal-title":"Am. J. Hum. Genet"},{"key":"2025053012070199400_CIT0004","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1016\/j.ajhg.2018.07.015","article-title":"A one-penny imputed genome from next-generation reference panels","volume":"103","author":"Browning","year":"2018","journal-title":"Am. J. Hum. Genet"},{"key":"2025053012070199400_CIT0005","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s13742-015-0047-8","article-title":"Second-generation PLINK: rising to the challenge of larger and richer datasets","volume":"4","author":"Chang","year":"2015","journal-title":"GigaScience"},{"key":"2025053012070199400_CIT0006","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1007\/s11302-021-09795-6","article-title":"ENTPD5: Identification of splicing variants and their impact on cancer survival","volume":"17","author":"de Campos","year":"2021","journal-title":"Purinergic Signal"},{"key":"2025053012070199400_CIT0007","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1111\/age.13397","article-title":"Genome-wide association analysis revealed new QTL and candidate genes affecting the teat number in Dutch Large White pigs","volume":"55","author":"Deng","year":"2024","journal-title":"Anim. Genet"},{"key":"2025053012070199400_CIT0008","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/1471-2105-15-47","article-title":"PSEUDOMARKER 2.0: efficient computation of likelihoods using NOMAD","volume":"15","author":"Gertz","year":"2014","journal-title":"BMC Bioinf"},{"key":"2025053012070199400_CIT0009","doi-asserted-by":"publisher","first-page":"650370","DOI":"10.3389\/fgene.2021.650370","article-title":"Genome-wide association study for body length, body height, and total teat number in large white pigs","volume":"12","author":"Hong","year":"2021","journal-title":"Front. Genet"},{"key":"2025053012070199400_CIT0010","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/ng.814","article-title":"Variants modulating the expression of a chromosome domain encompassing PLAG1 influence bovine stature","volume":"43","author":"Karim","year":"2011","journal-title":"Nat. Genet"},{"key":"2025053012070199400_CIT0011","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.anireprosci.2005.01.013","article-title":"Effects of teat number on litter size in gilts","volume":"90","author":"Kim","year":"2005","journal-title":"Anim. Reprod. Sci"},{"key":"2025053012070199400_CIT0012","doi-asserted-by":"publisher","first-page":"28889","DOI":"10.1038\/s41598-024-80117-7","article-title":"Examining genotype-phenotype associations of GRAM domain proteins using GWAS, PheWAS and literature review in cattle, human, pig, mouse and chicken","volume":"14","author":"Kunej","year":"2024","journal-title":"Sci. Rep."},{"key":"2025053012070199400_CIT0013","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s12711-017-0289-2","article-title":"Genome-wide association study for conformation traits in three Danish pig breeds","volume":"49","author":"Le","year":"2017","journal-title":"Genet. Sel. Evol"},{"key":"2025053012070199400_CIT0014","doi-asserted-by":"publisher","first-page":"806","DOI":"10.3390\/ani11030806","article-title":"Revealing new candidate genes for teat number relevant traits in duroc pigs using Genome-Wide association studies","volume":"11","author":"Li","year":"2021","journal-title":"Animals (Basel)"},{"key":"2025053012070199400_CIT0015","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/ijms25010451","article-title":"Genome-wide association study meta-analysis elucidates genetic structure and identifies candidate genes of teat number traits in pigs","volume":"25","author":"Li","year":"2023","journal-title":"Int. J. Mol. Sci"},{"key":"2025053012070199400_CIT0016","doi-asserted-by":"publisher","first-page":"e105867","DOI":"10.1371\/journal.pone.0105867","article-title":"A genome-wide association study reveals dominance effects on number of teats in pigs","volume":"9","author":"Lopes","year":"2014","journal-title":"PLoS One"},{"key":"2025053012070199400_CIT0017","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1186\/s12864-020-06826-1","article-title":"Genome-wide identification and comparison of differentially expressed profiles of miRNAs and lncRNAs with associated ceRNA networks in the gonads of Chinese soft-shelled turtle, Pelodiscus sinensis","volume":"21","author":"Ma","year":"2020","journal-title":"BMC Genomics"},{"key":"2025053012070199400_CIT0018","doi-asserted-by":"publisher","first-page":"1719","DOI":"10.1534\/genetics.106.068148","article-title":"DPL-1 DP, LIN-35 Rb and EFL-1 E2F act with the MCD-1 zinc-finger protein to promote programmed cell death in Caenorhabditis elegans","volume":"175","author":"Reddien","year":"2007","journal-title":"Genetics"},{"key":"2025053012070199400_CIT0019","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1038\/nrg2227","article-title":"Cooperation of signalling pathways in embryonic mammary gland development","volume":"8","author":"Robinson","year":"2007","journal-title":"Nat. Rev. Genet"},{"key":"2025053012070199400_CIT0020","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1111\/cts.12522","article-title":"Genome-wide and phenome-wide approaches to understand variable drug actions in electronic health records","volume":"11","author":"Robinson","year":"2018","journal-title":"Clin. Transl. Sci"},{"key":"2025053012070199400_CIT0021","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1101\/gad.181933.111","article-title":"The MuvB complex sequentially recruits B-Myb and FoxM1 to promote mitotic gene expression","volume":"26","author":"Sadasivam","year":"2012","journal-title":"Genes Dev"},{"key":"2025053012070199400_CIT0022","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1016\/j.ajhg.2012.10.010","article-title":"Improved heritability estimation from genome-wide SNPs","volume":"91","author":"Speed","year":"2012","journal-title":"Am. J. Hum. Genet"},{"key":"2025053012070199400_CIT0023","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1186\/s12711-017-0311-8","article-title":"Genome-wide association study and accuracy of genomic prediction for teat number in Duroc pigs using genotyping-by-sequencing","volume":"49","author":"Tan","year":"2017","journal-title":"Genet. Sel. Evol"},{"key":"2025053012070199400_CIT0024","doi-asserted-by":"publisher","first-page":"1","DOI":"10.5713\/ajas.15.0980","article-title":"Identification of loci affecting teat number by genome-wide association studies on three pig populations","volume":"30","author":"Tang","year":"2017","journal-title":"Asian-Australas. J. Anim. Sci"},{"key":"2025053012070199400_CIT0025","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1038\/s41588-023-01585-7","article-title":"A compendium of genetic regulatory effects across pig tissues","volume":"56","author":"Teng","year":"2024","journal-title":"Nat. Genet"},{"key":"2025053012070199400_CIT0026","doi-asserted-by":"publisher","first-page":"272","DOI":"10.3389\/fgene.2019.00272","article-title":"A QTL for number of teats shows breed specific effects on number of vertebrae in pigs: bridging the gap between molecular and quantitative genetics","volume":"10","author":"van Son","year":"2019","journal-title":"Front. Genet"},{"key":"2025053012070199400_CIT0027","doi-asserted-by":"publisher","first-page":"3394","DOI":"10.1038\/s41388-023-02842-z","article-title":"UBE3B promotes breast cancer progression by antagonizing HIF-2alpha degradation","volume":"42","author":"Wang","year":"2023","journal-title":"Oncogene"},{"key":"2025053012070199400_CIT0028","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1038\/s41419-024-06844-x","article-title":"VHL suppresses UBE3B-mediated breast tumor growth and metastasis","volume":"15","author":"Wang","year":"2024","journal-title":"Cell Death Dis"},{"key":"2025053012070199400_CIT0029","doi-asserted-by":"publisher","first-page":"2190","DOI":"10.1093\/bioinformatics\/btq340","article-title":"METAL: fast and efficient meta-analysis of genomewide association scans","volume":"26","author":"Willer","year":"2010","journal-title":"Bioinformatics"},{"key":"2025053012070199400_CIT0030","doi-asserted-by":"publisher","first-page":"3501","DOI":"10.1093\/nar\/gkad074","article-title":"HIBLUP: An integration of statistical models on the BLUP framework for efficient genetic evaluation using big genomic data","volume":"51","author":"Yin","year":"2023","journal-title":"Nucleic Acids Res"},{"key":"2025053012070199400_CIT0031","doi-asserted-by":"publisher","first-page":"D980","DOI":"10.1093\/nar\/gkad1080","article-title":"PigBiobank: a valuable resource for understanding genetic and biological mechanisms of diverse complex traits in pigs","volume":"52","author":"Zeng","year":"2024","journal-title":"Nucleic Acids Res"},{"key":"2025053012070199400_CIT0032","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/1297-9686-32-1-41","article-title":"Genetic parameters and genetic trends in the Chinese x European Tiameslan composite pig line. I. Genetic parameters","volume":"32","author":"Zhang","year":"2000","journal-title":"Genet. Sel. Evol"},{"key":"2025053012070199400_CIT0033","first-page":"97","article-title":"Estimation of genetic parameters of reproductive traits of Tibet pig","volume":"36","author":"Zhang","year":"2009","journal-title":"Chin. Anim. Husb. Vet. Med"},{"key":"2025053012070199400_CIT0034","doi-asserted-by":"publisher","first-page":"2467","DOI":"10.1093\/bioinformatics\/bts348","article-title":"Ancestral haplotype-based association mapping with generalized linear mixed models accounting for stratification","volume":"28","author":"Zhang","year":"2012","journal-title":"Bioinformatics"},{"key":"2025053012070199400_CIT0035","doi-asserted-by":"publisher","first-page":"qzaf006","DOI":"10.1093\/gpbjnl\/qzaf006","article-title":"FarmGTEx TWAS-server: An Interactive Web Server for Customized TWAS Analysis","volume":"11","author":"Zhang","year":"2025","journal-title":"Genom. Proteom. Bioinform."},{"key":"2025053012070199400_CIT0036","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1186\/s12864-020-6742-6","article-title":"Genome-wide association analyses identify known and novel loci for teat number in Duroc pigs using single-locus and multi-locus models","volume":"21","author":"Zhuang","year":"2020","journal-title":"BMC Genomics"}],"container-title":["Journal of Animal Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jas\/advance-article-pdf\/doi\/10.1093\/jas\/skaf145\/63036047\/skaf145.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jas\/article-pdf\/doi\/10.1093\/jas\/skaf145\/63036047\/skaf145.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jas\/article-pdf\/doi\/10.1093\/jas\/skaf145\/63036047\/skaf145.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T16:07:08Z","timestamp":1748621228000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jas\/article\/doi\/10.1093\/jas\/skaf145\/8123224"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025]]},"references-count":36,"URL":"https:\/\/doi.org\/10.1093\/jas\/skaf145","relation":{},"ISSN":["0021-8812","1525-3163"],"issn-type":[{"value":"0021-8812","type":"print"},{"value":"1525-3163","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025]]},"published":{"date-parts":[[2025]]},"article-number":"skaf145"}}