{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T21:07:23Z","timestamp":1780434443536,"version":"3.54.1"},"reference-count":62,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T00:00:00Z","timestamp":1738713600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"earmarked fund for the China Agriculture Research System","award":["CARS-35"],"award-info":[{"award-number":["CARS-35"]}]},{"name":"earmarked fund for the China Agriculture Research System","award":["2022B0202090002"],"award-info":[{"award-number":["2022B0202090002"]}]},{"name":"Guangdong Provincial Key R&amp;D Program","award":["CARS-35"],"award-info":[{"award-number":["CARS-35"]}]},{"name":"Guangdong Provincial Key R&amp;D Program","award":["2022B0202090002"],"award-info":[{"award-number":["2022B0202090002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>High-quality semen is an essential factor for the success of artificial insemination, and revealing the genetic structure of pig semen traits helps improve semen quality. This study aimed to identify candidate genes associated with semen traits in three pig breeds (Duroc, Landrace, and Yorkshire) through weighted GWAS and multi-tissue transcriptome analysis. In this study, to identify candidate genes associated with semen traits in Duroc, Landrace, and Yorkshire, we performed weighted GWAS in four traits (sperm motility, sperm progressive motility, sperm abnormality rate, and total sperm count) using 936 pigs and multi-tissue transcriptome analysis using 34 tissues RNA-seq data of 5457 pigs from FarmGTEx. It was found that 16, 9, and 12 significant SNPs associated with semen traits were identified in Duroc, Landrace, and Yorkshire, with corresponding 7, 5, and 7 candidate genes in these three breeds, respectively, which may be involved in mammal spermatogenesis, testicular function, and male fertility. Moreover, we not only found the same candidate gene DNAI2 as in previous studies but also found two new candidate genes PNLDC1 and RSPH3, which were identified simultaneously in both Landrace and Yorkshire. By integrating the GWAS and multi-tissue transcriptome analysis results, we found that candidate genes associated with semen traits of three pig breeds were highly expressed in the testis tissue. The three genotypes of rs320928244 had significant effects on the expression of the DYNLT1 gene in the testis tissue of Landrace. These results together showed that these candidate genes were mainly related to sperm motility defects. This study helps deepen the understanding of the genetic basis of semen traits and provides a theoretical foundation for improving the semen quality of Duroc, Landrace, and Yorkshire breeds.<\/jats:p>","DOI":"10.3390\/ani15030438","type":"journal-article","created":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T04:15:41Z","timestamp":1738728941000},"page":"438","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Identified Candidate Genes of Semen Trait in Three Pig Breeds Through Weighted GWAS and Multi-Tissue Transcriptome Analysis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6961-9475","authenticated-orcid":false,"given":"Xiaoke","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, National Engineering Research Center for Breeding Swine Industry, Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou 510642, China"},{"name":"State Key Laboratory of Animal Biotech Breeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiting","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, National Engineering Research Center for Breeding Swine Industry, Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8416-9748","authenticated-orcid":false,"given":"Qing","family":"Lin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, National Engineering Research Center for Breeding Swine Industry, Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yahui","family":"Gao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, National Engineering Research Center for Breeding Swine Industry, Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaotian","family":"Qiu","sequence":"additional","affiliation":[{"name":"National Animal Husbandry Service, Beijing 100125, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, National Engineering Research Center for Breeding Swine Industry, Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuihua","family":"Xie","sequence":"additional","affiliation":[{"name":"Agriculture Technology Extension Centre of Guangdong Province, Guangzhou 510520, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.theriogenology.2015.07.009","article-title":"Artificial insemination in pigs today","volume":"85","author":"Knox","year":"2016","journal-title":"Theriogenology"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Zhang, X., Lin, Q., Liao, W., Zhang, W., Li, T., Li, J., Zhang, Z., Huang, X., and Zhang, H. (2023). Identification of new candidate genes related to semen traits in Duroc pigs through weighted single-step GWAS. Animals, 13.","DOI":"10.3390\/ani13030365"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"100472","DOI":"10.1016\/j.animal.2022.100472","article-title":"Genome-wide detection of non-additive quantitative trait loci for semen production traits in beef and dairy bulls","volume":"16","author":"Nagai","year":"2022","journal-title":"Animal"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/978-1-4939-7868-7_4","article-title":"Genome-Wide Association Studies","volume":"1793","author":"Dehghan","year":"2018","journal-title":"Methods Mol. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.anireprosci.2014.10.014","article-title":"A genome-wide association study reveals a novel candidate gene for sperm motility in pigs","volume":"151","author":"Diniz","year":"2014","journal-title":"Anim. Reprod. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s12711-018-0412-z","article-title":"Weighted single-step GWAS and gene network analysis reveal new candidate genes for semen traits in pigs","volume":"50","author":"Marques","year":"2018","journal-title":"Genet. Sel. Evol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/s12711-020-00592-0","article-title":"A systems biology framework integrating GWAS and RNA-seq to shed light on the molecular basis of sperm quality in swine","volume":"52","author":"Godia","year":"2020","journal-title":"Genet. Sel. Evol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Gao, N., Chen, Y., Liu, X., Zhao, Y., Zhu, L., Liu, A., Jiang, W., Peng, X., Zhang, C., and Tang, Z. (2019). Weighted single-step GWAS identified candidate genes associated with semen traits in a Duroc boar population. BMC Genom., 20.","DOI":"10.1186\/s12864-019-6164-5"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.theriogenology.2019.08.031","article-title":"Identifying candidate genes associated with sperm morphology abnormalities using weighted single-step GWAS in a Duroc boar population","volume":"141","author":"Zhao","year":"2020","journal-title":"Theriogenology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"skab188","DOI":"10.1093\/jas\/skab188","article-title":"Identification of new semen trait-related candidate genes in Duroc boars through genome-wide association and weighted gene co-expression network analyses","volume":"99","author":"Mei","year":"2021","journal-title":"J. Anim. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Luo, H., Hu, L., Brito, L.F., Dou, J., Sammad, A., Chang, Y., Ma, L., Guo, G., Liu, L., and Zhai, L. (2022). Weighted single-step GWAS and RNA sequencing reveals key candidate genes associated with physiological indicators of heat stress in Holstein cattle. J. Anim. Sci. Biotechnol., 13.","DOI":"10.1186\/s40104-022-00748-6"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"550","DOI":"10.3168\/jds.2020-18766","article-title":"Major quantitative trait loci influencing milk production and conformation traits in Guernsey dairy cattle detected on Bos taurus autosome 19","volume":"104","author":"Li","year":"2021","journal-title":"J. Dairy. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Kim, S., Lim, B., Cho, J., Lee, S., Dang, C.G., Jeon, J.H., Kim, J.M., and Lee, J. (2021). Genome-wide identification of candidate genes for milk production traits in Korean Holstein cattle. Animals, 11.","DOI":"10.3390\/ani11051392"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1038\/s41588-022-01153-5","article-title":"A multi-tissue atlas of regulatory variants in cattle","volume":"54","author":"Liu","year":"2022","journal-title":"Nat. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","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":"ref_16","doi-asserted-by":"crossref","first-page":"4251","DOI":"10.2527\/jas2017.1683","article-title":"Genetic parameters for semen quality and quantity traits in five pig lines","volume":"95","author":"Marques","year":"2017","journal-title":"J. Anim. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4666","DOI":"10.2527\/jas.2016-0803","article-title":"Effects of feeding regimen on weight gain, semen characteristics, libido, and lameness in 170- to 250-kilogram Duroc boars","volume":"94","author":"Wang","year":"2016","journal-title":"J. Anim. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Covarrubias-Pazaran, G. (2016). Genome-Assisted Prediction of Quantitative Traits Using the R Package sommer. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0156744"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1086\/519795","article-title":"PLINK: A tool set for whole-genome association and population-based linkage analyses","volume":"81","author":"Purcell","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"ref_20","unstructured":"Madsen, P., Srensen, P., Su, G., Damgaard, L.H., and Labouriau, R.E. (2006, January 13\u201318). DMU\u2014A package for analyzing multivariate mixed models. Proceedings of the 8th World Congress on Genetics Applied to Livestock Production, Belo Horizonte, Brazil."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"16","DOI":"10.3168\/jds.2008-1514","article-title":"Invited review: Reliability of genomic predictions for North American Holstein bulls","volume":"92","author":"VanRaden","year":"2009","journal-title":"J. Dairy. Sci."},{"key":"ref_22","unstructured":"O\u2019Connell, J. (2017). MMAP: Mixed Model Analysis for Pedigrees and Populations, University of Matyland School of Medicine."},{"key":"ref_23","unstructured":"R Core Team (2013). R: A Language and Environment for Statistical Computing, Foundation for Statistical Computing."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1038\/ejhg.2011.39","article-title":"Genomic inflation factors under polygenic inheritance","volume":"19","author":"Yang","year":"2011","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_25","first-page":"100141","article-title":"clusterProfiler 4.0: A universal enrichment tool for interpreting omics data","volume":"2","author":"Wu","year":"2021","journal-title":"Innovation"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.anireprosci.2014.01.012","article-title":"Genome-wide association study for poor sperm motility in Holstein-Friesian bulls","volume":"146","author":"Hering","year":"2014","journal-title":"Anim. Reprod. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1111\/jbg.12393","article-title":"Estimation of genetic parameters and season effects for semen traits in three pig breeds of South China","volume":"136","author":"Li","year":"2019","journal-title":"J. Anim. Breed. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Wang, X., Wang, L., Shi, L., Zhang, P., Li, Y., Li, M., Tian, J., Wang, L., and Zhao, F. (2022). GWAS of Reproductive Traits in Large White Pigs on Chip and Imputed Whole-Genome Sequencing Data. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232113338"},{"key":"ref_29","unstructured":"Wu, C. (2015). Animals Genetics, Higher Education Press."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.ajhg.2015.05.004","article-title":"RSPH3 mutations cause primary ciliary dyskinesia with central-complex defects and a near absence of radial spokes","volume":"97","author":"Jeanson","year":"2015","journal-title":"Am. J. Hum. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3185","DOI":"10.1074\/mcp.M115.050005","article-title":"Aberrant expression of dynein light chain 1 (DYNLT1) is associated with human male factor infertility","volume":"14","author":"Indu","year":"2015","journal-title":"Mol. Cell Proteom."},{"key":"ref_32","first-page":"4128","article-title":"Proteomic analysis of mammalian sperm cells identifies new components of the centrosome","volume":"127","author":"Sante","year":"2014","journal-title":"J. Cell Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1016\/j.ajhg.2021.06.010","article-title":"Bi-allelic mutations of DNAH10 cause primary male infertility with asthenoteratozoospermia in humans and mice","volume":"108","author":"Tu","year":"2021","journal-title":"Am. J. Hum. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1093\/molehr\/gaz009","article-title":"Isoform-specific GSK3A activity is negatively correlated with human sperm motility","volume":"25","author":"Freitas","year":"2019","journal-title":"Mol. Hum. Reprod."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1095\/biolreprod.116.141408","article-title":"A nonsense mutation in Ccdc62 gene is responsible for spermiogenesis defects and male infertility in repro29\/repro29 mice","volume":"96","author":"Li","year":"2017","journal-title":"Biol. Reprod."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1093\/humrep\/dez246","article-title":"Exome sequencing reveals novel causes as well as new candidate genes for human globozoospermia","volume":"35","author":"Oud","year":"2020","journal-title":"Hum. Reprod."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1093\/biolre\/ioz071","article-title":"Intraflagellar transport protein 74 is essential for spermatogenesis and male fertility in micedagger","volume":"101","author":"Shi","year":"2019","journal-title":"Biol. Reprod."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"C1092","DOI":"10.1152\/ajpcell.00450.2019","article-title":"The essential role of intraflagellar transport protein IFT81 in male mice spermiogenesis and fertility","volume":"318","author":"Qu","year":"2020","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1006\/bbrc.2001.6048","article-title":"A novel spermatogenesis-related factor-1 gene expressed in maturing rat testis","volume":"289","author":"Yamano","year":"2001","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"E430","DOI":"10.1073\/pnas.1424648112","article-title":"Spata6 is required for normal assembly of the sperm connecting piece and tight head-tail conjunction","volume":"112","author":"Yuan","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1111\/andr.12742","article-title":"Increased DNA methylation in the spermatogenesis-associated (SPATA) genes correlates with infertility","volume":"8","author":"Sujit","year":"2020","journal-title":"Andrology"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Takemoto, N., Yoshimura, T., Miyazaki, S., Tashiro, F., and Miyazaki, J. (2016). Gtsf1l and Gtsf2 are specifically expressed in gonocytes and spermatids but are not essential for spermatogenesis. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0150390"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"14279","DOI":"10.1038\/ncomms14279","article-title":"X-linked primary ciliary dyskinesia due to mutations in the cytoplasmic axonemal dynein assembly factor PIH1D3","volume":"8","author":"Olcese","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1007\/s004390000427","article-title":"The human dynein intermediate chain 2 gene (DNAI2): Cloning, mapping, expression pattern, and evaluation as a candidate for primary ciliary dyskinesia","volume":"107","author":"Pennarun","year":"2000","journal-title":"Hum Genet."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/j.ajhg.2008.10.001","article-title":"DNAI2 mutations cause primary ciliary dyskinesia with defects in the outer dynein arm","volume":"83","author":"Loges","year":"2008","journal-title":"Am. J. Hum. Genet."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Al-Mutairi, D.A., Alsabah, B.H., Alkhaledi, B.A., Pennekamp, P., and Omran, H. (2022). Identification of a novel founder variant in DNAI2 cause primary ciliary dyskinesia in five consanguineous families derived from a single tribe descendant of Arabian Peninsula. Front. Genet., 13.","DOI":"10.3389\/fgene.2022.1017280"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1038\/cr.2017.100","article-title":"Mettl3-mediated m(6)A regulates spermatogonial differentiation and meiosis initiation","volume":"27","author":"Xu","year":"2017","journal-title":"Cell Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e44957","DOI":"10.15252\/embr.201744957","article-title":"PNLDC1, mouse pre-piRNA Trimmer, is required for meiotic and post-meiotic male germ cell development","volume":"19","author":"Nishimura","year":"2018","journal-title":"EMBO Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1038\/s41467-017-00854-4","article-title":"PNLDC1 is essential for piRNA 3\u2032 end trimming and transposon silencing during spermatogenesis in mice","volume":"8","author":"Ding","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1038\/cr.2017.125","article-title":"An essential role for PNLDC1 in piRNA 3\u2032 end trimming and male fertility in mice","volume":"27","author":"Zhang","year":"2017","journal-title":"Cell Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e45824","DOI":"10.15252\/embr.201845824","article-title":"Trimming it short: PNLDC1 is required for piRNA maturation during mouse spermatogenesis","volume":"19","author":"Bronkhorst","year":"2018","journal-title":"EMBO Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1007\/s10265-016-0895-z","article-title":"Novel insights into the molecular mechanism of sperm-egg fusion via IZUMO1","volume":"130","author":"Inoue","year":"2017","journal-title":"J. Plant Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1093\/biolre\/ioab048","article-title":"Sperm-oocyte signaling: The role of IZUMO1R and CD9 in PTK2B activation and actin remodeling at the sperm binding sitedagger","volume":"104","author":"Wang","year":"2021","journal-title":"Biol. Reprod."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1007\/s10815-017-1101-5","article-title":"Mutational analysis of IZUMO1R in women with fertilization failure and polyspermy after in vitro fertilization","volume":"35","author":"Yu","year":"2018","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1038\/s41431-020-00807-4","article-title":"Homozygous variants in PANX1 cause human oocyte death and female infertility","volume":"29","author":"Wang","year":"2021","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2465","DOI":"10.1210\/jcem.86.6.7539","article-title":"Absence of mutations involving the LIM homeobox domain gene LHX9 in 46,XY gonadal agenesis and dysgenesis","volume":"86","author":"Ottolenghi","year":"2001","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1159\/000518323","article-title":"LIM Homeodomain (LIM-HD) genes and their co-regulators in developing reproductive system and disorders of sex development","volume":"16","author":"Singh","year":"2021","journal-title":"Sex. Dev."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1002\/humu.23664","article-title":"In vitro functional characterization of the novel DHH mutations p.(Asn337Lysfs*24) and p.(Glu212Lys) associated with gonadal dysgenesis","volume":"39","author":"Tajouri","year":"2018","journal-title":"Hum. Mutat."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1007\/s00439-020-02189-5","article-title":"DHH pathogenic variants involved in 46,XY disorders of sex development differentially impact protein self-cleavage and structural conformation","volume":"139","author":"Elzaiat","year":"2020","journal-title":"Hum. Genet."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1007\/s10815-021-02140-1","article-title":"Mutations in the desert hedgehog (DHH) gene in the disorders of sexual differentiation and male infertility","volume":"38","author":"Mehta","year":"2021","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1091\/mbc.E17-08-0510","article-title":"DRC2\/CCDC65 is a central hub for assembly of the nexin-dynein regulatory complex and other regulators of ciliary and flagellar motility","volume":"29","author":"Bower","year":"2018","journal-title":"Mol. Biol. Cell"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Horani, A., Brody, S.L., Ferkol, T.W., Shoseyov, D., Wasserman, M.G., Ta-shma, A., Wilson, K.S., Bayly, P.V., Amirav, I., and Cohen-Cymberknoh, M. (2013). CCDC65 mutation causes primary ciliary dyskinesia with normal ultrastructure and hyperkinetic cilia. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0072299"}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/15\/3\/438\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:27:00Z","timestamp":1760027220000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/15\/3\/438"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,5]]},"references-count":62,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["ani15030438"],"URL":"https:\/\/doi.org\/10.3390\/ani15030438","relation":{},"ISSN":["2076-2615"],"issn-type":[{"value":"2076-2615","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,5]]}}}