{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:27:08Z","timestamp":1791289628379,"version":"4.3.0"},"reference-count":51,"publisher":"National Academy of Sciences","issue":"7","license":[{"start":{"date-parts":[[2024,2,5]],"date-time":"2024-02-05T00:00:00Z","timestamp":1707091200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"National Science Centre in Poland","award":["2018\/29\/B\/NZ9\/01065"],"award-info":[{"award-number":["2018\/29\/B\/NZ9\/01065"]}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,2,13]]},"abstract":"<jats:p>\n                    Cryptorchidism is the most common form of disorder of sex development in male dogs, but its hereditary predisposition is poorly elucidated. The gonadal transcriptome of nine unilaterally cryptorchid dogs and seven control dogs was analyzed using RNA-seq. Comparison between the scrotal and inguinal gonads of unilateral cryptorchid dogs revealed 8,028 differentially expressed genes (DEGs) (3,377 up-regulated and 4,651 down-regulated). A similar number of DEGs (7,619) was found by comparing the undescended testicles with the descended testicles of the control dogs. The methylation status of the selected DEGs was also analyzed, with three out of nine studied DEGs showing altered patterns. Bioinformatic analysis of the cDNA sequences revealed 20,366 SNP variants, six of which showed significant differences in allelic counts between cryptorchid and control dogs. Validation studies in larger cohorts of cryptorchid (\n                    <jats:italic>n<\/jats:italic>\n                    = 122) and control (\n                    <jats:italic>n<\/jats:italic>\n                    = 173) dogs showed that the TT genotype (rs850666472, p.Ala1230Val) and the AA genotype in 3\u2032UTR (16:23716202G&gt;A) in\n                    <jats:italic>KATA6<\/jats:italic>\n                    , responsible for acetylation of lysine 9 in histone H3, are associated with cryptorchidism (\n                    <jats:italic>P<\/jats:italic>\n                    = 0.0383). Both the transcript level of\n                    <jats:italic>KAT6A<\/jats:italic>\n                    and H3K9 acetylation were lower in undescended testes, and additionally, the acetylation depended on the genotypes in exon 17 and the 3\u2032UTR. Our study showed that the massive alteration of the transcriptome in undescended testicles is not caused by germinal DNA variants in DEG regulatory sequences but is partly associated with an aberrant DNA methylation and H3K9 acetylation patterns. Moreover, variants of\n                    <jats:italic>KAT6A<\/jats:italic>\n                    can be considered markers associated with the risk of this disorder.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2312724121","type":"journal-article","created":{"date-parts":[[2024,2,5]],"date-time":"2024-02-05T15:09:16Z","timestamp":1707145756000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":14,"title":["A massive alteration of gene expression in undescended testicles of dogs and the association of\n                    <i>KAT6A<\/i>\n                    variants with cryptorchidism"],"prefix":"10.1073","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3485-1359","authenticated-orcid":false,"given":"Monika","family":"Stachowiak","sequence":"first","affiliation":[{"name":"Department of Genetics and Animal Breeding, Poznan University of Life Sciences, 60-637 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1041-3576","authenticated-orcid":false,"given":"Joanna","family":"Nowacka-Woszuk","sequence":"additional","affiliation":[{"name":"Department of Genetics and Animal Breeding, Poznan University of Life Sciences, 60-637 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1806-0891","authenticated-orcid":false,"given":"Alicja","family":"Szabelska-Beresewicz","sequence":"additional","affiliation":[{"name":"Department of Mathematical and Statistical Methods, Poznan University of Life Sciences, 60-637 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9465-3851","authenticated-orcid":false,"given":"Joanna","family":"Zyprych-Walczak","sequence":"additional","affiliation":[{"name":"Department of Mathematical and Statistical Methods, Poznan University of Life Sciences, 60-637 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4532-6974","authenticated-orcid":false,"given":"Paulina","family":"Krzeminska","sequence":"additional","affiliation":[{"name":"Department of Genetics and Animal Breeding, Poznan University of Life Sciences, 60-637 Poznan, Poland"},{"name":"Department of Ribonucleoprotein Biochemistry, Institute of Bioorganic Chemistry Polish Academy of Sciences, 61-704 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3156-6428","authenticated-orcid":false,"given":"Oskar","family":"Sosinski","sequence":"additional","affiliation":[{"name":"Department of Genetics and Animal Breeding, Poznan University of Life Sciences, 60-637 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1820-5202","authenticated-orcid":false,"given":"Tomasz","family":"Nowak","sequence":"additional","affiliation":[{"name":"Department of Genetics and Animal Breeding, Poznan University of Life Sciences, 60-637 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2539-9508","authenticated-orcid":false,"given":"Marek","family":"Switonski","sequence":"additional","affiliation":[{"name":"Department of Genetics and Animal Breeding, Poznan University of Life Sciences, 60-637 Poznan, 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