Simple item page
 

A massive alteration of gene expression in undescended testicles of dogs and the association of KAT6A variants with cryptorchidism

cris.virtual.author-orcid0000-0002-1041-3576
cris.virtual.author-orcid0000-0002-1806-0891
cris.virtual.author-orcid0000-0001-9465-3851
cris.virtual.author-orcid#PLACEHOLDER_PARENT_METADATA_VALUE#
cris.virtual.author-orcid#PLACEHOLDER_PARENT_METADATA_VALUE#
cris.virtual.author-orcid#PLACEHOLDER_PARENT_METADATA_VALUE#
cris.virtual.author-orcid#PLACEHOLDER_PARENT_METADATA_VALUE#
cris.virtual.author-orcid#PLACEHOLDER_PARENT_METADATA_VALUE#
cris.virtualsource.author-orcidb1f9951f-b018-4795-8cff-c7188dd69448
cris.virtualsource.author-orcid6a2f8857-003b-41ec-9112-0ef6941bfd06
cris.virtualsource.author-orcida96d2343-ee65-450d-8ce2-355a51255d10
cris.virtualsource.author-orcid#PLACEHOLDER_PARENT_METADATA_VALUE#
cris.virtualsource.author-orcid9fd4d04e-0912-425f-812f-aab2e3debe36
cris.virtualsource.author-orcid#PLACEHOLDER_PARENT_METADATA_VALUE#
cris.virtualsource.author-orcid5b5c83e3-837f-42d1-855b-f39952dd433b
cris.virtualsource.author-orcid#PLACEHOLDER_PARENT_METADATA_VALUE#
dc.abstract.enCryptorchidism 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 = 122) and control (n = 173) dogs showed that the TT genotype (rs850666472, p.Ala1230Val) and the AA genotype in 3′UTR (16:23716202G>A) in KATA6, responsible for acetylation of lysine 9 in histone H3, are associated with cryptorchidism (P = 0.0383). Both the transcript level of KAT6A and H3K9 acetylation were lower in undescended testes, and additionally, the acetylation depended on the genotypes in exon 17 and the 3′UTR. 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 KAT6A can be considered markers associated with the risk of this disorder.
dc.affiliationWydział Medycyny Weterynaryjnej i Nauk o Zwierzętach
dc.affiliationWydział Rolnictwa, Ogrodnictwa i Biotechnologii
dc.affiliation.instituteKatedra Genetyki i Podstaw Hodowli Zwierząt​​
dc.affiliation.instituteKatedra Metod Matematycznych i Statystycznych
dc.contributor.authorStachowiak, Monika
dc.contributor.authorNowacka-Woszuk, Joanna
dc.contributor.authorSzabelska-Beręsewicz, Alicja
dc.contributor.authorZyprych-Walczak, Joanna Grażyna
dc.contributor.authorKrzeminska, Paulina
dc.contributor.authorSosinski, Oskar
dc.contributor.authorNowak, Tomasz
dc.contributor.authorŚwitoński, Marek
dc.date.accessioned2024-11-29T07:39:58Z
dc.date.available2024-11-29T07:39:58Z
dc.date.issued2024
dc.description.abstract<jats:p> 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 ( <jats:italic>n</jats:italic> = 122) and control ( <jats:italic>n</jats:italic> = 173) dogs showed that the TT genotype (rs850666472, p.Ala1230Val) and the AA genotype in 3′UTR (16:23716202G&gt;A) in <jats:italic>KATA6</jats:italic> , responsible for acetylation of lysine 9 in histone H3, are associated with cryptorchidism ( <jats:italic>P</jats:italic> = 0.0383). Both the transcript level of <jats:italic>KAT6A</jats:italic> and H3K9 acetylation were lower in undescended testes, and additionally, the acetylation depended on the genotypes in exon 17 and the 3′UTR. 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 <jats:italic>KAT6A</jats:italic> can be considered markers associated with the risk of this disorder. </jats:p>
dc.description.bibliographyil., bibliogr.
dc.description.financepublication_act
dc.description.financecost13408,57
dc.description.if9,4
dc.description.number7
dc.description.points200
dc.description.volume121
dc.identifier.doi10.1073/pnas.2312724121
dc.identifier.eissn1091-6490
dc.identifier.issn0027-8424
dc.identifier.urihttps://sciencerep.up.poznan.pl/handle/item/2138
dc.languageen
dc.pbn.affiliationanimal science and fisheries
dc.pbn.affiliationveterinary science
dc.pbn.affiliationbiological sciences
dc.pbn.affiliationbiotechnology
dc.pbn.affiliationagriculture and horticulture
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of America
dc.relation.pagese2312724121
dc.rightsOther
dc.sciencecloudsend
dc.share.typeOTHER
dc.subject.encryptorchidism
dc.subject.enDNA methylation
dc.subject.enhistone H3 acetylation
dc.subject.enRNA-seq
dc.subject.entranscriptome
dc.titleA massive alteration of gene expression in undescended testicles of dogs and the association of KAT6A variants with cryptorchidism
dc.typeJournalArticle
dspace.entity.typePublication
oaire.citation.issue7
oaire.citation.volume121
project.funder.nameResearch financed from The work was supported by the National Science Centre research Grant No. 2018/29/B/NZ9/01065. OA fee from PREIDUB Project PULS