Animal genetics最新文献

{"title":"A Nelore Cattle Structural Variant Catalog.","authors":"Thales de Lima Silva, Alexander S Leonard, Pablo Augusto de Souza Fonseca, Haroldo Henrique de R Neves, Alexandre M Ruiz, Lucas Tassoni Andrietta, Gerardo A Fernandes Júnior, Júlio Cesar de C Balieiro, Hubert Pausch, Roberto Carvalheiro, Ricardo Vieira Ventura","doi":"10.1002/age.70225","DOIUrl":"10.1002/age.70225","url":null,"abstract":"<p><p>Structural variants (SVs) contribute more nucleotide divergence between mammalian genomes than single nucleotide polymorphisms, yet no population-scale, long-read-validated SV catalog has been available for Bos indicus cattle. Nelore, the most numerically important indicine breed worldwide, diverges substantially from the taurine-derived reference genome used for most bovine SV discovery, leaving its structural variation largely uncharacterized. Long-read sequencing of 20 Nelore bulls with two complementary callers (Sniffles2, SVIM) yielded 82 581 dual-caller concordant SVs, of which 74 222 insertions and deletions passed independent read-based validation. Ensembl VEP annotation identified 561 HIGH-impact variants (0.75% of the catalog) across 7040 protein-coding genes. Only 22 894 SVs (30.7%), including 147 of 561 HIGH-impact variants (26.2%), could be tagged by an existing BovineHD SNP (r² ≥ 0.8), showing that routine array genotyping captures a minority of this variation. Intersection with an indicine-ancestry SNP map identified 6114 SVs (8.2%) enriched in Bos indicus, including 61 HIGH-impact variants overlapping genes with plausible roles in immune/inflammatory defense and oxidative-stress response, providing a resource and candidate variant set for genomic selection and tropical-adaptation studies in indicine cattle.</p>","PeriodicalId":7905,"journal":{"name":"Animal genetics","volume":"57 5","pages":"e70225"},"PeriodicalIF":2.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13677160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149219867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to \"MiR-376c-3p Targets STRBP mRNA to Regulate Cashmere Goat Hair Follicle Stem Cell Proliferation and Multipotency by Inhibiting the Wnt/β-catenin and BMP Signalling Pathways\".","authors":"","doi":"10.1002/age.70222","DOIUrl":"https://doi.org/10.1002/age.70222","url":null,"abstract":"","PeriodicalId":7905,"journal":{"name":"Animal genetics","volume":"57 5","pages":"e70222"},"PeriodicalIF":2.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149219895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond the Transcriptome: The m⁶A Epitranscriptome in Bovine Mastitis.","authors":"Shraddha Dwivedi, Amit Kumar, Diksha Upreti, Ayushi Singh","doi":"10.1002/age.70223","DOIUrl":"https://doi.org/10.1002/age.70223","url":null,"abstract":"<p><p>Bovine mastitis is a heterogeneous inflammatory disease that compromises milk production, animal welfare and dairy sustainability. Despite extensive transcriptomic and epigenomic research, a PubMed search completed in September 2026 identified only 12 primary studies addressing epitranscriptomic regulation in bovine mastitis, representing approximately 0.1% of indexed publications. This review critically evaluates N⁶-methyladenosine (m⁶A), the most extensively studied RNA modification in bovine mastitis, its regulatory machinery and effects on mammary immunity, while identifying m⁵C and A-to-I editing as priorities for mechanistic investigation. Current evidence identifies transcript-specific RNA stability as the best-supported mechanism and provides a foundation for investigating m⁶A-dependent translation. Functional studies of ALKBH5-LOC4191, YTHDF2-IER3, YTHDF2-associated CCL20 and CCL5 regulation, m⁶A-regulated LncRNA7825 and FTO-FN1 demonstrate that m⁶A reshapes inflammatory signalling, mitochondrial stress, epithelial-barrier integrity, cell survival and bacterial control. Synthesizing these findings, we propose a context-dependent RNA-fate checkpoint model in which biological effects depend on the modified transcript, effector protein, pathogen, cellular context and infection phase. The FTO-FN1 axis shows that bacterial control and tissue protection can diverge, establishing them as complementary outcomes. Future studies should test whether m⁶A provides an early post-transcriptional response layer and whether pathogens manipulate it, using time-resolved multi-omics, nucleotide-specific perturbation, primary cells, mammary organoids and longitudinal cattle samples. Parallel profiling of non-m⁶A modifications should define interacting regulatory layers. These approaches should establish causal modification sites, resolve pathogen-specific regulation, connect molecular mechanisms with disease trajectories, and support validated milk-based biomarkers, mammary-targeted interventions and prioritization of stable genetic variants for breeding mastitis-resistant cattle.</p>","PeriodicalId":7905,"journal":{"name":"Animal genetics","volume":"57 5","pages":"e70223"},"PeriodicalIF":2.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Additional PAX3 Variants for Dominant Blue Eyes in Cats","authors":"Marie Abitbol,&nbsp;Tess Eiselé,&nbsp;Elizaveta Lipovenko","doi":"10.1002/age.70199","DOIUrl":"https://doi.org/10.1002/age.70199","url":null,"abstract":"<p>Since the recent publication of the first feline variant of the <i>PAX3</i> (<i>Paired Box 3</i>) gene associated with blue eyes and minimal white spotting (DBE, Dominant Blue Eyes), three further variants of <i>PAX3</i> have been reported in felines. However, these four variants do not account for all the different feline lines that exhibit DBE. Whole-genome sequencing using short-read and long-read technologies identified a large complex structural variant involving two deletions and an inversion in a purebred line of British shorthair and longhair cats. All 39 British cats with a BDE phenotype were heterozygous for the variant, that was absent in 47 non-DBE cats and 16 DBE cats from other breeding lines. The purebred British shorthair founder female named Nadeya was also heterozygous for the variant, and the segregation of the variant is consistent with dominant inheritance. We named this NC_058375.1:g.[205097674_207411974del;207411975_211290497inv;211290498_211387174del] variant the <i>DBE</i>^<i>NAD</i> (<i>Nadeya Dominant Blue Eyes</i>) allele. In addition, a candidate gene approach identified a nonsense variant, XM_019838731.3:c.784C&gt;T, in the fifth exon of <i>PAX3</i> in a second breeding line originating from a female named Marusya. The segregation of this nonsense variant is consistent with dominant inheritance, and a perfect genotype–phenotype correlation was observed in the 16 cats from this line, so we propose that this sixth variant of <i>PAX3</i> represents the <i>DBE</i>^<i>MARU</i> (<i>Marusya Dominant Blue Eyes</i>) allele in the domestic cat. Our study has identified two further variants of the <i>PAX3</i> gene associated with DBE in domestic cats, which will help to improve genotyping of the breeding stock.</p>","PeriodicalId":7905,"journal":{"name":"Animal genetics","volume":"57 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/age.70199","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148943083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-Wide Association Analysis of Hippocampal Neuroplasticity as an Indicator of Stress Responsiveness in Laying Hens (Gallus gallus domesticus)","authors":"Lindsay Neuert,&nbsp;Vern Osborne,&nbsp;Elena A. Armstrong,&nbsp;Fábio Pértille,&nbsp;Carlos Guerrero Bosagna,&nbsp;Timothy Boswell,&nbsp;Tom V. Smulders,&nbsp;Christine F. Baes,&nbsp;Bayode O. Makanjuola","doi":"10.1002/age.70202","DOIUrl":"10.1002/age.70202","url":null,"abstract":"<p>Environmental stressors in commercial poultry systems can negatively affect bird welfare, although individuals vary considerably in their responses. Neuroplasticity within the hippocampus, measured through the density of doublecortin-positive (DCX⁺) neurons, provides a potential biomarker of stress experience in laying hens. However, the genetic basis underlying variation in this biomarker remains poorly understood. A total of 42 H&amp;N and Hy-Line Brown hens housed in a multitier free range and enriched cage system, respectively, were genotyped using Genotyping by Sequencing, yielding over 200 000 SNP markers after initial filtering. Hippocampal tissue sections were immunostained for DCX to quantify the density of highly plastic neurons. A genome-wide association analysis identified 19 genomic regions across eight chromosomes within the top 1% of windows explaining the greatest proportion of genetic variance in the neuroplasticity phenotype. Within ±100 kb of these regions, 39 annotated genes were identified, several of which are involved in cellular regulation and genetic information processing pathways. Notably, <i>PIK3R6</i>, <i>VPS37D</i>, <i>STX1A</i>, <i>BAZ1B</i>, <i>HGH1</i>, <i>MAF1</i>, <i>MAPK15</i>, and <i>PIT54</i> emerged as positional candidate genes potentially contributing to variation in stress responsiveness. These findings provide preliminary insight into the genetic architecture of hippocampal neuroplasticity in laying hens and highlight candidate genes that may contribute to individual differences in stress response, with potential implications for breeding strategies aimed at improving poultry welfare.</p>","PeriodicalId":7905,"journal":{"name":"Animal genetics","volume":"57 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/age.70202","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148918040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estimation Model of Pig Weight Based on Body Measurements and Analysis of Its Genetic Basis","authors":"Yanfeng Fu,&nbsp;Chao Liao,&nbsp;Weining Li,&nbsp;Chaohui Dai,&nbsp;Xuemin Wang,&nbsp;Hui Li,&nbsp;Jin Hu,&nbsp;Jinhua Cheng","doi":"10.1002/age.70194","DOIUrl":"10.1002/age.70194","url":null,"abstract":"<div>\u0000 \u0000 <p>Body weight and body measurements are key indicators of growth and economic efficiency in pigs, but conventional weighing is labor-intensive and stressful, increasing disease risk and necessitating non-contact estimation. We measured five dimensions (body length, chest circumference, abdominal circumference, body width, and body height) in 811 Suzi black pigs and constructed six multiple linear regression models using different combinations. All models had <i>R</i>² &gt; 0.91, with adjusted <i>R</i>² also exceeding 0.91, and the model combining length, chest, and abdominal circumference gave the lowest RMSE, balancing accuracy and practicality. Separately, we performed GWAS on 165 genotyped individuals (100 K SNP chip and GBS) for age (as a growth rate proxy), body weight, and the five measurements. No SNP reached genome-wide significance (<i>p</i> &lt; 1.86 × 10⁻⁶), but three suggestive loci (<i>p</i> &lt; 1.39 × 10⁻⁵) were detected: SNP 4_12 319 200 for age (35.55% variance), a pleiotropic SNP 1_60 912 826 associated with length, chest, and abdominal circumference (42.10%, 53.06%, and 45.97% variance), and SNP 1_60 638 159 for abdominal circumference. Positional mapping identified <i>EPHA7</i> as the nearest candidate gene. Enrichment analyses revealed focal adhesion, receptor tyrosine kinase, IgSF-CAM, integrin, and PI3K-Akt pathways, with <i>EPHA7</i> and <i>FYN</i> as key regulators. Notably, the three traits in the best model mapped to the same pleiotropic locus, suggesting a shared genetic basis. This study provides a practical estimation tool and suggestive markers, supporting non-contact weighing systems and molecular breeding.</p>\u0000 </div>","PeriodicalId":7905,"journal":{"name":"Animal genetics","volume":"57 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148910839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Large-Scale Cross-Population Evaluation of Genetic Risk Variants for Dilated Cardiomyopathy in Dobermanns","authors":"Alma H. Hulsman,&nbsp;Gwen Flokstra,&nbsp;Christina Kijan,&nbsp;Marilijn van Rumpt,&nbsp;Johannes C. M. Vernooij,&nbsp;Thomas C. Nelson,&nbsp;Sophie Liu,&nbsp;Lieke Vree,&nbsp;Magdalena Harakalova,&nbsp;Ingrid Ljungvall,&nbsp;Jens Haggstrom,&nbsp;Gerhard Wess,&nbsp;Hille Fieten,&nbsp;Marjo K. Hytönen,&nbsp;Hannes Lohi,&nbsp;Frank G. van Steenbeek","doi":"10.1002/age.70206","DOIUrl":"10.1002/age.70206","url":null,"abstract":"<p>Previous studies suggest that genetic risk factors for dilated cardiomyopathy (DCM) in Dobermann dogs may differ between populations, complicating the use of genetic tests across subpopulations. Variants in pyruvate dehydrogenase kinase 4 (<i>PDK4</i>) and titin (<i>TTN</i>) have been associated with DCM in North American Dobermanns, whereas two loci on chromosome 5 involving Protein Kinase AMP-Activated Catalytic Subunit Alpha 2 (<i>PRKAA2</i>) and Ring Finger Protein 207 (<i>RNF207</i>) have been implicated in European populations. To assess the consistency of these signals across populations of Dobermanns, we harmonized and imputed genotype data from a Discovery cohort (<i>n</i> = 444) and a Replication cohort (<i>n</i> = 1771), and supplemented these with allele frequency data from a large diversity cohort (<i>n</i> = 3226) for cross-platform analyses. We detected a shared association signal near <i>RNF207</i> in affected dogs in both Europe and North America. In contrast, SNPs located in and near <i>PDK4</i> and <i>TTN</i> variants showed no association with DCM in either population. These findings indicate that the <i>RNF207</i> variant represents a shared genetic risk factor for DCM in Dobermanns across populations, and support the dog, particularly the Dobermann, as a relevant spontaneous model for RNF207-driven DCM. The previously reported associations between <i>PDK4</i> and <i>TTN</i> variants and DCM were not replicated in the North American Dobermann population, nor in the European Dobermann populations. Also, these results highlight the need for population-specific validation and functional validation of identified variants where possible, before implementation of variants in genetic testing strategies.</p>","PeriodicalId":7905,"journal":{"name":"Animal genetics","volume":"57 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/age.70206","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148918029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive Analysis of miRNAs and Predicted Protein Interaction Networks in Skeletal Muscle Development of Myostatin-Deficient Rabbits","authors":"Zhi-Xian Song,&nbsp;Paing Oo Kyaw,&nbsp;Muhammad Farhab,&nbsp;Ting Zhang,&nbsp;Jingyan Liang,&nbsp;Yu-Guo Yuan","doi":"10.1002/age.70193","DOIUrl":"10.1002/age.70193","url":null,"abstract":"<div>\u0000 \u0000 <p>Myostatin (MSTN), encoded by the <i>MSTN</i> gene, is a critical negative regulator of skeletal muscle mass. This study aims to identify and characterize the miRNAs involved in the development of the double-muscling phenotype in <i>MSTN</i>-deficient rabbits. We performed high-throughput sequencing to analyze the miRNA expression profiles in gluteus maximus tissue from wild type (<i>MSTN</i>^+/+) and <i>MSTN</i>-KO (<i>MSTN</i>^+/− and <i>MSTN</i>^−/− inclusive) rabbits. Differentially expressed miRNAs (DEmiRNAs) were identified, and their potential target genes were predicted. Functional enrichment analysis of these target mRNAs was conducted using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database to elucidate the involved biological pathways and regulatory networks. A total of 25 DEmiRNAs (13 downregulated and 12 upregulated, |log₂FC| ≥ 1.0, adjusted <i>p</i> &lt; 0.05) and 1178 differentially expressed mRNAs (408 upregulated and 770 downregulated, |log₂FC| ≥ 2.0, adjusted <i>p</i> &lt; 0.05) were identified in <i>MSTN</i>-KO compared to <i>MSTN</i>^+/+ rabbits. Bioinformatics analysis revealed that the target genes of these DEmiRNAs were significantly enriched in key pathways governing muscle growth and metabolism, including the PI3K-Akt signaling pathway, MAPK signaling pathway, and pathways related to ECM-receptor interaction and insulin signaling. Notably, many predicted target mRNAs are expressed by genes that encode key inhibitors of myogenesis (e.g., <i>HDAC4</i>) and major extracellular matrix components (e.g., <i>COL4A3, POSTN</i>). Our results demonstrate that <i>MSTN</i> deficiency induces a distinct and widespread change in the miRNA expression landscape of skeletal muscle.</p>\u0000 </div>","PeriodicalId":7905,"journal":{"name":"Animal genetics","volume":"57 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148904917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying Co-Expressed lncRNAs Correlated With Traits of Interest in an Animal Model for Metabolic Diseases in Humans","authors":"Lucas Echevarria Nascimento,&nbsp;Bruna Pereira Martins da Silva,&nbsp;Camila Sabino de Oliveira,&nbsp;Mariah Castro Durval,&nbsp;Felipe André Oliveira Freitas,&nbsp;Fernanda Nery Ciconello,&nbsp;Izally Carvalho Gervásio,&nbsp;Simara Larissa Fanalli,&nbsp;Pablo Augusto de Souza Fonseca,&nbsp;Beatriz Gutiérrez-Gil,&nbsp;Vivian Vezzoni de Almeida,&nbsp;Aline Silva Mello Cesar","doi":"10.1002/age.70201","DOIUrl":"10.1002/age.70201","url":null,"abstract":"<p>Nutrigenomics investigates how nutrients modulate gene expression. Among them, fatty acids (FA) play important roles in regulating gene transcription, while long non-coding RNAs (lncRNAs) may be associated with gene regulation and metabolic diseases. This study aimed to analyze the hepatic transcriptome of pigs, a species frequently used as a model for nutrigenomic studies, to identify novel lncRNAs and their potential target genes in response to diets containing different sources of FA. Seventy-two pigs were fed four diets supplemented with 1.5% soybean oil (control), 3% canola oil, 3% fish oil, and 3% soybean oil. RNA sequencing of liver samples was performed to identify novel lncRNAs. Weighted Gene Co-expression Network Analysis (WGCNA) was used to identify modules associated with phenotypic traits related to lipid metabolism and inflammation. Functional enrichment analyses were then conducted to annotate genes within these modules using Gene Ontology (GO) terms and to assess overlap with Quantitative Trait Loci (QTL). The results revealed 106 novel lncRNAs potentially regulating genes associated with lipid metabolism and immune responses in pigs fed diets with different FA sources. These findings enhance understanding of the regulatory role of lncRNAs in pigs and reinforce their relevance as models for human metabolic diseases.</p>","PeriodicalId":7905,"journal":{"name":"Animal genetics","volume":"57 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13551055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148904991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Combination of Alleles in LMOD2 and a lncRNA is Strongly Associated With Myxomatous Mitral Valve Disease in Cavalier King Charles Spaniels","authors":"Lisbeth Høier Olsen,&nbsp;Arney Eva Gunnlaugsdóttir,&nbsp;Majbritt Busk Madsen,&nbsp;Isabella Jane Larsen,&nbsp;Maria Josefine Ubbe Reimann,&nbsp;Foteini Papadaki,&nbsp;Ingrid Ljungvall,&nbsp;Jens Häggström,&nbsp;Torben Martinussen,&nbsp;Henrik Duelund Pedersen,&nbsp;Torkel Falk,&nbsp;Merete Fredholm,&nbsp;Peter Karlskov-Mortensen","doi":"10.1002/age.70200","DOIUrl":"10.1002/age.70200","url":null,"abstract":"<p>A previous genome-wide association study identified regions on canine chromosome (cfa) 13 and 14 associated with early onset myxomatous mitral valve disease (MMVD) in Cavalier King Charles Spaniels (CKCS). In the present study, whole genome sequencing (WGS) of 9 CKCS cases (mitral regurgitation (MR) before 4.5 years or congestive heart failure (CHF) at any age due to MMVD) and 10 CKCS controls (no or mild MR after 8 years of age) identified &gt; 2000 genetic variants in the MMVD associated cfa13 and cfa14 regions. Ensembl Variant Effect Predictor (VEP) identified a possible functional impact of 18 variants. These were genotyped in 250 CKCS; 117 cases and 133 controls. The most significantly associated variants were a splice-site variant in a long noncoding RNA (lncRNA) on cfa13, a nonsynonymous variant in <i>HYAL4</i>, a 39 base-pair insertion in <i>LMOD2</i> and a synonymous variant in ENSCAFG00000024436 (<i>p</i>-values from 2.03E-08 to 4.20E-06). Concomitant homozygosity for risk alleles in <i>LMOD2</i> and the lncRNA gave an odds-ratio for MMVD of 52.5 compared to homozygosity for the nonrisk alleles (<i>p</i> = 0.00034, 95% CI: 8.8–1023.8). Upon validation of our results in an independent cohort, this gene variant combination in CKCS is expected to enable targeted breeding programs to reduce MMVD prevalence in CKCS.</p>","PeriodicalId":7905,"journal":{"name":"Animal genetics","volume":"57 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13552192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148904944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}