Identification of SNP markers for canine mammary gland tumours in females based on a genome-wide association study – preliminary results

Abstract Introduction The development of genetic research over recent decades has enabled the discovery of new genetic markers, such as single nucleotide polymorphisms (SNPs). This, as well as the full sequencing of the dog genome, has enabled genome-wide association studies (GWAS) to be used in the search for genetic causes of canine mammary tumours (CMTs). Material and Methods Genotypic data containing 175,000 SNPs, which had been obtained using the Illumina CanineHD BeadChip microarray technique, were available for analysis in this study. The data concerned 118 bitches, including 36 animals with CMT, representing various breeds and age groups. Statistical analysis was performed in two steps: quality control of genotyping data and genome-wide association analysis based on dominant, recessive, overdominant, codominant, and log-additive models with the single SNP effects. Results A total of 40 different SNPs significantly associated with CMT appearance were detected. Moreover, twelve SNPs showed statistical significance in more than one model. Of all the significant SNPs, two, namely BICF2G630136001 in the overdominant model and TIGRP2P107898_rs9044787 in the log-additive model, reached the 5−8 significance level. The other SNPs were significant to a 1−5 level. Conclusion In the group of SNPs indicated as significant in the GWAS analysis, several transpired to be localised within genes that may play an important role in CMT.

[1]  P. Vivas-Mejia,et al.  Increased Expression of the RBPMS Splice Variants Inhibits Cell Proliferation in Ovarian Cancer Cells , 2022, International journal of molecular sciences.

[2]  Xueqin Ran,et al.  Whole-genome sequence analysis reveals selection signatures for important economic traits in Xiang pigs , 2022, Scientific Reports.

[3]  M. Gallegos-Arreola,et al.  ESR2 gene variants (rs1256049, rs4986938, and rs1256030) and their association with breast cancer risk , 2022, PeerJ.

[4]  S. Sleijfer,et al.  The prognostic and predictive value of ESR1 fusion gene transcripts in primary breast cancer , 2021, BMC cancer.

[5]  Wei Zhang,et al.  ARHGEF19 promotes the growth of breast cancer in vitro and in vivo by the MAPK pathway. , 2021, Physiology International.

[6]  F. A. Rivera-Páez,et al.  Detection of single nucleotide polymorphisms (SNPs) in HER2, MUC1, ESR1, and BRCA1 genes associated with canine mammary cancer , 2021 .

[7]  L. Giudice,et al.  Genetic risk factors for endometriosis near estrogen receptor 1 and co-expression of genes in this region in endometrium. , 2021, Molecular human reproduction.

[8]  Luke H. Hoeppner,et al.  ASCL1-regulated DARPP-32 and t-DARPP stimulate small cell lung cancer growth and neuroendocrine tumour cell proliferation , 2020, British Journal of Cancer.

[9]  A. Boyko,et al.  A genome-wide association study of deafness in three canine breeds , 2020, PloS one.

[10]  Xian-jie Zeng,et al.  microRNA‐599 promotes apoptosis and represses proliferation and epithelial‐mesenchymal transition of papillary thyroid carcinoma cells via downregulation of Hey2‐depentent Notch signaling pathway , 2020, Journal of cellular physiology.

[11]  Ming Yan,et al.  The zinc-finger protein ZCCHC2 suppresses retinoblastoma tumorigenesis by inhibiting HectH9-mediated K63-linked polyubiquitination and activation of c-Myc. , 2020, Biochemical and biophysical research communications.

[12]  R. Medeiros,et al.  Estrogen receptors genotypes and canine mammary neoplasia , 2019, BMC Veterinary Research.

[13]  F. Feng,et al.  SNP mutation‐related genes in breast cancer for monitoring and prognosis of patients: A study based on the TCGA database , 2019, Cancer medicine.

[14]  R. Medeiros,et al.  Canine mammary tumor risk is associated with polymorphisms in RAD51 and STK11 genes , 2018, Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc.

[15]  Andries T Marees,et al.  A tutorial on conducting genome‐wide association studies: Quality control and statistical analysis , 2018, International journal of methods in psychiatric research.

[16]  A. Risvanli,et al.  Somatic SNPs of the BRCA2 gene at the fragments encoding RAD51 binding sites of canine mammary tumors , 2017, Veterinary and comparative oncology.

[17]  Bai-lian Li,et al.  Coexpression Network Analysis of Benign and Malignant Phenotypes of SIV-Infected Sooty Mangabey and Rhesus Macaque , 2016, PloS one.

[18]  K. Lindblad-Toh,et al.  Genome-Wide Analysis Identifies Germ-Line Risk Factors Associated with Canine Mammary Tumours , 2016, PLoS genetics.

[19]  Lei Liu,et al.  Potential diagnostic and prognostic marker dimethylglycine dehydrogenase (DMGDH) suppresses hepatocellular carcinoma metastasis in vitro and in vivo , 2016, Oncotarget.

[20]  J. Sur,et al.  Obesity, expression of adipocytokines, and macrophage infiltration in canine mammary tumors. , 2015, Veterinary journal.

[21]  K. Lindblad-Toh,et al.  Genome-wide analyses implicate 33 loci in heritable dog osteosarcoma, including regulatory variants near CDKN2A/B , 2013, Genome Biology.

[22]  E. Ostrander,et al.  A Copy Number Variant at the KITLG Locus Likely Confers Risk for Canine Squamous Cell Carcinoma of the Digit , 2013, PLoS genetics.

[23]  Sungsu Kim,et al.  Ataxin-1 occupies the promoter region of E-cadherin in vivo and activates CtBP2-repressed promoter. , 2011, Biochimica et biophysica acta.

[24]  V. Zappulli,et al.  Classification and Grading of Canine Mammary Tumors , 2011, Veterinary pathology.

[25]  F. Shofer,et al.  Canine mammary gland tumours; a histological continuum from benign to malignant; clinical and histopathological evidence. , 2009, Veterinary and comparative oncology.

[26]  J. Castle,et al.  Comparative expression pathway analysis of human and canine mammary tumors , 2009, BMC Genomics.

[27]  Xavier Estivill,et al.  SNPassoc: an R package to perform whole genome association studies , 2007, Bioinform..

[28]  E. Ostrander,et al.  The canine genome. , 2005, Genome research.

[29]  V. Moreno,et al.  Análisis estadístico de polimorfismos genéticos en estudios epidemiológicos , 2005 .