Kim Keon, Song Jung Eun, Joo Jae Beom, Park Hyeon A, Choi Chang Hyeon, Je Chang Yun, Kim Ock Kyu, Park Sin Wook, Do Yoon Jung, Hur Tai-Young, Park Sang-Ik, Lee Chang-Min
Department of Veterinary Internal Medicine, College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, Gwangju, Republic of Korea.
Gwangju Animal Medical Center, Gwangju, Republic of Korea.
Front Vet Sci. 2023 Oct 4;10:1255981. doi: 10.3389/fvets.2023.1255981. eCollection 2023.
A genome-wide association study (GWAS) is a valuable tool for investigating genetic and phenotypic variation in many diseases.
The objective of this study was to identify variations in the genomes of Maltese dogs that are associated with the mammary gland tumor (MGT) phenotype and to assess the association between each biological condition and MGT phenotype in Maltese dogs.
DNA was extracted from 22 tumor samples and 11 whole blood samples from dogs with MGTs. Genome-wide single-nucleotide polymorphism (SNP) genotyping was performed, and the top 20 SNPs associated with various conditions and genetic variations were mapped to their corresponding gene locations.
The genotyping process successfully identified 173,662 loci, with an overall genotype completion rate of 99.92%. Through the quality control analysis, 46,912 of these SNPs were excluded. Allelic tests were conducted to generate Manhattan plots, which showed several significant SNPs associated with MGT phenotype in intergenic region. The most prominent SNP, located within a region associated with transcription and linked to the malignancy grade of MGT, was identified on chromosome 5 ( = 0.00001) though there may be lack of statistical significance. Other SNPs were also found in several genes associated with oncogenesis, including TNFSF18, WDR3, ASIC5, STAR, and IL1RAP.
To our knowledge, this is the first GWAS to analyze the genetic predisposition to MGT in Maltese dogs. Despite the limited number of cases, these analyzed data could provide the basis for further research on the genetic predisposition to MGTs in Maltese dogs.
全基因组关联研究（GWAS）是研究多种疾病中基因和表型变异的重要工具。
本研究旨在识别与马耳他犬乳腺肿瘤（MGT）表型相关的基因组变异，并评估马耳他犬每种生物学状况与MGT表型之间的关联。
从22个患有MGT的犬类肿瘤样本和11个全血样本中提取DNA。进行全基因组单核苷酸多态性（SNP）基因分型，并将与各种状况和基因变异相关的前20个SNP映射到其相应的基因位置。
基因分型过程成功识别出173,662个位点，总体基因型完成率为99.92%。通过质量控制分析，排除了其中46,912个SNP。进行等位基因测试以生成曼哈顿图，结果显示在基因间区域有几个与MGT表型相关的显著SNP。尽管可能缺乏统计学意义，但在5号染色体上（P = 0.00001）发现了最突出的SNP，该区域与转录相关且与MGT的恶性程度有关。在几个与肿瘤发生相关的基因中也发现了其他SNP，包括TNFSF18、WDR3、ASIC5、STAR和IL1RAP。
据我们所知，这是首次对马耳他犬MGT的遗传易感性进行GWAS分析。尽管病例数量有限，但这些分析数据可为进一步研究马耳他犬MGT的遗传易感性提供基础。
