Vijayakumar Vishwaarth, Joshi Tanvi, Elkhadragy Lobna, Schook Lawrence B, Gaba Ron C, El-Kebir Mohammed, Schachtschneider Kyle M
Carle Illinois College of Medicine, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Department of Animal Sciences, University of Illinois at Urbana-Champaign, Champaign, IL, USA.
Genome Biol. 2025 May 8;26(1):118. doi: 10.1186/s13059-025-03589-4.
It is important for porcine models to replicate gene mutations present in human diseases to improve the translatability of animal studies. In this study, the high efficacy of a whole exome sequencing kit was demonstrated for the improved pig reference genome (Sus scrofa 11.1) to profile biomedically relevant swine breeds and enable high-depth sequencing required for intratumor heterogeneity profiling.
We identify a total of 751,624 single nucleotide variants (SNVs) and 113,597 insertions and deletions (INDELs) across 93 samples from 12 porcine breeds. The identified mutations and affected pathways are correlated to muscle-to-fat ratios between different porcine breeds and further inform their utility as models of obesity and cardiovascular disease. Finally, 7935 SNVs and 358 INDELs are present in an Oncopig hepatocellular carcinoma (HCC) cell line and samples from a single Oncopig HCC tumor, with pathways related to hepatic fibrosis, WNT/B-catenin, ATM signaling, and p53 signaling enriched.
These results demonstrate the kit's high efficacy and utility for identifying mutations in the context of obesity, cardiovascular disease, and cancer across a range of pig models used in biomedical research.
猪模型复制人类疾病中存在的基因突变对于提高动物研究的可转化性很重要。在本研究中，全外显子测序试剂盒在改良猪参考基因组（猪11.1）上展现出高效能，可用于分析具有生物医学相关性的猪品种，并实现肿瘤内异质性分析所需的深度测序。
我们在来自12个猪品种的93个样本中总共鉴定出751,624个单核苷酸变异（SNV）和113,597个插入和缺失（INDEL）。所鉴定的突变及受影响的通路与不同猪品种之间的肌肉脂肪比相关，并进一步说明了它们作为肥胖和心血管疾病模型的效用。最后，在一种抗癌猪肝细胞癌（HCC）细胞系以及单个抗癌猪HCC肿瘤的样本中存在7935个SNV和358个INDEL，其中与肝纤维化、WNT/β-连环蛋白、ATM信号传导和p53信号传导相关的通路得到了富集。
这些结果证明了该试剂盒在识别一系列用于生物医学研究的猪模型中的肥胖、心血管疾病和癌症相关突变方面的高效能和实用性。
