The draft genome of the Wisconsin Miniature SwineTM, a valuable biomedical research tool.

IF 2.2 3区 生物学 Q3 GENETICS & HEREDITY G3: Genes|Genomes|Genetics Pub Date : 2025-06-04 DOI:10.1093/g3journal/jkaf067
Alex C Veith, Jennifer J Meudt, Jamie L Reichert, Jennifer M Frank, Derek M Pavelec, Bridget Ladell, James Speers, Molly Zeller, Taeyoung Shin, Joshua R Hyman, Christopher A Bradfield, Charles M Konsitzke, Dhanansayan Shanmuganayagam, C Dustin Rubinstein, Mark E Berres
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Abstract

Porcine biomedical models have emerged as valuable tools in biomedical research due to their physiological, anatomical, metabolic, immunological, and genetic similarities to humans. As a result, they offer greater relevance for translational studies than rodent models. Moreover, compared to nonhuman primates, porcine models are more cost-effective, easier to manipulate genetically, and raise fewer ethical concerns. However, the conventional breeds of swine most commonly used in research have rapid growth rates, which lead to logistical challenges such as increased space requirements, making them impractical as biomedical models. The Wisconsin Miniature SwineTM (WMSTM) was developed to address these shortcomings. The WMSTM porcine model grows slower, reaching and maintaining human sizes at adulthood. The model was also specifically designed to possess more human-like physiology that allows for easy modeling of comorbidities like obesity and metabolic syndrome that affect a large portion of the human population affected by chronic diseases. Thus, WMS™ is an ideal porcine gene editing platform for modeling complex multifactorial diseases. Here, we present the first draft genome assembly representative of the WMSTM line. The primary assembly was generated with ∼20× coverage of long reads from Oxford Nanopore Technologies and independently error-corrected using 23× Pacific Biosciences reads. Arima Genomics Hi-C data were used to improve contiguity. Largely congruent with the existing Sus scrofa genome, we also show the utility of WMSTM as a model through comparisons between 2 WMSTM genes and human homologs. Finally, we show the utility of genotyping by sequencing across WMSTM herds. The WMSTM genome generated here is highly complete and supports investigators utilizing WMSTM in biomedical research.

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威斯康星微型猪的基因组草图,一个有价值的生物医学研究工具。
由于猪的生理、解剖、代谢、免疫和遗传与人类相似,猪的生物医学模型已成为生物医学研究的宝贵工具。因此,与啮齿类动物模型相比,它们为转化研究提供了更大的相关性。此外,与非人类灵长类动物相比,猪模型更具成本效益,更容易进行基因操作,引起的伦理问题也更少。然而,研究中最常用的传统品种的猪生长速度很快,这导致了诸如空间需求增加等后勤挑战,使它们作为生物医学模型不切实际。威斯康辛微型猪场(WMSTM)的开发就是为了解决这些缺点。WMSTM猪模型生长较慢,成年后达到并保持人类的大小。该模型还专门设计为具有更像人类的生理学,从而可以轻松地模拟肥胖和代谢综合征等共病,这些共病影响了很大一部分受慢性疾病影响的人群。因此,WMS™是构建复杂多因子疾病模型的理想猪基因编辑平台。在这里,我们提出了WMSTM系基因组组装代表的第一个草案。最初的组装是由牛津纳米孔技术公司提供的大约20倍的长reads组成的,并使用23X Pacific Biosciences公司的reads进行了独立的错误校正。使用Arima Genomics的Hi-C数据来提高邻近度。与现有的Sus scrofa基因组基本一致,我们还通过比较两个WMSTM基因和人类同源基因来证明WMSTM作为模型的实用性。最后,我们展示了基因分型测序(GBS)在WMSTM畜群中的实用性。这里生成的WMSTM基因组是高度完整的,支持研究者在生物医学研究中利用WMSTM。
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来源期刊
G3: Genes|Genomes|Genetics
G3: Genes|Genomes|Genetics GENETICS & HEREDITY-
CiteScore
5.10
自引率
3.80%
发文量
305
审稿时长
3-8 weeks
期刊介绍: G3: Genes, Genomes, Genetics provides a forum for the publication of high‐quality foundational research, particularly research that generates useful genetic and genomic information such as genome maps, single gene studies, genome‐wide association and QTL studies, as well as genome reports, mutant screens, and advances in methods and technology. The Editorial Board of G3 believes that rapid dissemination of these data is the necessary foundation for analysis that leads to mechanistic insights. G3, published by the Genetics Society of America, meets the critical and growing need of the genetics community for rapid review and publication of important results in all areas of genetics. G3 offers the opportunity to publish the puzzling finding or to present unpublished results that may not have been submitted for review and publication due to a perceived lack of a potential high-impact finding. G3 has earned the DOAJ Seal, which is a mark of certification for open access journals, awarded by DOAJ to journals that achieve a high level of openness, adhere to Best Practice and high publishing standards.
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