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自身免疫易感小鼠品系B10.RIII的染色体水平基因组组装

Chromosome-scale genome assembly of B10.RIII, an autoimmune susceptible mouse strain.

作者信息

Nagarajan Vijayaraj, Jittayasothorn Yingyos, Shi Guangpu, Horai Reiko, Caspi Rachel R

机构信息

Laboratory of Immunology, National Eye Institute, National Institutes of Health, 10 Center Drive, 10/10N248, Bethesda, MD 20892-1857, USA.

出版信息

bioRxiv. 2025 May 21:2025.05.16.654505. doi: 10.1101/2025.05.16.654505.

Abstract

BACKGROUND

A vast majority of potential drug candidates are initially tested in mice before human trials, resulting in life-saving treatments and preventive measures. Hundreds of autoimmune disorders, including arthritis, lupus etc., affect millions of people all over the world. Studying those disorders using mouse models is crucial for understanding the disease mechanisms. Knowing the genome sequence of these mouse models would help with those vital studies. B10.RIII is one of the most susceptible mouse strains used as a model to understand autoimmune diseases but did not have its genome sequenced until now.

FINDINGS

In this study, we generated the first, high-quality chromosome level genome sequence of B10.RIII, using a combination of long read, short read and optical mapping techniques. The B10.RIII genome sequence scored higher than the reference mouse genome both in assembly completeness and assembly quality. The B10.RIII genome annotation based on the reference genome identified about 98% of the known reference genes.

CONCLUSIONS

We believe the availability of B10.RIII genome sequence will help advance the understanding of autoimmune diseases, giving the researchers a better idea on its unique genetic makeup. Comparative studies of B10.RIII with other mouse models could also significantly enhance the power of these models towards their clinical applications.

摘要

背景

绝大多数潜在的候选药物在进行人体试验之前首先会在小鼠身上进行测试,从而带来了挽救生命的治疗方法和预防措施。包括关节炎、狼疮等在内的数百种自身免疫性疾病影响着全球数百万人。利用小鼠模型研究这些疾病对于理解疾病机制至关重要。了解这些小鼠模型的基因组序列将有助于开展这些重要研究。B10.RIII是用于理解自身免疫性疾病的最易感小鼠品系之一,但直到现在其基因组仍未测序。

研究结果

在本研究中,我们结合长读长、短读长和光学图谱技术,生成了首个高质量的B10.RIII染色体水平基因组序列。B10.RIII基因组序列在组装完整性和组装质量方面均高于参考小鼠基因组。基于参考基因组的B10.RIII基因组注释识别出了约98%的已知参考基因。

结论

我们认为B10.RIII基因组序列的可得性将有助于推进对自身免疫性疾病的理解,让研究人员更好地了解其独特的基因组成。将B10.RIII与其他小鼠模型进行比较研究也可显著增强这些模型在临床应用方面的作用。

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本文引用的文献

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Autoimmune pre-disease.自身免疫性前驱疾病。
Autoimmun Rev. 2023 Feb;22(2):103236. doi: 10.1016/j.autrev.2022.103236. Epub 2022 Nov 24.

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