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常见绒猴()中 SNV 和 Indel 多态性的全基因组分析。

Whole Genome Analysis of SNV and Indel Polymorphism in Common Marmosets ().

机构信息

Human Genome Sequencing Center and Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.

Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USA.

出版信息

Genes (Basel). 2023 Dec 7;14(12):2185. doi: 10.3390/genes14122185.

Abstract

The common marmoset () is one of the most widely used nonhuman primate models of human disease. Owing to limitations in sequencing technology, early genome assemblies of this species using short-read sequencing suffered from gaps. In addition, the genetic diversity of the species has not yet been adequately explored. Using long-read genome sequencing and expert annotation, we generated a high-quality genome resource creating a 2.898 Gb marmoset genome in which most of the euchromatin portion is assembled contiguously (contig N50 = 25.23 Mbp, scaffold N50 = 98.2 Mbp). We then performed whole genome sequencing on 84 marmosets sampling the genetic diversity from several marmoset research centers. We identified a total of 19.1 million single nucleotide variants (SNVs), of which 11.9 million can be reliably mapped to orthologous locations in the human genome. We also observed 2.8 million small insertion/deletion variants. This dataset includes an average of 5.4 million SNVs per marmoset individual and a total of 74,088 missense variants in protein-coding genes. Of the 4956 variants orthologous to human ClinVar SNVs (present in the same annotated gene and with the same functional consequence in marmoset and human), 27 have a clinical significance of pathogenic and/or likely pathogenic. This important marmoset genomic resource will help guide genetic analyses of natural variation, the discovery of spontaneous functional variation relevant to human disease models, and the development of genetically engineered marmoset disease models.

摘要

普通狨猴(Callithrix jacchus)是人类疾病最广泛使用的非人类灵长类动物模型之一。由于测序技术的限制,早期使用短读测序技术对该物种进行的基因组组装存在缺口。此外,该物种的遗传多样性尚未得到充分探索。通过长读基因组测序和专家注释,我们生成了一个高质量的基因组资源,创建了一个 2.898 Gb 的狨猴基因组,其中大部分常染色质部分连续组装(contig N50 = 25.23 Mbp,scaffold N50 = 98.2 Mbp)。然后,我们对 84 只狨猴进行了全基因组测序,这些狨猴来自几个狨猴研究中心,代表了不同的遗传多样性。我们总共鉴定了 1910 万个单核苷酸变异(SNVs),其中 1190 万个可以可靠地映射到人类基因组的同源位置。我们还观察到 280 万个小插入/缺失变异。该数据集包括每只狨猴平均 540 万个 SNVs 和编码蛋白的基因中总共 74088 个错义变异。在与人类 ClinVar SNVs (在狨猴和人类中存在于相同注释基因中且具有相同功能后果)同源的 4956 个变异中,有 27 个具有致病性和/或可能致病性的临床意义。这个重要的狨猴基因组资源将有助于指导对自然变异的遗传分析、发现与人类疾病模型相关的自发功能变异以及开发基因工程狨猴疾病模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6325/10742769/491e5994af6d/genes-14-02185-g001.jpg

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