Rapid construction of reference chromosome-level mammalian genome assemblies and insights into the mechanisms of gross genomic rearrangement
快速构建参考染色体水平哺乳动物基因组组装并深入了解总基因组重排机制
基本信息
- 批准号:BB/P020062/1
- 负责人:
- 金额:$ 40.15万
- 依托单位:
- 依托单位国家:英国
- 项目类别:Research Grant
- 财政年份:2017
- 资助国家:英国
- 起止时间:2017 至 无数据
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
We live in an era in which the genomes of new species are being sequenced all the time. The most modern ways to sequence DNA have many advantages over older approaches (the prominent one being a vastly reduced cost) but a problem that arises each time the genome of a new species is sequenced is that assigning large blocks of sequence to an overall genomic "map" can be problematic and/or very expensive. It's a little like finding your location on Google Maps but not being able to "zoom out" to establish where that position is in relation to the whole country. In essence the aim of this project is to rectify this problem at one fifth of the current cost. Using our experience with birds we have developed a high-throughput approach and the tools for assigning the sequences to their proper positions in chromosomes. This involves our own adaptations to a technique called "FISH" that can take the data from sequenced genomes and visualize directly blocks of DNA sequence as they appear in their rightful place in the genome. In this study we will focus our attention on 25 newly sequenced mammal species. More importantly however we will provide the means through which this can be achieved for any of the 5,000 living mammalian species. Mammals are important to our lives in that many are models for human disease and development and are critical to agriculture (both meat and milk). Others are threatened or endangered and, with impending global warming, molecular tools for the study of their ecology and conservation are essential. Our combined efforts have also developed computer-based browser methods to compare the overall structure of one genome with another, directly visualizing the similarities and differences between the genomes of several animals at a time, something we can share widely amongst the scientific community and general public via the world wide web. The differences between mammalian genomes arose through changes that happened during evolution. One of the main aims of this project is to find out how this occurred and what are implications of these changes. We have a number of ideas such as we think there may be different "signatures" that classify why blocks of genes tend to stay together during evolution. Armed with this information, we fully intend to take it out into the world. The devices that we will develop can be adapted for the screening of individual animals for genomic rearrangements that may cause e.g. breeding problems. Moreover, the resources we will develop provide a source for public information and student learning through a dedicated, outwardly-facing web site. We have received overwhelming support from numerous laboratories all over the world who are interested in using the resources that we will develop to ask biological questions of their own. For this reason, we feel that this project will help us understand evolution in mammals and contribute to establishing the UK as a central international hub of mammalian genomics.
我们生活在一个新物种的基因组一直在被测序的时代。与旧方法相比,最现代的DNA测序方法有许多优势(最突出的是成本大大降低),但每次对新物种的基因组进行测序时,出现的一个问题是,将大块序列分配给整个基因组“图谱”可能会有问题和/或非常昂贵。这有点像在谷歌地图上找到你的位置,但不能“缩小”来确定该位置相对于整个国家的位置。从本质上讲,该项目的目的是以当前费用的五分之一纠正这一问题。利用我们在鸟类方面的经验,我们已经开发出一种高通量的方法和工具,用于将序列分配到它们在染色体中的适当位置。这涉及到我们自己对一种名为“FISH”的技术的适应,这种技术可以从测序的基因组中获取数据,并在DNA序列出现在基因组中的正确位置时直接将其可视化。在这项研究中,我们将重点关注25个新测序的哺乳动物物种。然而,更重要的是,我们将为5000种现存哺乳动物中的任何一种提供实现这一目标的手段。哺乳动物对我们的生活很重要,因为许多哺乳动物是人类疾病和发育的模型,对农业(包括肉类和牛奶)至关重要。其他物种受到威胁或濒临灭绝,随着全球变暖的迫在眉睫,研究它们的生态和保护的分子工具至关重要。我们的共同努力还开发了基于计算机的浏览器方法,以比较一个基因组与另一个基因组的整体结构,一次直接显示几种动物基因组之间的相似和差异,这是我们可以通过万维网在科学界和普通公众中广泛共享的东西。哺乳动物基因组之间的差异是由进化过程中发生的变化引起的。这个项目的主要目标之一是找出这种情况是如何发生的,以及这些变化的影响是什么。我们有许多想法,比如我们认为可能有不同的“签名”来分类为什么基因块在进化过程中往往保持在一起。有了这些信息,我们完全打算把它带到世界上去。我们将开发的设备可以用于筛选单个动物的基因组重排,这可能会导致例如繁殖问题。此外,我们将开发的资源通过一个专门的、面向外部的网站提供公共信息和学生学习的来源。我们得到了世界各地许多实验室的压倒性支持,他们有兴趣利用我们将开发的资源来提出他们自己的生物学问题。因此,我们认为这个项目将帮助我们了解哺乳动物的进化,并有助于将英国建立为哺乳动物基因组学的中心国际中心。
项目成果
期刊论文数量(6)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
G-Anchor: a novel approach for whole-genome comparative mapping utilizing evolutionary conserved DNA sequences.
- DOI:10.1093/gigascience/giy017
- 发表时间:2018-05-01
- 期刊:
- 影响因子:9.2
- 作者:Lenis VPE;Swain M;Larkin DM
- 通讯作者:Larkin DM
A Near Chromosome Assembly of the Dromedary Camel Genome
- DOI:10.3389/fgene.2019.00032
- 发表时间:2019-02
- 期刊:
- 影响因子:3.7
- 作者:D. Ruvinskiy;D. Larkin;M. Farré
- 通讯作者:D. Ruvinskiy;D. Larkin;M. Farré
Evolution of gene regulation in ruminants differs between evolutionary breakpoint regions and homologous synteny blocks
- DOI:10.1101/gr.239863.118
- 发表时间:2019-04-01
- 期刊:
- 影响因子:7
- 作者:Farre, Marta;Kim, Jaebum;Larkin, Denis M.
- 通讯作者:Larkin, Denis M.
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Denis Larkin其他文献
Denis Larkin的其他文献
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{{ truncateString('Denis Larkin', 18)}}的其他基金
Using reference-assisted chromosome assemblies to study chromosome structures and evolution in vertebrates
使用参考辅助染色体组装来研究脊椎动物的染色体结构和进化
- 批准号:
BB/J010170/2 - 财政年份:2013
- 资助金额:
$ 40.15万 - 项目类别:
Research Grant
Genome assembly. chromosomal organization and comparative genomics of multiple bird species: beyond "catalogues of genes"
基因组组装。
- 批准号:
BB/K008226/1 - 财政年份:2013
- 资助金额:
$ 40.15万 - 项目类别:
Research Grant
Genome assembly. chromosomal organization and comparative genomics of multiple bird species: beyond "catalogues of genes"
基因组组装。
- 批准号:
BB/K008226/2 - 财政年份:2013
- 资助金额:
$ 40.15万 - 项目类别:
Research Grant
Using reference-assisted chromosome assemblies to study chromosome structures and evolution in vertebrates
使用参考辅助染色体组装来研究脊椎动物的染色体结构和进化
- 批准号:
BB/J010170/1 - 财政年份:2012
- 资助金额:
$ 40.15万 - 项目类别:
Research Grant
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