A long term resource to maximise the potential of laboratory mouse strains for medical research

最大限度发挥实验室小鼠品系用于医学研究的潜力的长期资源

基本信息

  • 批准号:
    BB/M000281/1
  • 负责人:
  • 金额:
    $ 85.98万
  • 依托单位:
  • 依托单位国家:
    英国
  • 项目类别:
    Research Grant
  • 财政年份:
    2015
  • 资助国家:
    英国
  • 起止时间:
    2015 至 无数据
  • 项目状态:
    已结题

项目摘要

Our key aim is to explore the relationship between genetic and medically relevant human disease phenotypes. One way to do this is to assess the genetic differences between long-established laboratory mouse strains. Laboratory mouse strains display many important disease phenotypes such as resistance to various forms of cancer (e.g. liver, lung, and skin cancer), bacterial, and viral infection and are used as models for many human diseases. The foundation for studying the genetic differences in these strains is having accurate genome sequences. In this project, we will first generate genome sequences for the most commonly used laboratory mouse strains and then use these sequences and knowledge of the gene structures to determine the genetic cause of observed disease response and behaviour differences between these strains. By combining sequence and phenotypic data we will determine whether sequence variants are likely to be contributing to disease susceptibility.The main aim of this project is to correctly identify all the genes on the newly completed release of genome sequences of 12 laboratory mouse strains. This is achieved in a combination of two strategies. Initially the genes will be identified using state of the art bioinformatic programs and pipelines. The genes are identified by matches to known mouse proteins on the genome, other transcribed data such at mRNAs and ESTs or conserved proteins from other species. As this is an automatic pipeline, there will be complex gene families that cannot be correctly identified and require manual inspection. The HAVANA team have been involved in manual annotation of the human, mouse and zebrafish reference genomes and have developed in-house specialist tools to help accurate identification of genes within different genomes. Since manual inspection is expensive and time consuming the manual effort will be targeted on complex gene families and genes of specific interest to the mouse scientific research community. Engaging with the community will be essential to receive feedback about targeting of annotation as well as to generate community participation in the manual inspection of genes of interest. Automatic annotation identifies around 70% of genes correctly, therefore the aim would be to use bioinformatics analysis and feedback from researchers to target the 30% incorrectly annotated genes and improve them.
我们的主要目的是探索遗传和医学相关的人类疾病表型之间的关系。一种方法是评估长期建立的实验室小鼠品系之间的遗传差异。实验室小鼠品系显示出许多重要的疾病表型,例如对各种形式的癌症(例如肝癌、肺癌和皮肤癌)、细菌和病毒感染的抗性,并且用作许多人类疾病的模型。研究这些菌株遗传差异的基础是获得准确的基因组序列。在这个项目中,我们将首先生成最常用的实验室小鼠品系的基因组序列,然后使用这些序列和基因结构的知识来确定这些品系之间观察到的疾病反应和行为差异的遗传原因。通过结合序列和表型数据,我们将确定序列变异是否可能导致疾病易感性。该项目的主要目的是正确识别新完成的12种实验室小鼠品系基因组序列中的所有基因。这是通过两种战略的结合来实现的。最初,将使用最先进的生物信息学程序和管道来识别基因。这些基因通过与基因组上已知的小鼠蛋白质、其他转录数据如mRNA和EST或来自其他物种的保守蛋白质的匹配来鉴定。由于这是一个自动化的管道,将有复杂的基因家族无法正确识别,需要人工检查。HAVANA团队参与了人类、小鼠和斑马鱼参考基因组的手动注释,并开发了内部专业工具,以帮助准确识别不同基因组中的基因。由于人工检查昂贵且耗时,因此人工工作将针对复杂的基因家族和小鼠科学研究界特别感兴趣的基因。与社区的互动对于获得关于注释靶向的反馈以及促使社区参与感兴趣基因的手动检查至关重要。自动注释可以正确识别大约70%的基因,因此,目标是利用生物信息学分析和研究人员的反馈来定位30%错误注释的基因并对其进行改进。

项目成果

期刊论文数量(10)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Deep genome sequencing and variation analysis of 13 inbred mouse strains defines candidate phenotypic alleles, private variation, and homozygous truncating mutations
13 个近交小鼠品系的深度基因组测序和变异分析定义了候选表型等位基因、私人变异和纯合截短突变
  • DOI:
    10.1101/039131
  • 发表时间:
    2016
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Doran A
  • 通讯作者:
    Doran A
Deep genome sequencing and variation analysis of 13 inbred mouse strains defines candidate phenotypic alleles, private variation and homozygous truncating mutations.
  • DOI:
    10.1186/s13059-016-1024-y
  • 发表时间:
    2016-08-01
  • 期刊:
  • 影响因子:
    12.3
  • 作者:
    Doran AG;Wong K;Flint J;Adams DJ;Hunter KW;Keane TM
  • 通讯作者:
    Keane TM
A Requirement for Zic2 in the Regulation of Nodal Expression Underlies the Establishment of Left-Sided Identity.
  • DOI:
    10.1038/s41598-018-28714-1
  • 发表时间:
    2018-07-11
  • 期刊:
  • 影响因子:
    4.6
  • 作者:
    Dykes IM;Szumska D;Kuncheria L;Puliyadi R;Chen CM;Papanayotou C;Lockstone H;Dubourg C;David V;Schneider JE;Keane TM;Adams DJ;Brown SDM;Mercier S;Odent S;Collignon J;Bhattacharya S
  • 通讯作者:
    Bhattacharya S
Comparative Annotation Toolkit (CAT)-simultaneous clade and personal genome annotation.
  • DOI:
    10.1101/gr.233460.117
  • 发表时间:
    2018-07
  • 期刊:
  • 影响因子:
    7
  • 作者:
    Fiddes IT;Armstrong J;Diekhans M;Nachtweide S;Kronenberg ZN;Underwood JG;Gordon D;Earl D;Keane T;Eichler EE;Haussler D;Stanke M;Paten B
  • 通讯作者:
    Paten B
Additional file 2: of Deep genome sequencing and variation analysis of 13 inbred mouse strains defines candidate phenotypic alleles, private variation and homozygous truncating mutations
附加文件 2:13 个近交小鼠品系的深度基因组测序和变异分析定义了候选表型等位基因、私有变异和纯合截断突变
  • DOI:
    10.6084/m9.figshare.c.3643385_d6
  • 发表时间:
    2016
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Doran A
  • 通讯作者:
    Doran A
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David Adams其他文献

Patients with a gene encoding a truncated ADP-ribosyl-acceptor hydrolase 3 exhibit a progressive neurodegenerative phenotype
携带编码截短 ADP-核糖基-受体水解酶 3 基因的患者表现出进行性神经退行性表型
  • DOI:
  • 发表时间:
    2019
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Masato Mashimo;Xiangning Bu;Kazumasa Aoyama;Jiro Kato;Hiroko Ishiwata-Endo;Linda A. Stevens;Atsushi Kasamatsu;Lynne A. Wolfe;Camilo Toro;David Adams;Thomas Markello;William A. Gahl;Joel Moss
  • 通讯作者:
    Joel Moss
Findings in an Unusual MELAS Case Tracking, and Single-Voxel Spectroscopy MR Diffusion Tensor Imaging, Fiber
不寻常的 MELAS 病例追踪和单体素能谱 MR 扩散张量成像、光纤的发现
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
    D. Ducreux;G. Nasser;Catherine Lacroix;David Adams;P. Lasjaunias
  • 通讯作者:
    P. Lasjaunias
Contesting urban monuments: future directions for the controversial monumental landscapes of civic grandeur
有争议的城市纪念碑:有争议的城市宏伟纪念碑景观的未来方向
An Integrated Approach to Developing Technical Communication Skills in Engineering Students
培养工程学生技术沟通技能的综合方法
  • DOI:
  • 发表时间:
    2014
  • 期刊:
  • 影响因子:
    0
  • 作者:
    R. Harichandran;D. Adams;David Adams;M. Collura
  • 通讯作者:
    M. Collura
AN ANTIFRAGILE SYSTEM FOR REDUCING PHYSICIAN BURNOUT
减少医生倦怠的抗脆弱系统
  • DOI:
  • 发表时间:
    2017
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Mitchell H. Tsai;Imelda R. Muller;Shelly R. Stelzer;R. Urman;David Adams
  • 通讯作者:
    David Adams

David Adams的其他文献

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{{ truncateString('David Adams', 18)}}的其他基金

The Genomic Atlas of Dermatological Tumours (DERMATLAS)
皮肤肿瘤基因组图谱 (DERMATLAS)
  • 批准号:
    MR/V000292/1
  • 财政年份:
    2021
  • 资助金额:
    $ 85.98万
  • 项目类别:
    Research Grant
Identifying the drivers and vulnerabilities of acral lentiginous melanoma through the study of PDX models from Latin American patients
通过研究拉丁美洲患者的 PDX 模型来确定肢端雀斑样黑色素瘤的驱动因素和脆弱性
  • 批准号:
    MR/S01473X/1
  • 财政年份:
    2018
  • 资助金额:
    $ 85.98万
  • 项目类别:
    Research Grant
Integrating innovative technologies for genotyping and phenotyping in stratified medicine
在分层医学中整合基因分型和表型分型的创新技术
  • 批准号:
    MR/M009157/1
  • 财政年份:
    2015
  • 资助金额:
    $ 85.98万
  • 项目类别:
    Research Grant
University of Birmingham MRC Proximity to Discovery: Open Innovation Through LocalIntegration
伯明翰大学 MRC 接近发现:通过本地整合进行开放式创新
  • 批准号:
    MC_PC_14123
  • 财政年份:
    2015
  • 资助金额:
    $ 85.98万
  • 项目类别:
    Intramural
Maximising the potential of wild-derived laboratory mouse strains for medical research
最大限度地发挥野生实验室小鼠品系在医学研究中的潜力
  • 批准号:
    MR/L007428/1
  • 财政年份:
    2014
  • 资助金额:
    $ 85.98万
  • 项目类别:
    Research Grant
Trafficking of monocytes and their differentiation to dendritic cells and macrophages in the human liver
人肝脏中单核细胞的贩运及其分化为树突状细胞和巨噬细胞
  • 批准号:
    G0700301/1
  • 财政年份:
    2007
  • 资助金额:
    $ 85.98万
  • 项目类别:
    Research Grant
The iBAC genomic DNA expression library
iBAC 基因组 DNA 表达文库
  • 批准号:
    BB/D012759/1
  • 财政年份:
    2006
  • 资助金额:
    $ 85.98万
  • 项目类别:
    Research Grant
Issues-Directed Introductory Chemistry for Business Students
面向商科学生的问题导向化学入门课程
  • 批准号:
    9150553
  • 财政年份:
    1991
  • 资助金额:
    $ 85.98万
  • 项目类别:
    Standard Grant
Mathematical Sciences: Theory of Capacities
数学科学:能力理论
  • 批准号:
    8702755
  • 财政年份:
    1987
  • 资助金额:
    $ 85.98万
  • 项目类别:
    Standard Grant
Some Questions in Potential Theory and Partial Differential Equations Related to the Lp-Theory of Capacities
势论和偏微分方程中与Lp-容量理论相关的一些问题
  • 批准号:
    8002840
  • 财政年份:
    1980
  • 资助金额:
    $ 85.98万
  • 项目类别:
    Standard Grant

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区域碳交易试点的运行机制及其经济影响研究---基于Term-Co2模型
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