Characterization of Tandem Repeat and Structural Variants Contributing to Addictive Behaviors in Mice and Rats

导致小鼠和大鼠成瘾行为的串联重复和结构变异的表征

基本信息

  • 批准号:
    10583503
  • 负责人:
  • 金额:
    $ 65.11万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-05-01 至 2026-02-28
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY Genome-wide association studies (GWAS) in model organisms such as mice and rats have identified hundreds of genetic loci that are associated with addictive behaviors, but determining the causal genes remains challenging. Single nucleotide polymorphisms (SNPs) may not adequately tag other classes of variants such as structural and repetitive variants that have higher mutation rates. Thus, both panels of inbred strains and outbred populations will fail to identify a subset of loci and causal alleles. We are proposing to address this serious limitation by using cutting-edge methods to discover and genotype structural variants (SVs) and tandem repeats (TRs). Because they are technically challenging to analyze, SVs and TRs have not yet been adequately surveyed in rodents. However, there is already extensive evidence that SVs and TRs are prevalent in mice and rats, and that they have important functional consequences. Our proposal brings together complementary expertise in human genetics and bioinformatic analysis of SVs (Sebat) and repetitive variation (Gymrek) with established leadership in elucidating the genetic basis of behavioral phenotypes in model organisms (Palmer). This study will generate the first large-scale resource for analyzing the effects of complex variation on mouse and rat phenotypes. We use this resource to examine gene expression and behavioral traits in inbred mice (BXD recombinant inbred strains, the Hybrid Mouse Diversity Panel (HMDP), the Diversity Outbred (DO) mice, the Hybrid Rat Diversity Panel (HRDP) and the Heterogeneous Stock (HS) outbred rats. In Specific Aim 1 we will characterize SVs in inbred and outbred mice and rats by single-molecule sequencing. In Specific Aim 2 we will genotype TR in inbred and outbred mice and rats. Finally, in Specific Aim 3 we will perform GWAS using SV and TR for gene expression and behavioral traits. We will determine the phenotypic consequences of the SV and TR genotypes on gene expression and behavioral traits. We will impute SVs and TRs into outbred mice and rats and then perform GWAS using the wealth of preexisting gene expression and behavioral data that are available for the mouse and rat populations studied in this project. Completion of this project will characterize the SV and TR landscape in mice and rats, elucidate their role in gene expression and complex behavioral traits relevant to addiction, and create a community resource that will enhance numerous ongoing mouse and rat genetic studies.
项目摘要 在模式生物如小鼠和大鼠中进行的全基因组关联研究(GWAS) 确定了数百个与成瘾行为相关的基因位点,但确定了成瘾行为的因果关系。 基因仍然具有挑战性。单核苷酸多态性(SNP)可能无法充分标记其他类别 变异体,如具有较高突变率的结构和重复变异体。因此, 近交品系和远交群体将不能鉴定基因座和致病等位基因的子集。我们 建议通过使用尖端方法来发现和基因分型, 结构变体(SV)和串联重复序列(TR)。因为它们在技术上很难分析, SV和TR尚未在啮齿动物中进行充分调查。然而,已经有广泛的 有证据表明SV和TR在小鼠和大鼠中普遍存在,并且它们具有重要的功能, 后果我们的提案汇集了人类遗传学和生物信息学方面的互补专业知识 分析SV(Sebat)和重复变异(Gymrek),在阐明 模式生物行为表型的遗传基础(Palmer)。这项研究将产生第一个 用于分析复杂变异对小鼠和大鼠表型的影响的大规模资源。我们使用 这一资源,以检查基因表达和行为性状的近交系小鼠(BXD重组近交系 品系、杂交小鼠多样性小组(HMDP)、多样性远交(DO)小鼠、杂交大鼠 多样性面板(HRDP)和异质性股票(HS)远交大鼠。 在具体目标1中,我们将通过单分子生物学方法表征近交系和远交系小鼠和大鼠中的SV 测序在特定目标2中,我们将在近交系和远交系小鼠和大鼠中对TR进行基因分型。最后在 具体目标3我们将使用SV和TR进行GWAS,用于基因表达和行为特征。我们将 确定SV和TR基因型对基因表达和行为的表型后果, 性状我们将SV和TR输入远交系小鼠和大鼠,然后使用大量的 小鼠和大鼠种群已有的基因表达和行为数据 在这个项目中研究。该项目的完成将表征小鼠的SV和TR景观, 大鼠,阐明它们在基因表达和与成瘾相关的复杂行为特征中的作用, 一个社区资源,将加强许多正在进行的小鼠和大鼠遗传研究。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Melissa Gymrek其他文献

Melissa Gymrek的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Melissa Gymrek', 18)}}的其他基金

Genome-wide characterization of complex variants and their phenotypic effects in African populations
复杂变异的全基因组特征及其在非洲人群中的表型效应
  • 批准号:
    10721811
  • 财政年份:
    2023
  • 资助金额:
    $ 65.11万
  • 项目类别:
The role of structural variants and tandem repeats in substance abuse-related behavioral traits
结构变异和串联重复在药物滥用相关行为特征中的作用
  • 批准号:
    10838864
  • 财政年份:
    2021
  • 资助金额:
    $ 65.11万
  • 项目类别:
Characterization of Tandem Repeat and Structural Variants Contributing to Addictive Behaviors in Mice and Rats
导致小鼠和大鼠成瘾行为的串联重复和结构变异的表征
  • 批准号:
    10392381
  • 财政年份:
    2021
  • 资助金额:
    $ 65.11万
  • 项目类别:
Systematic identification and interpretation of repetitive variants underlying schizophrenia
精神分裂症背后的重复变异的系统识别和解释
  • 批准号:
    10239011
  • 财政年份:
    2017
  • 资助金额:
    $ 65.11万
  • 项目类别:

相似海外基金

Strengthening behavioral and social science research capacity to address the evolving challenges in HIV care and prevention in Uganda
加强行为和社会科学研究能力,应对乌干达艾滋病毒护理和预防方面不断变化的挑战
  • 批准号:
    10872340
  • 财政年份:
    2023
  • 资助金额:
    $ 65.11万
  • 项目类别:
PARTIAL SUPPORT OF BLUEPRINT FOR A NATIONAL PREVENTION INFRASTRUCTURE TO ADDRESS BEHAVIORAL HEALTH DISORDERS: A CONSENSUS STUDY
部分支持解决行为健康障碍的国家预防基础设施蓝图:共识研究
  • 批准号:
    10954403
  • 财政年份:
    2023
  • 资助金额:
    $ 65.11万
  • 项目类别:
PARTIAL SUPPORT OF BLUEPRINT FOR A NATIONAL PREVENTION INFRASTRUCTURE TO ADDRESS BEHAVIORAL HEALTH DISORDERS: A CONSENSUS STUDY
部分支持解决行为健康障碍的国家预防基础设施蓝图:共识研究
  • 批准号:
    10936250
  • 财政年份:
    2023
  • 资助金额:
    $ 65.11万
  • 项目类别:
Control Systems Engineering to Address the Problem of Weight Loss Maintenance: A System Identification Experiment to Model Behavioral & Psychosocial Factors Measured by Ecological Momentary Assessment
解决减肥维持问题的控制系统工程:行为建模的系统识别实验
  • 批准号:
    10749979
  • 财政年份:
    2023
  • 资助金额:
    $ 65.11万
  • 项目类别:
PARTIAL SUPPORT OF BLUEPRINT FOR A NATIONAL PREVENTION INFRASTRUCTURE TO ADDRESS BEHAVIORAL HEALTH DISORDERS: A CONSENSUS STUDY
部分支持解决行为健康障碍的国家预防基础设施蓝图:共识研究
  • 批准号:
    10954098
  • 财政年份:
    2023
  • 资助金额:
    $ 65.11万
  • 项目类别:
A behavioral intervention for Black men who have sex with men and live with HIV to address intersectional stigma and improve antiretroviral therapy adherence
针对男男性行为且感染艾滋病毒的黑人男性进行行为干预,以解决交叉耻辱并提高抗逆转录病毒治疗的依从性
  • 批准号:
    10679092
  • 财政年份:
    2021
  • 资助金额:
    $ 65.11万
  • 项目类别:
A behavioral intervention for Black men who have sex with men and live with HIV to address intersectional stigma and improve antiretroviral therapy adherence
针对男男性行为且感染艾滋病毒的黑人男性进行行为干预,以解决交叉耻辱并提高抗逆转录病毒治疗的依从性
  • 批准号:
    10432133
  • 财政年份:
    2021
  • 资助金额:
    $ 65.11万
  • 项目类别:
A behavioral intervention for Black men who have sex with men and live with HIV to address intersectional stigma and improve antiretroviral therapy adherence
针对男男性行为且感染艾滋病毒的黑人男性进行行为干预,以解决交叉耻辱并提高抗逆转录病毒治疗的依从性
  • 批准号:
    10327065
  • 财政年份:
    2021
  • 资助金额:
    $ 65.11万
  • 项目类别:
The Effectiveness of Patient Navigation to Address Social and Behavioral Health Needs for Emergency Department High Utilizers.
患者导航对于满足急诊科高利用率人员的社会和行为健康需求的有效性。
  • 批准号:
    10039206
  • 财政年份:
    2020
  • 资助金额:
    $ 65.11万
  • 项目类别:
The Effectiveness of Patient Navigation to Address Social and Behavioral Health Needs for Emergency Department High Utilizers.
患者导航对于满足急诊科高利用率人员的社会和行为健康需求的有效性。
  • 批准号:
    10707128
  • 财政年份:
    2020
  • 资助金额:
    $ 65.11万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了