Admixture mapping in African American Asthmatic Children

非洲裔美国哮喘儿童的混合图谱

基本信息

批准号：
8669058
负责人：
Tesfaye B. Mersha
金额：
$ 12.85万
依托单位：
CINCINNATI CHILDRENS HOSP MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-14 至 2016-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8669058
关键词：
5q31 Academic Medical Centers Admixture Affect African African American Age Alabama Alleles American Applications Grants Architecture Asthma Biometry Candidate Disease Gene Cardiovascular Diseases Child Childhood Childhood Asthma Chromosomes Chronic Disease Clinic Complex DNA Sequence Data Data Set Databases Development Development Plans Disease Disease susceptibility Environment Environmental Exposure Epidemiology Ethnic group European Faculty Fellowship Program Fostering Generations Genes Genetic Genetic Materials Genetic Predisposition to Disease Genetic Variation Genome Genomic Segment Genomics Genotype Goals Grant Healthy People 2010 Human Genetics Hypersensitivity Individual Institution Interdisciplinary Study Journals Lead Linkage Disequilibrium Malignant neoplasm of prostate Maps Measures Medical center Methods Mexican Minority Modeling Morbidity - disease rate Multiple Sclerosis National Heart, Lung, and Blood Institute Obesity Outcome Measure Pediatric Hospitals Pediatrics Peer Review Pharmaceutical Preparations Population Population Genetics Predisposition Prevalence Procedures Publishing Puerto Rican Pulmonary function tests Quantitative Genetics Reporting Research Resources Risk Risk Factors Sampling Science Signal Transduction Socioeconomic Status Structure Symptoms Testing Time Training Universities Variant Vulnerable Populations Wisconsin Work abstracting airway inflammation base biomedical informatics career development case control cohort ethnic minority population experience follow-up gene discovery genetic variant genome-wide health disparity high risk human disease improved innovation insight interest medical schools member mortality novel professor programs racial and ethnic disparities racial/ethnic difference repository response sex skin prick test success tool trait

项目摘要

DESCRIPTION (provided by applicant): Candidate: The candidate is an Assistant Professor of Pediatrics in the Divisions of Asthma Research at Cincinnati Children's Medical Center and the University of Cincinnati. Upon completion of his quantitative genetics training, the candidate pursed statistical and human genetics fellowship programs at the University of Alabama Section on Statistical Genetics and the Human Genetics Center of Medical College of Wisconsin. These projects have been published in peer-review journals. Dr. Baye's overall research interest includes the use of quantitative and statistical genetics methods to dissect complex diseases particularly asthma and asthma-related allergy disorders. The long-term goals are to reduce childhood morbidity and mortality associated with asthma. Environment: At the Cincinnati Children's Hospital Medical center, the applicant will work with a highly collaborative multidisciplinary research team and will be fostered in an excellent academic environment offering outstanding educational programs for junior faculty members. The institution, through the Divisions of Asthma Research, Asthma Center, Biostatistics and Epidemiology, Biomedical Informatics and the Genetic Variation and Gene Discovery Core, provides all resources and facilities that are needed for the applicant's proposed research and is providing full access to all necessary resources to the applicant. The applicant will be provided 90% protected time to conduct the research proposed in this application. Research: This project aims to develop a program of study that would lead to an in depth understanding of the genome of African American (AA) admixed populations and develop procedures and methods for utilizing this information and SNP markers for linkage disequilibrium admixture mapping to localize asthma liability genes. The burden of asthma is disproportionately high among individuals of African descent. Due to recent admixture, AAs have a mixed parental genome contribution, with an average ratio of 80:20 for the proportion from African descent and European descent. This generates linkage disequilibrium (LD) among alleles on all chromosomes, which is detectable even at substantial distances (20-30 cM) using Ancestry Informative Markers (AIMs). We plan to develop methods to exploit this LD that span along the genomes of AAs with asthma, in search for specific regions of unusually high African or European ancestry, thereby identifying the chromosomal segments that are likely to contain genes that are related to the disease liability. To achieve these goals, the following specific aims are proposed: 1) Investigate the genome of African American admixed population using our recently developed ancestry informative markers (Baye et al., 2009); 2) Estimate admixture proportions and evaluate differences between asthma cases and controls; 3) Apply these procedures to investigate whether genetic ancestral background at the 5q31 region is associated with asthma outcome measures. Hence, genotypic data from HapMap, Perlegen datasets and Greater Cincinnati Pediatric Clinic Cohort will be used to test the approach and enhance our ability to map asthma liability genes. Implications: This career development plan will foster Dr. Baye's development into an established independent expertise in complex disease and asthma genetics. The research will improve mapping of loci affecting complex traits in admixed populations, ultimately improving elucidation of the genetic architecture of complex human diseases.

描述（由申请人提供）：候选人：候选人是辛辛那提儿童医学中心和辛辛那提大学哮喘研究部门的儿科助理教授。完成定量遗传学培训后，该候选人在阿拉巴马大学统计遗传学科和威斯康星医学院人类遗传学中心攻读统计和人类遗传学奖学金项目。这些项目已发表在同行评审期刊上。 Baye 博士的总体研究兴趣包括使用定量和统计遗传学方法来剖析复杂疾病，特别是哮喘和哮喘相关的过敏性疾病。长期目标是降低与哮喘相关的儿童发病率和死亡率。环境：在辛辛那提儿童医院医疗中心，申请人将与高度协作的多学科研究团队合作，并在优良的学术环境中成长，为初级教员提供出色的教育项目。该机构通过哮喘研究、哮喘中心、生物统计和流行病学、生物医学信息学以及遗传变异和基因发现核心部门，提供申请人拟议研究所需的所有资源和设施，并提供对所有必要资源的全面访问给申请人。申请人将获得 90% 的受保护时间来进行本申请中提出的研究。研究：该项目旨在制定一项研究计划，深入了解非裔美国人 (AA) 混合人群的基因组，并开发利用该信息和 SNP 标记进行连锁不平衡混合图谱定位哮喘的程序和方法责任基因。非洲人后裔的哮喘负担异常高。由于最近的混合，AA 具有混合的亲本基因组贡献，非洲血统和欧洲血统的平均比例为 80:20。这会在所有染色体上的等位基因之间产生连锁不平衡 (LD)，即使在很远的距离 (20-30 cM) 下，也可以使用祖先信息标记 (AIM) 检测到连锁不平衡。我们计划开发方法来利用这种跨哮喘 AA 基因组的 LD，寻找异常高的非洲或欧洲血统的特定区域，从而识别可能包含与疾病易感性相关基因的染色体片段。为了实现这些目标，提出了以下具体目标： 1）使用我们最近开发的祖先信息标记来研究非裔美国人混合人群的基因组（Baye et al., 2009）； 2) 估计混合比例并评估哮喘病例和对照之间的差异； 3) 应用这些程序来调查 5q31 区域的遗传祖先背景是否与哮喘结果指标相关。因此，来自 HapMap、Perlegen 数据集和大辛辛那提儿科诊所队列的基因型数据将用于测试该方法并增强我们绘制哮喘易感基因图谱的能力。含义：该职业发展计划将促进 Baye 博士发展成为复杂疾病和哮喘遗传学领域的独立专业知识。该研究将改善影响混合人群复杂性状的基因座图谱，最终改善复杂人类疾病遗传结构的阐明。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Multiple Transcriptome Data Analysis Reveals Biologically Relevant Atopic Dermatitis Signature Genes and Pathways.

多转录组数据分析揭示了生物学相关的特应性皮炎特征基因和途径。

DOI：
发表时间：
2015
期刊：
影响因子：
3.7
作者：
Ghosh, Debajyoti;Ding, Lili;Sivaprasad, Umasundari;Geh, Esmond;Biagini Myers, Jocelyn;Bernstein, Jonathan A;Khurana Hershey, Gurjit K;Mersha, Tesfaye B
通讯作者：
Mersha, Tesfaye B

Population Genomics and the Statistical Values of Race: An Interdisciplinary Perspective on the Biological Classification of Human Populations and Implications for Clinical Genetic Epidemiological Research.

群体基因组学和种族的统计价值：人类群体生物学分类的跨学科视角及其对临床遗传流行病学研究的影响。