Admixture mapping in African American Asthmatic Children

非洲裔美国哮喘儿童的混合图谱

• 批准号: 7922462
• 负责人: Tesfaye B. Mersha
• 金额: $ 13.45万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-14 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7922462
• 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; 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; Research Project Grants; Resources; Risk; Risk Factors; Sampling; Science; Signal Transduction; Skin; Socioeconomic Status; Structure; Symptoms; Testing; Time; Training; Universities; Variant; Vulnerable Populations; Wisconsin; Work; abstracting; airway inflammation; base; biomedical informatics; career development; case control; cohort; database of Genotypes and Phenotypes; 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; public health relevance; racial and ethnic disparities; racial/ethnic difference; response; sex; success; tool; trait

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. PUBLIC HEALTH RELEVANCE: The burden of asthma is disproportionately high among individuals of ethnic minorities. This project aims to develop procedures and methods for utilize the genome of admixed African American populations to localize asthma liability genes by modeling individual estimates of genetic admixture and socioeconomic status on measures of asthma. By gaining a better understanding of asthma risk factors in admixed minority populations, this proposal is consistent with the goals established by Healthy People 2010, which are to eliminate health disparities among different segments of the population. (End of Abstract)

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。 公共卫生相关性：少数民族的哮喘负担特别高。该项目旨在开发程序和方法，通过对遗传混合和社会经济状况对哮喘测量的个体估计进行建模，利用混合非裔美国人群体的基因组来定位哮喘易感基因。通过更好地了解混合少数民族人群中的哮喘危险因素，该提案与《2010年健康人民》制定的目标是一致的，即消除不同人群之间的健康差异。 （摘要完）