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的儿科助理教授。在完成他的定量遗传学培训后，候选人在亚拉巴马大学统计遗传学部和威斯康星州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。这些项目已在同行评审期刊上发表。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的疾病，特别是哮喘和哮喘相关的过敏性疾病。长期目标是减少与哮喘有关的儿童发病率和死亡率。工作环境：在辛辛那提儿童医院医疗中心，申请人将与一个高度协作的多学科研究团队合作，并将在一个优秀的学术环境中培养，为初级教师提供优秀的教育课程。该机构通过哮喘研究、哮喘中心、生物统计学和流行病学、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，并向申请人提供所有必要资源的全面访问权。申请人将获得90%的保护时间来进行本申请中提出的研究。调研：该项目旨在开发一个研究计划，深入了解非洲裔美国人（AA）混合人群的基因组，并开发利用这些信息和SNP标记进行连锁不平衡混合作图以定位哮喘易感基因的程序和方法。哮喘病在非洲人后裔中的负担特别高。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比例平均为80：20。这在所有染色体上的等位基因之间产生连锁不平衡（LD），这甚至在相当大的距离（20-30 cM）处使用遗传信息标记（AIM）也是可检测的。我们计划开发方法来利用这种LD，跨越沿着哮喘AA的基因组，在寻找异常高的非洲或欧洲血统的特定区域，从而确定可能包含与疾病易感性相关的基因的染色体片段。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（Baye et al.，2009年）; 2）估计混合比例，并评估哮喘病例和对照组之间的差异; 3）应用这些程序来调查5 q31区域的遗传祖先背景是否与哮喘结局指标相关。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的能力。含义：这个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方面的独立专家。这项研究将改善影响混合人群中复杂性状的基因座的定位，最终改善对复杂人类疾病遗传结构的阐明。 公共卫生相关性：哮喘的负担在少数民族中不成比例地高。该项目旨在开发程序和方法，利用混合的非洲裔美国人的基因组定位哮喘易感基因的遗传混合和社会经济地位的措施，哮喘的个人估计建模。通过更好地了解混合少数民族人群中的哮喘风险因素，该提案符合2010年健康人制定的目标，即消除不同人群之间的健康差距。(End摘要）