GENETIC EPIDEMIOLOGY OF CRANIOSYNOSTOSIS

该申请提出了一项培训计划，旨在培养医学博士Simeon a . Boyadjiev成为一名独立的临床科学家，临床和分子遗传学以及遗传流行病学方面的专家。1997年10月以来，Boyadjiev博士是董事会认证的儿科医生，1999年9月，他被美国医学遗传学委员会认证为临床遗传学家。约翰霍普金斯大学非常适合作为他的训练地点。培训计划将包括指导研究经验，多学科会议和高级课程，最终获得人类遗传学和遗传流行病学公共卫生硕士学位。他将作为颅面发育和疾病中心（CCDD）的成员，在其主要导师遗传医学研究所成员兼CCDD主任Ethylin Wang Jabs教授和共同导师Terri Beaty博士（流行病学教授兼卫生与公共卫生学院人类遗传学和遗传流行病学项目主任）的指导下进行研究。约翰霍普金斯大学DNA诊断实验室主任、医学博士Garry Cutting教授将担任Boyadjiev博士的联合导师，并在该奖项的第一年指导Boyadjiev博士的临床分子遗传学培训。该研究计划将透过临床病人研究及运用分子及流行病学方法进行。具体目的是：1)表征孤立和综合征形式的颅缝闭锁；2)收集足够数量的孤立性颅缝闭闭病例-父母三人组，以达到足够的统计效力；3)识别和利用新的和现有的单核苷酸多态性（SNP），以建立与特定染色体区域的连锁关系；4)鉴定和检测候选突变基因和等位基因关联位点；5)确定不同类型颅缝闭锁的环境危险因素；6)建立一种有效的模型，用于分析颅缝闭闭及其他遗传复杂的先天性异常的遗传和非遗传原因。

This application proposes a training plan to develop Simeon A. Boyadjiev, M.D., into an independent clinical scientist, expert in clinical and molecular genetics and genetic epidemiology. Since October 1997, Dr. Boyadjiev is a board certified Pediatrician and as of September 1999, he is certified as a Clinical Geneticist by The American Board of Medical Genetics. The Johns Hopkins University is exceptionally well suited to serve as his training site. The training program will consist of mentored research experience, multi-disciplinary conferences, and advanced course work, leading to a Master of Public Health degree in Human Genetics and Genetic Epidemiology. Mentored research will be conducted as a member of the Center for Craniofacial Development and Disorders (CCDD) under his primary mentor Prof. Ethylin Wang Jabs, M.D., member of the Institute of Genetic Medicine and Director of CCDD, and co-mentor Terri Beaty, Ph.D., Professor of Epidemiology and Director of the Human Genetics and Genetic Epidemiology program at the School of Hygiene and Public Health. Prof. Garry Cutting, M.D., Director of the DNA Diagnostic Laboratory at Johns Hopkins will serve as a co-mentor and direct Dr. Boyadjiev's training in Clinical Molecular Genetics during the first year of the award. The research project will be conducted through clinic-based study of patients and utilize molecular and epidemiologic methodologies. The specific aims are: 1) to characterize isolated and syndromic forms of craniosynostosis; 2) to collect a sufficient number of case-parent trios with isolated craniosynostosis in order to achieve sufficient statistical power; 3) to identify and utilize new and existing single nucleotide polymorphisms (SNP) in order to establish linkage to specific chromosomal regions; 4) to identify and test candidate genes and loci for mutations and allelic associations; 5) to identify environmental risk factors for various subtypes of craniosynostosis; and 6) to develop an efficient model that can be applied toward the analysis of genetic and non-genetic causes of craniosynostosis as well as other congenital anomalies with complex inheritance.