GENETIC EPIDEMIOLOGY OF CRANIOSYNOSTOSIS

本申请提出了开发Simeon A的培训计划。Boyadjiev，医学博士，成为一名独立的临床科学家，临床和分子遗传学和遗传流行病学专家。自1997年10月起，Boyadjiev博士成为委员会认证的儿科医生，自1999年9月起，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基地。 培训计划将包括指导研究经验，多学科会议和高级课程工作，导致人类遗传学和遗传流行病学公共卫生硕士学位。 指导研究将作为颅面发育和疾病中心（CCDD）的成员在他的主要导师Ethylin Wang Jabs教授，医学博士，遗传医学研究所成员和CCDD主任，以及共同导师Terri Beaty博士，流行病学教授，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。 Garry Cutting教授，医学博士，约翰霍普金斯大学DNA诊断实验室主任将在该奖项的第一年担任Boyadjiev博士的临床分子遗传学培训的共同导师和指导。 该研究项目将通过对患者的临床研究进行，并利用分子和流行病学方法。 具体目标是：1）表征颅缝早闭的孤立和综合征形式; 2）收集足够数量的具有孤立颅缝早闭的病例-父母三人组以获得足够的统计功效; 3）鉴定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; 4）鉴定和测试突变和等位基因关联的候选基因和位点; 5）确定各种亚型颅缝早闭的环境风险因素;和6）开发一种有效的模型，该模型可用于分析颅缝早闭的遗传和非遗传原因以及具有复杂遗传的其他先天性异常。

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.