The Burden of Genetic Disorders in Infant Mortality

项目摘要/摘要 遗传性疾病和先天畸形可能是遗传性的，是主要原因。 美国的婴儿死亡率。然而，我们仍然不能完全了解哪些基因 疾病是造成婴儿死亡及其全部影响的罪魁祸首。这台NIH K23 研究提案代表了一项多学科的努力，以进一步了解 基因对婴儿死亡率的贡献，利用沃伊奇克博士已经拥有的专业知识 通过临床遗传学和新生儿-围产期医学的双重培训获得 提供基因组分析、流行病学和生物统计学以及临床方面的进一步培训 研究性学习设计。建立在沃伊奇克博士先前关于基因影响的研究的基础上 婴儿期诊断与小说外显组分析的体会 疾病基因发现，这项研究的目的是确定孟德尔病的患病率 死亡婴儿队列中的遗传性疾病(目标1)和评估公共卫生 使用父母调查数据(目标2)和从以下方面获得的数据进行诊断的影响 国家卫生统计中心(目标3)。在国际公认的 新生儿学和基因组医学专家(Pankaj Agrawal，MD，MSSC)，人类遗传学 和罕见疾病基因发现(Heidi Rehm，PhD)，伦理/法律/社会影响 临床遗传学(英格丽德·霍尔姆，医学博士，公共卫生硕士)，并与父母悲伤方面的专家合作 失去婴儿(理查德·戈尔茨坦，医学博士)，临床遗传学(文翰·谭文汉，MBBS)， 围产期死亡率/流行病学(多米尼克·海因克，SCD)，其他研究和职业 来自人类基因组学成功研究人员的指导(艾伦·贝格斯、博士和罗伯特 沃伊奇克博士将努力为失去亲人的家庭提供答案。同时， 她将获得作为一名独立临床医生建立自己职业生涯所需的培训- 专注于临床遗传学和新生儿学交叉的研究人员走向更好的 了解婴儿死亡率并最终预防婴儿死亡率。

Project Summary/Abstract Genetic disorders and congenital malformations, which may be genetic, are the leading cause of infant mortality in the United States. However, we still do not fully understand which genetic disorders are responsible for infant deaths and the full scope of their impact. This NIH K23 research proposal represents a multidisciplinary effort to gain further understanding into the genetic contributions to infant mortality, leveraging the expertise that Dr. Wojcik has already gained through her dual training in clinical genetics and in neonatal-perinatal medicine and providing further training in genomic analysis, epidemiology and biostatistics, and clinical research study design. Building off of Dr. Wojcik's prior research on the implications of genetic diagnoses in the infant and neonatal period and her experience in exome analysis for novel disease gene discovery, the objective of this study is to determine the prevalence of Mendelian genetic disorders within a cohort of deceased infants (Aim 1) and to evaluate the public health impact of these diagnoses using parental survey data (Aim 2) and data obtained from the National Center for Health Statistics (Aim 3). Under the mentorship of internationally-recognized experts in neonatology and genomic medicine (Pankaj Agrawal, MD, MSSc), human genetics and rare disease gene discovery (Heidi Rehm, PhD), the ethical/legal/social implications of clinical genetics (Ingrid Holm, MD, MPH) and in collaboration with experts in parental grief after the loss of an infant (Richard Goldstein, MD), clinical genetics (Wen-Han Tann, MBBS), perinatal mortality/epidemiology (Dominique Heinke, ScD), with additional research and career mentoring from successful researchers in human genomics (Alan Beggs, PhD and Robert Green, MD, MPH), Dr. Wojcik will strive to provide answers to bereaved families. Concurrently, she will gain the training necessary to build her own career as an independent clinician- researcher with a focus on the intersection of clinical genetics and neonatology towards a better understanding of infant mortality and ultimately its prevention.