The Burden of Genetic Disorders in Infant Mortality

项目总结/摘要 遗传性疾病和先天性畸形，可能是遗传性的，是主要原因 美国婴儿死亡率的一半。然而，我们仍然不完全了解哪些基因 疾病是造成婴儿死亡及其全面影响的原因。关于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Wojcik博士已经掌握的专业知识， 通过她在临床遗传学和围产期医学方面的双重培训获得， 提供基因组分析、流行病学和生物统计学以及临床 研究设计。基于Wojcik博士先前对遗传影响的研究， 在婴儿和新生儿期的诊断和她的经验，外显子组分析的新的 疾病基因的发现，本研究的目的是确定孟德尔的患病率 死亡婴儿队列中的遗传性疾病（目标1），并评估公共卫生 使用父母调查数据（目标2）和从 国家卫生统计中心（目标3）。在国际知名的 遗传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（海蒂雷姆，博士），伦理/法律的/社会影响， 临床遗传学（Ingrid霍尔姆，医学博士，公共卫生硕士），并与专家合作，在父母的悲痛后， 婴儿死亡（Richard Goldstein，医学博士），临床遗传学（Wen-Han Tann，MBBS）， 围产期死亡率/流行病学（多米尼克海因克，ScD），与其他研究和职业 来自人类基因组学成功研究人员的指导（Alan Beggs博士和Robert 绿色，医学博士，公共卫生硕士），沃伊奇克博士将努力提供答案，以失去亲人的家庭。与此同时， 她将获得必要的培训，以建立自己的职业生涯作为一个独立的临床医生- 研究人员，专注于临床遗传学和生殖学的交叉，以更好地 了解婴儿死亡率并最终预防其发生。

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.