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Nature and contribution of noncoding, regulatory mutations in neurodevelopmental disorders

神经发育障碍中非编码调节突变的性质和贡献

基本信息

批准号：
10200646
负责人：
Tychele Naomi Turner
金额：
$ 24.65万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-01 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10200646
关键词：
Address Advisory Committees Affect Algorithms Animal Model Architecture Area Award Bachelor&apos s Degree Basic Science Biological Assay Brain Caliber Cells Cellular Assay Chromatin Collaborations Complex Consent Coupled DNA Data Data Set Databases Development Disease Doctor of Philosophy Drosophila melanogaster Embryo Enhancers Etiology Family Funding Future Genetic Genetic Diseases Genome Genomics Genotype Goals Human Human Genetics In Vitro Individual Inherited Knowledge Laboratories Mentors Methods Michigan Molecular Biology Molecular Genetics Mouse Cell Line Mus Mutation Nature Neurodevelopmental Disorder Neurons Nucleic Acid Regulatory Sequences Other Genetics Pathway interactions Population Population Genetics Privatization Regulation Reporter Research Research Personnel Resolution Role Running Scientist Single Nucleotide Polymorphism Sister Site Structure Supervision Techniques Technology Testing Therapeutic Time Tissues Training Training Programs Transposase Universities Untranslated RNA Variant Washington Work base exome exome sequencing genetic architecture genetic risk factor genome sciences genome sequencing genomic variation improved in vitro testing in vivo in vivo evaluation insertion/deletion mutation insight medical schools mouse development novel promoter skills variant detection whole genome

项目摘要

Project Summary This proposal for a Pathway to Independence Award focuses on the training of Dr. Tychele Turner to become an independent investigator of large-scale genomics and human genetics. Dr. Turner has a Bachelor's Degree from Michigan State University in Genomics and Molecular Genetics and a Ph.D. in Human Genetics and Molecular Biology from the Johns Hopkins University School of Medicine. Proposed studies will advance her genomics training into long-read based technologies and massively parallel reporter assays (MPRAs) to assess function of variants discovered in genomes from individuals with neurodevelopmental disorders (NDDs). Another essential piece will be the development of a collaboration for assessing function of these variants in vivo. The training program will consist of two years of mentored training in the laboratory of Dr. Evan Eichler and three years of funding for her independent laboratory. Specifically, the training program will center on the study of noncoding variants in NDDs by identifying these variants and assessing their function. The mentored work will take place under the supervision of the primary mentor, Dr. Evan Eichler, and the co-mentor, Dr. Jay Shendure, both at the University of Washington (UW) Department of Genome Sciences (GS). Both the mentor and co-mentor are well-established experts in the characterization of genomes and high-throughput functional assays of genomic variation, respectively. Dr. Turner will also gain advice from a formal advisory committee as well as through activities arranged by the Department of GS. This department is an optimal place for the mentored training providing the candidate with access to a number of high caliber scientists in areas ranging from basic science, model organisms, disease genomics, population genetics, development and high throughput functional assessment of genomes. While there has been considerable progress in our understanding of the genetics of NDDs through the use of exome and array technologies there still remains an appreciable gap in understanding of their genetic architecture. In proposed studies, we will assess NDDs via a genome-first strategy coupled with functional- based assays to determine the role of noncoding variation in NDDs. We will approach this by (1) calling and statistical assessment of variants from whole-genome sequencing data in 14,000 families; (2) variant prioritization via single-cell based assays identifying regulatory sites in the brain; and (3) by MPRAs of variant function coupled with in vivo functional characterization of a subset of these variants in mice. The skills learned in this proposal are on the cutting-edge and many are unique to the setting of the UW Department of GS. The candidate will amass a great amount of knowledge in new areas of genomics, which will be applicable to many diseases and critical to the candidate's future independent laboratory.

项目总结

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

de novo variant calling identifies cancer mutation signatures in the 1000 Genomes Project.

DOI：
10.1002/humu.24455
发表时间：
2022-12
期刊：
HUMAN MUTATION
影响因子：
3.9
作者：
Ng, Jeffrey K.;Vats, Pankaj;Fritz-Waters, Elyn;Sarkar, Stephanie;Sams, Eleanor I.;Padhi, Evin M.;Payne, Zachary L.;Leonard, Shawn;West, Marc A.;Prince, Chandler;Trani, Lee;Jansen, Marshall;Vacek, George;Samadi, Mehrzad;Harkins, Timothy T.;Pohl, Craig;Turner, Tychele N.
通讯作者：
Turner, Tychele N.

HAT: de novo variant calling for highly accurate short-read and long-read sequencing data.

HAT：从头变体调用，需要高度准确的短读长和长读长测序数据。