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UW Center for Mendelian Genomics

威斯康星大学孟德尔基因组学中心

基本信息

批准号：
9922590
负责人：
MICHAEL Joseph BAMSHAD
金额：
$ 233.67万
依托单位：
UNIVERSITY OF WASHINGTON
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：
2019-04-29 至 2021-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9922590
关键词：
Adoption Adult Architecture Award Biological Assay Biological Models Childhood ClinVar Clinical Clinical Management Communities Complex Computing Methodologies Congenital Abnormality Congenital Heart Defects Copy Number Polymorphism Country Coupled Cystic Fibrosis Transmembrane Conductance Regulator DNA Data Deposition Development Diagnostic Diagnostic tests Disease Economic Burden England Epilepsy Evolution FURIN gene Family Funding Genes Genetic Genetic Medicine Genome Genomics Genotype Goals Gold Human Human Genetics Human Genome Individual Industry Infrastructure Institution Investigation Knowledge Leadership Link Methodology Methods Modeling Morbidity - disease rate Mutation National Heart, Lung, and Blood Institute National Human Genome Research Institute Ontology Open Reading Frames Parents Patients Penetrance Phase Phenotype Population Preventive Private Sector Process Production Public Sector RNA Splicing Rare Diseases Research Design Research Personnel Resources Risk Role Sampling Structure Sum Syndrome Technology Test Result Testing Therapeutic Time Translations Universities Untranslated RNA Variant Washington adjudicate analytical tool autism spectrum disorder base candidate validation causal variant clinical care clinical diagnostics clinical phenotype clinical practice cohort computerized tools cost cost effective data sharing database of Genotypes and Phenotypes developmental disease exome exome sequencing gene complementation gene discovery genome sequencing genomic data heuristics human disease improved industry partner innovation insertion/deletion mutation mortality new technology next generation sequencing novel novel strategies open data programs reproductive success technological innovation tool transcriptome sequencing treatment strategy variant of unknown significance whole genome

项目摘要

PROJECT SUMMARY/ABSTRACT (FROM FUNDED PARENT AWARD) To date, 2,937 genes underlying 4,163 Mendelian conditions (MCs) have been discovered. However, the genetic basis of over 3,000 MCs remains unknown, and hundreds of novel MCs are described each year. In 2011, the NHGRI and NHLBI established the Centers for Mendelian Genomics (CMG) to facilitate large-scale discovery of genes responsible for MCs. In Phase-1 of the CMG program, and in partnership with 182 investigators from 117 institutions in 27 countries, the University of Washington CMG (UW-CMG) assessed 6,598 samples from 2,404 families and has, to date, produced 4,116 exome and 97 whole genome sequences. This extensive collaborative effort resulted in an unparalleled pace of discovery with the identification of genes for 237 MCs, including 123 novel discoveries. The translation and impact of these discoveries on diagnostics and clinical care has been immediate and substantial—when combined with discoveries made by the genetics community at-large, variants in genes identified as underlying MCs since 2012 represent ~25% of positive results in clinical diagnostic efforts. Additionally, the UW-CMG has developed multiple new analytical tools including CADD, PRIMUS, SimRare, STAR, RV-TDT, CHP, VAT and Spliceosaurus as well as methodological innovations including MIPs, smMIPs and approaches for low input exome and genome sequencing. The UW- CMG remains deeply committed to open data sharing with rolling submission of eligible exome and genome data to dbGaP (614 deposited and 1,748 pending deposition) and development of a new data browser (http://geno2mp.gs.washington.edu) that, for the first time, publicly provides anonymized links between individual-level genotypes, from over 3,000 exomes, to individual clinical phenotypes, defined by Human Phenotype Ontology terms. In this renewal application, we build from these successes to maximize novel gene discovery for MCs, capitalizing on immediate access to >22,000 sequence-ready samples from >16,500 families and 163 MCs, access to several large cohorts of birth defects totaling more than 24,000 trios (>94,000 samples total) and an aggressive sample solicitation plan including case aggregation and case matching of undiagnosed patients who have undergone clinical exome sequencing. We propose four specific aims: (1) Solicit, organize, and curate phenotypic information and DNA samples from families with unexplained (i.e., no known underlying gene) MCs from sample custodians around the world, by submission to our center of either samples for sequencing or sequence data for further analysis; (2) Apply our established production pipeline for exome and genome sequencing to samples corresponding to unexplained MCs and to improve this process through ongoing technology innovation; (3) Determine the genetic basis of as many unexplained MCs as is possible, maximizing novel discovery, by use of efficient study design and effective, innovative analysis; (4) Take a leadership role to disseminate and openly share methods and data to promote worldwide efforts to discover the full complement of genes underlying MCs.

项目摘要/摘要（来自资助家长奖）

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A new NBIA patient from Turkey with homozygous C19ORF12 mutation.

一名来自土耳其的新 NBIA 患者，具有 C19ORF12 纯合突变。

DOI：
10.1007/s13760-018-1026-5
发表时间：
2019
期刊：
Acta neurologica Belgica
影响因子：
2.7
作者：
Kasapkara,ÇiğdemSeher;Tümer,Leyla;Gregory,Allison;Ezgü,Fatih;İnci,Aslı;Derinkuyu,BetülEmine;Fox,Rachel;Rogers,Caleb;Hayflick,Susan
通讯作者：
Hayflick,Susan

Mutations in IFT-A satellite core component genes IFT43 and IFT121 produce short rib polydactyly syndrome with distinctive campomelia.

DOI：
10.1186/s13630-017-0051-y
发表时间：
2017-01-01
期刊：
Cilia
影响因子：
0
作者：
Duran, Ivan;Taylor, S Paige;Krakow, Deborah
通讯作者：
Krakow, Deborah

A disease-causing novel missense mutation in the ST14 gene underlies autosomal recessive ichthyosis with hypotrichosis syndrome in a consanguineous family.

DOI：
10.1684/ejd.2017.3210
发表时间：
2018-04-01
期刊：
European journal of dermatology : EJD
影响因子：
0
作者：
Ahmad F;Ahmed I;Nasir A;Umair M;Shahzad S;Muhammad D;Santos-Cortez RLP;Leal SM;Ahmad W
通讯作者：
Ahmad W

A novel homozygous variant in BMPR1B underlies acromesomelic dysplasia Hunter-Thompson type.