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Yale Center for Mendelian Genomics

耶鲁大学孟德尔基因组学中心

基本信息

批准号：
10037978
负责人：
MURAT GUNEL
金额：
$ 242.55万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-12-05 至 2021-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10037978
关键词：
Automated Annotation Biology Cells Code Collaborations Communities Complex Congenital Abnormality Coupled Data Deposition Detection Development Diagnosis Diagnostic Disease Dominant Genetic Conditions Endocrine Family Genes Genetic Genome Genomics Goals Hand Health Heart Heterogeneity Hormones Human Individual Industry Standard Institution International Journals Kidney Knock-out Knowledge Libraries Link Maps Medicine Mendelian disorder Methods Modeling Mutation Nature Neurons New England Open Reading Frames Paper Pathway interactions Patients Penetrance Phenotype Phylogeny Physicians Population Preparation Production Proteins Publications Reagent Research Research Design Research Personnel Sampling Science Signal Transduction Somatic Mutation Talents Technology Testing Therapeutic Time Variant Work analytical method base biliary tract body system brain malformation case control clinical Diagnosis clinical sequencing cohort cost cost effective data sharing database of Genotypes and Phenotypes de novo mutation disease-causing mutation disorder risk exome exome sequencing experience flexibility gene discovery genome sequencing genome-wide genomic variation interest loss of function meetings next generation pre-clinical programs public health relevance recessive genetic trait recruit sequencing platform skills success technology development therapeutic target tool trait tumor whole genome

项目摘要

DESCRIPTION (provided by applicant): This is a renewal application for the Yale Center for Mendelian Genomics. The biology linking Mendelian mutations to traits has transformed our understanding of every organ system, identifying therapeutic targets, and allowing preclinical diagnosis and mitigation of disease risk. We know the consequence of mutation of fewer than 3,000 genes. With ~19,000 protein-coding genes, the vast majority of which are conserved across phylogeny, even allowing for 30% lethality, there are doubtless thousands of Mendelian loci awaiting discovery. The full utility of clinical sequencing will not be realized without bette understanding of the consequence of mutation of every gene. The advent of robust exome and genome sequencing allows unprecedented opportunity for discovery of new Mendelian trait loci. In the current cycle, by sequencing more than 7000 exomes from investigators world-wide we have identified 180 new Mendelian trait loci with high confidence, 35 phenotypic expansions, and hundreds more that are likely new trait loci across a range of traits and genetic mechanisms, including de novo mutations, incomplete penetrance, and complex rare recessive traits. Several new loci have immediate therapeutic implications. These results underscore that many new trait loci remain to be described and solved, motivating efforts to complete the human `knock out' map. We now propose, by building upon the current studies and through reduction in high quality exome cost to $330, to identify at least another 500 trait loci via the sequencing of more than 20,000 samples, advancing the understanding of genomes, health and disease.

描述（由申请人提供）：这是耶鲁大学孟德尔基因组学中心的更新申请。将孟德尔突变与性状联系起来的生物学改变了我们对每个器官系统的理解，确定了治疗靶点，并允许临床前诊断和减轻疾病风险。我们知道少于3,000个基因突变的后果。大约有19，000个蛋白质编码基因，其中绝大多数在遗传学上是保守的，甚至允许30%的致死率，毫无疑问，有数千个孟德尔基因座等待发现。如果不能更好地了解每一个基因突变的后果，就不能充分发挥临床测序的作用。强大的外显子组和基因组测序的出现为发现新的孟德尔性状基因座提供了前所未有的机会。在当前的周期中，通过对来自世界各地研究人员的7000多个外显子组进行测序，我们已经确定了180个新的孟德尔性状基因座，具有高置信度，35个表型扩展，以及数百个可能是一系列性状和遗传机制的新性状基因座，包括从头突变，不完全突变和复杂的罕见隐性性状。几个新的基因座具有直接的治疗意义。这些结果强调，许多新的性状基因座仍有待描述和解决，激励努力完成人类的'敲除'地图。我们现在建议，通过建立在目前的研究和通过降低高质量的外显子组成本到330美元，通过超过20，000个样本的测序确定至少另外500个性状基因座，推进对基因组，健康和疾病的理解。

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）

Further delineation of familial polycystic ovary syndrome (PCOS) via whole-exome sequencing: PCOS-related rare FBN3 and FN1 gene variants are identified.

DOI：
10.1111/jog.15187
发表时间：
2022-05
期刊：
The journal of obstetrics and gynaecology research
影响因子：
0
作者：
通讯作者：

Genetic Influence on Neurodevelopment in Nonsyndromic Craniosynostosis.

DOI：
10.1097/prs.0000000000008976
发表时间：
2022-05-01
期刊：
Plastic and reconstructive surgery
影响因子：
3.6
作者：
通讯作者：

Dual activating FGFR1 mutations in pediatric pilomyxoid astrocytoma.

DOI：
10.1002/mgg3.1597
发表时间：
2021-03
期刊：
Molecular genetics & genomic medicine
影响因子：
2
作者：
Fomchenko EI;Reeves BC;Sullivan W;Marks AM;Huttner A;Kahle KT;Erson-Omay EZ
通讯作者：
Erson-Omay EZ

Biallelic PRMT7 pathogenic variants are associated with a recognizable syndromic neurodevelopmental disorder with short stature, obesity, and craniofacial and digital abnormalities.

DOI：
10.1016/j.gim.2022.09.016
发表时间：
2023-01
期刊：
GENETICS IN MEDICINE
影响因子：
8.8
作者：
Cali, Elisa;Suri, Mohnish;Scala, Marcello;Ferla, Matteo P.;Alavi, Shahryar;Faqeih, Eissa Ali;Bijlsma, Emilia K.;Wigby, Kristen M.;Baralle, Diana;Mehrjardi, Mohammad Y., V;Schwab, Jennifer;Platzer, Konrad;Steindl, Katharina;Hashem, Mais;Jones, Marilyn;Niyazov, Dmitriy M.;Jacober, Jennifer;Littlejohn, Rebecca Okashah;Weis, Denisa;Zadeh, Neda;Rodan, Lance;Goldenberg, Alice;Lecoquierre, Francois;Dutra-Clarke, Marina;Horvath, Gabriella;Young, Dana;Orenstein, Naama;Bawazeer, Shahad;Vulto-van Silfhout, Anneke T.;Herenger, Yvan;Dehghani, Mohammadreza;Seyedhassani, Seyed Mohammad;Bahreini, Amir;Nasab, Mahya E.;Ercan-Sencicek, A. Gulhan;Firoozfar, Zahra;Movahedinia, Mojtaba;Efthymiou, Stephanie;Striano, Pasquale;Karimiani, Ehsan Ghayoor;Salpietro, Vincenzo;Taylor, Jenny C.;Redman, Melody;Stegmann, Alexander P. A.;Laner, Andreas;Abdel-Salam, Ghada;Li, Megan;Bengala, Mario;Muller, Amelie Johanna;Digilio, Maria C.;Rauch, Anita;Gunel, Murat;Titheradge, Hannah;Schweitzer, Daniela N.;Kraus, Alison;Valenzuela, Irene;McLean, Scott D.;Phornphutkul, Chanika;Salih, Mustafa;Begtrup, Amber;Schnur, Rhonda E.;Torti, Erin;Haack, Tobias B.;Prada, Carlos E.;Alkuraya, Fowzan S.;Houlden, Henry;Maroofian, Reza
通讯作者：
Maroofian, Reza

A rare etiology of tetralogy of Fallot with pulmonary atresia: Renpenning syndrome.