Abstract

OF PARENT AWARD: In its 7th year of funding, the Baylor-Hopkins Center for Mendelian Genomics (BHCMG) aims to identify high penetrance variants causing Mendelian phenotypes in all the protein-coding genes in the human genome. To this end we have recruited samples from > 70 countries around the globe and used whole exome sequencing (WES) coupled with whole genome SNP arrays to search for the responsible genes and causative variants. Currently, we have studied >550 phenotypes and performed ~10,000 exomes and identified 107 novel Tier 1 genes and 251 Tier 2 genes. To facilitate this effort, we have developed and utilized PhenoDB, GeneMatcher and a variety of other software tools. Our results have been disseminated in 218 publications and by distribution of data in ClinVar and dbGaP.

Public Health Relevance

We have formed a partnership between two distinguished programs in human genetics, The Baylor ? Hopkins Center for Mendelian Genomics or BHCMG, to recruit patients with Mendelian disorders. We continue to use state of the art genetics and genomics technology and analyses to identify the genes and variants responsible for these disorders and disseminate our results to the biomedical community.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Research Project with Complex Structure Cooperative Agreement (UM1)
Project #
3UM1HG006542-07S1
Application #
9698731
Study Section
Program Officer
Wellington, Christopher
Project Start
2011-12-05
Project End
2018-11-30
Budget Start
2018-07-01
Budget End
2018-11-30
Support Year
7
Fiscal Year
2018
Total Cost
Indirect Cost

  Institution

Name
Johns Hopkins University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205

  Publications

Cheng, Hanyin; Dharmadhikari, Avinash V; Varland, Sylvia et al. (2018) Truncating Variants in NAA15 Are Associated with Variable Levels of Intellectual Disability, Autism Spectrum Disorder, and Congenital Anomalies. Am J Hum Genet 102:985-994
White, Janson J; Mazzeu, Juliana F; Coban-Akdemir, Zeynep et al. (2018) WNT Signaling Perturbations Underlie the Genetic Heterogeneity of Robinow Syndrome. Am J Hum Genet 102:27-43
Poli, M Cecilia; Ebstein, Frédéric; Nicholas, Sarah K et al. (2018) Heterozygous Truncating Variants in POMP Escape Nonsense-Mediated Decay and Cause a Unique Immune Dysregulatory Syndrome. Am J Hum Genet 102:1126-1142
Wiszniewski, Wojciech; Gawlinski, Pawel; Gambin, Tomasz et al. (2018) Comprehensive genomic analysis of patients with disorders of cerebral cortical development. Eur J Hum Genet 26:1121-1131
Coban-Akdemir, Zeynep; White, Janson J; Song, Xiaofei et al. (2018) Identifying Genes Whose Mutant Transcripts Cause Dominant Disease Traits by Potential Gain-of-Function Alleles. Am J Hum Genet 103:171-187
Chinn, Ivan K; Eckstein, Olive S; Peckham-Gregory, Erin C et al. (2018) Genetic and mechanistic diversity in pediatric hemophagocytic lymphohistiocytosis. Blood 132:89-100
Konno, Hiroyasu; Chinn, Ivan K; Hong, Diana et al. (2018) Pro-inflammation Associated with a Gain-of-Function Mutation (R284S) in the Innate Immune Sensor STING. Cell Rep 23:1112-1123
Jordan, Valerie K; Beck, Tyler F; Hernandez-Garcia, Andres et al. (2018) The role of FREM2 and FRAS1 in the development of congenital diaphragmatic hernia. Hum Mol Genet 27:2064-2075
Wang, Xia; Posey, Jennifer E; Rosenfeld, Jill A et al. (2018) Phenotypic expansion in DDX3X - a common cause of intellectual disability in females. Ann Clin Transl Neurol 5:1277-1285
Du, Renqian; Dinckan, Nuriye; Song, Xiaofei et al. (2018) Identification of likely pathogenic and known variants in TSPEAR, LAMB3, BCOR, and WNT10A in four Turkish families with tooth agenesis. Hum Genet 137:689-703

Showing the most recent 10 out of 90 publications