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

Callaway, Danielle A; Campbell, Ian M; Stover, Samantha R et al. (2018) Prioritization of Candidate Genes for Congenital Diaphragmatic Hernia in a Critical Region on Chromosome 4p16 using a Machine-Learning Algorithm. J Pediatr Genet 7:164-173
Wang, Kun; Zhao, Sen; Liu, Bowen et al. (2018) Perturbations of BMP/TGF-? and VEGF/VEGFR signalling pathways in non-syndromic sporadic brain arteriovenous malformations (BAVM). J Med Genet 55:675-684
Dinckan, Nuriye; Du, Renqian; Akdemir, Zeynep C et al. (2018) A biallelic ANTXR1 variant expands the anthrax toxin receptor associated phenotype to tooth agenesis. Am J Med Genet A 176:1015-1022
Punetha, Jaya; Mackay-Loder, Loren; Harel, Tamar et al. (2018) Identification of a pathogenic PMP2 variant in a multi-generational family with CMT type 1: Clinical gene panels versus genome-wide approaches to molecular diagnosis. Mol Genet Metab 125:302-304
Karaca, Ender; Posey, Jennifer E; Coban Akdemir, Zeynep et al. (2018) Phenotypic expansion illuminates multilocus pathogenic variation. Genet Med :
Jiang, Yunyun; Wangler, Michael F; McGuire, Amy L et al. (2018) The phenotypic spectrum of Xia-Gibbs syndrome. Am J Med Genet A 176:1315-1326
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

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