Although, the biological and medical value of identifying the genes and variants responsible for Mendelian disorders is extraordinarily high, the vast majority of these remain unexplained at the molecular level. To this end, we will create a partnership between two of the oldest and most accomplished human genetics programs in the country, those at Baylor College of Medicine (BCM) and Johns Hopkins University School of Medicine (JHUSOM), to form the Baylor-Hopkins Center for Mendelian Genomics (BHCMG). In doing so, we will take advantage of our complete access to OMIM and of the synergies afforded by combining our expertise in clinical genetics, genomic technologies, genetic analysis and understanding the biological basis of genetic disease. We will meet the challenge of finding and recruiting samples representing these rare disorders by creating and utilizing a worldwide network of colleagues and former trainees to identify and recruit thousands of patients and families with unexplained Mendelian phenotypes or with undiagnosed disease that segregates in their families as Mendelian traits. We already have >2,000 DNA samples in hand at our two institutions and have identified >12,000 DNA samples in our network of 17 collaborators around the world. Moreover, we have developed strategies to utilize OMIM (>10, 000 unique hits/day) to flag unexplained phenotypes and recruit samples. We will further organize our efforts by building a sample and disease-tracking database that is integrated with and accessible through OMIM as well as through a BHCMG web site and have assembled a committee of experts to assist with the inevitable ELSI issues. We will build on our existing high throughput genotyping and sequencing pipelines to develop an integrated laboratory effort and we will use a committee of experts from both institutions plus outside experts to analyze the data and develop new software tools to advance the field. Finally, to disseminate the phenotypic and molecular information we will follow an aggressive plan of data dissemination using OMIM and other web-based resources as well as organizing an annual Mendelian genetics meeting open to all.

Public Health Relevance

We will form a partnership between two distinguished programs in human genetics. The Baylor - Hopkins Center for Mendelian Genomics or BHCMG, to recruit samples from patients with Mendelian disorders. We will 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

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
1U54HG006542-01
Application #
8237388
Study Section
Special Emphasis Panel (ZHG1-HGR-P (O2))
Program Officer
Wang, Lu
Project Start
2011-12-05
Project End
2015-11-30
Budget Start
2011-12-05
Budget End
2012-11-30
Support Year
1
Fiscal Year
2012
Total Cost
$4,000,000
Indirect Cost
$529,269
Name
Johns Hopkins University
Department
None
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
James, Regis A; Campbell, Ian M; Chen, Edward S et al. (2016) A visual and curatorial approach to clinical variant prioritization and disease gene discovery in genome-wide diagnostics. Genome Med 8:13
Campbell, Ian M; Gambin, Tomasz; Jhangiani, Shalini N et al. (2016) Multiallelic Positions in the Human Genome: Challenges for Genetic Analyses. Hum Mutat 37:231-4
Yousaf, Sairah; Shahzad, Mohsin; Kausar, Tasleem et al. (2016) Identification and clinical characterization of Hermansky-Pudlak syndrome alleles in the Pakistani population. Pigment Cell Melanoma Res 29:231-5
Gomez-Ospina, Natalia; Potter, Carol J; Xiao, Rui et al. (2016) Mutations in the nuclear bile acid receptor FXR cause progressive familial intrahepatic cholestasis. Nat Commun 7:10713
Mirzaa, Ghayda M; Campbell, Catarina D; Solovieff, Nadia et al. (2016) Association of MTOR Mutations With Developmental Brain Disorders, Including Megalencephaly, Focal Cortical Dysplasia, and Pigmentary Mosaicism. JAMA Neurol 73:836-45
Iacovazzo, Donato; Caswell, Richard; Bunce, Benjamin et al. (2016) Germline or somatic GPR101 duplication leads to X-linked acrogigantism: a clinico-pathological and genetic study. Acta Neuropathol Commun 4:56
Ockeloen, Charlotte W; Khandelwal, Kriti D; Dreesen, Karoline et al. (2016) Novel mutations in LRP6 highlight the role of WNT signaling in tooth agenesis. Genet Med 18:1158-1162
Romere, Chase; Duerrschmid, Clemens; Bournat, Juan et al. (2016) Asprosin, a Fasting-Induced Glucogenic Protein Hormone. Cell 165:566-79
Gawlinski, Pawel; Posmyk, Renata; Gambin, Tomasz et al. (2016) PEHO Syndrome May Represent Phenotypic Expansion at the Severe End of the Early-Onset Encephalopathies. Pediatr Neurol 60:83-7
Carvalho, Claudia M B; Lupski, James R (2016) Mechanisms underlying structural variant formation in genomic disorders. Nat Rev Genet 17:224-38

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