The biomedical value of identifying the genes and variants responsible for Mendelian disorders is extraordinarily high. The clinical manifestations of these disorders involve virtually all organ systems and their developmental and physiological parameters. About half of recognized Mendelian disorders (as enumerated in the OMIM database) remain unexplained at the molecular level and many more of these remain to be recognized. Over the last 3.25 years, the Baylor College of Medicine and the Johns Hopkins University School of Medicine human genetics programs have combined and formed the Baylor-Hopkins Center for Mendelian Genomics (BHCMG) to find Mendelian genes. In doing so, we have taken advantage of the synergies afforded by combining our expertise in clinical genetics, genomic technologies, genetic analysis and understanding the biological basis of genetic disease. We have met and will continue to meet the challenge of research subjects by utilizing our worldwide network of colleagues and former trainees. Using state of the art genomic methods and analytic tools, we have already sequenced the exome or the genome of 5,443 individuals, identifying 169 novel disease genes in the first 3.25 years of funding, and have more than 4,000 samples ready to sequence from collaborators in the USA and >20 other countries. In the future, we will expand this network of collaborators to identify even more samples. We have also developed automated processes to contact the authors of publications from unexplained Mendelian disorders in OMIM to recruit additional specific disease examples. We have designed and passed through the IRB an online consenting process that bypasses the bottlenecks of time difference and language in international and remote site recruiting. To streamline and monitor our progress we have developed PhenoDB, a web-based tool for the collection, storage and analysis of disease, phenotypic feature and genotype information. PhenoDB also tracks samples, and is updated with the deliberations of our expert committees for Phenotype Review and ELSI issues. We have and will continue to build on our existing high throughput sequencing pipelines and have developed integrated laboratory and analysis efforts with experts from both institutions to develop new methods and software to advance the field. We have and will disseminate the phenotype and molecular information through publication, lectures, posting to communal websites and dbGaP. To connect clinicians and scientists with interest in the same gene and accelerate confirmation of novel disease gene identification, we developed GeneMatcher, now part of the MatchMaker Exchange initiative involving geneticists around the world. Going forward, to educate health care providers and trainees, we plan to develop a Massive Open Online Course in genetics, and to educate the public while enhancing recruitment, we will develop a set of online educational videos.

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.

National Institute of Health (NIH)
National Human Genome Research Institute (NHGRI)
Research Project with Complex Structure Cooperative Agreement (UM1)
Project #
Application #
Study Section
Special Emphasis Panel (ZHG1)
Program Officer
Wang, Lu
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Johns Hopkins University
Schools of Medicine
United States
Zip Code
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
Nilsson, Daniel; Pettersson, Maria; Gustavsson, Peter et al. (2016) Whole-Genome Sequencing of Cytogenetically Balanced Chromosome Translocations Identifies Potentially Pathological Gene Disruptions and Highlights the Importance of Microhomology in the Mechanism of Formation. Hum Mutat :
Stray-Pedersen, Asbjørg; Sorte, Hanne Sørmo; Samarakoon, Pubudu et al. (2016) Primary immunodeficiency diseases: Genomic approaches delineate heterogeneous Mendelian disorders. J Allergy Clin Immunol :
Hanchard, Neil A; Swaminathan, Shanker; Bucasas, Kristine et al. (2016) A genome-wide association study of congenital cardiovascular left-sided lesions shows association with a locus on chromosome 20. Hum Mol Genet 25:2331-2341
Fieremans, Nathalie; Van Esch, Hilde; Holvoet, Maureen et al. (2016) Identification of Intellectual Disability Genes in Female Patients with a Skewed X-Inactivation Pattern. Hum Mutat 37:804-11
Lindstrand, Anna; Frangakis, Stephan; Carvalho, Claudia M B et al. (2016) Copy-Number Variation Contributes to the Mutational Load of Bardet-Biedl Syndrome. Am J Hum Genet 99:318-36
White, Janson; Beck, Christine R; Harel, Tamar et al. (2016) POGZ truncating alleles cause syndromic intellectual disability. Genome Med 8:3
Szafranski, Przemyslaw; Gambin, Tomasz; Dharmadhikari, Avinash V et al. (2016) Pathogenetics of alveolar capillary dysplasia with misalignment of pulmonary veins. Hum Genet 135:569-86
Yuan, Bo; Neira, Juanita; Gu, Shen et al. (2016) Nonrecurrent PMP22-RAI1 contiguous gene deletions arise from replication-based mechanisms and result in Smith-Magenis syndrome with evident peripheral neuropathy. Hum Genet 135:1161-74
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

Showing the most recent 10 out of 32 publications