Over the years, our laboratory has made significant and fundamental contributions to the understanding of Hirschsprung disease (HSCR), and we continue to do so through a currently funded MERIT award that focuses on gene discovery using genetics and genomics. Nevertheless, our research is severely hampered by small sample sizes, non-representative patient recruitment, incomplete phenotypic/clinical data, and difficulties in obtaining access to tissues, since most cases are self-referrals. As we advance from the genetic epidemiological and molecular descriptions of HSCR to potential clinical applications, we will require larger numbers of extensively phenotyped representative patients with corresponding tissue samples. To enable this transition for the HSCR basic and clinical research communities, we are proposing a supplement to the currently funded award to expand our fourth aim of data and sample collection. We have recently formed the Hirschsprung Disease Research Collaborative (HDRC), an organization of geneticists, pediatric surgeons, pathologists and gastroenterologists to capitalize on HDRC members'areas of expertise, and direct patient access, to create a phenotype-genotype-tissue resource.
Our specific aims for this revision are: (1) to increase patient sample size and diversity for genomic studies;(2) to collect standardized phenotype data under uniform protocols;and, (3) to develop a high quality collaborative phenotype and tissue repository. The overall goal of this proposal is to build and maintain a well-documented resource, open to all HDRC members, that will not only improve our ability to use modern genomic techniques to carry out the existing aims of the MERIT award, but to further advance fundamental understanding of HSCR through an intellectual and resource collaboration of diverse experts in the field.

Public Health Relevance

Current research on Hirschsprung disease (HSCR) is severely hampered by small sample sizes, non-representative patient recruitment, incomplete phenotypic/clinical data, and difficulties in obtaining tissues. We intend to remove these impediments through the recently formed Hirschsprung Disease Research Collaborative (HDRC), an organization of geneticists, pediatric surgeons, pathologists and gastroenterologists to capitalize on HDRC members'areas of expertise and direct patient access to create a phenotype-genotype- tissue resource of uniformly collected data on large samples of representative HSCR patients. To enable basic and clinical research impacting on patient care and outcome, we are proposing a supplement to the currently funded MERIT award to expand our fourth aim of data and sample collection through the HDRC.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
3R37HD028088-20S1
Application #
8504484
Study Section
Genetics of Health and Disease Study Section (GHD)
Program Officer
Henken, Deborah B
Project Start
1991-04-01
Project End
2015-03-31
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
20
Fiscal Year
2013
Total Cost
$82,226
Indirect Cost
$31,469
Name
Johns Hopkins University
Department
Genetics
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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Jannot, Anne-Sophie; Pelet, Anna; Henrion-Caude, Alexandra et al. (2013) Chromosome 21 scan in Down syndrome reveals DSCAM as a predisposing locus in Hirschsprung disease. PLoS One 8:e62519
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Jiang, Qian; Ho, Yen-Yi; Hao, Li et al. (2011) Copy number variants in candidate genes are genetic modifiers of Hirschsprung disease. PLoS One 6:e21219
Emison, Eileen Sproat; Garcia-Barcelo, Merce; Grice, Elizabeth A et al. (2010) Differential contributions of rare and common, coding and noncoding Ret mutations to multifactorial Hirschsprung disease liability. Am J Hum Genet 87:60-74