Defining Disease, Diagnosis, and Translational Medicine within a Homeostatic Perturbation Paradigm: The National Institutes of Health Undiagnosed Diseases Program Experience.
Document Type
Article
Publication Date
5-26-2017
JAX Source
Front Med (Lausanne) 2017 May 26; 4:62.
Volume
4
First Page
62
Last Page
62
PMID
28603714
Grant
HG000215-07
Abstract
Traditionally, the use of genomic information for personalized medical decisions relies on prior discovery and validation of genotype-phenotype associations. This approach constrains care for patients presenting with undescribed problems. The National Institutes of Health (NIH) Undiagnosed Diseases Program (UDP) hypothesized that defining disease as maladaptation to an ecological niche allows delineation of a logical framework to diagnose and evaluate such patients. Herein, we present the philosophical bases, methodologies, and processes implemented by the NIH UDP. The NIH UDP incorporated use of the Human Phenotype Ontology, developed a genomic alignment strategy cognizant of parental genotypes, pursued agnostic biochemical analyses, implemented functional validation, and established virtual villages of global experts. This systematic approach provided a foundation for the diagnostic or non-diagnostic answers provided to patients and serves as a paradigm for scalable translational research. Front Med (Lausanne) 2017 May 26; 4:62.
Recommended Citation
Gall T,
Valkanas E,
Bello C,
Markello T,
Adams C,
Bone W,
Brandt A,
Brazill J,
Carmichael L,
Davids M,
Davis J,
Diaz-Perez Z,
Draper D,
Elson J,
Flynn E,
Godfrey R,
Groden C,
Hsieh C,
Fischer R,
Golas G,
Guzman J,
Huang Y,
Kane M,
Lee E,
Li C,
Links A,
Maduro V,
Malicdan M,
Malik F,
Nehrebecky M,
Park J,
Pemberton P,
Schaffer K,
Simeonov D,
Sincan M,
Smedley D,
Valivullah Z,
Wahl C,
Washington N,
Wolfe L,
Xu K,
Zhu Y,
Gahl W,
Tifft C,
Toro C,
Adams D,
He M,
Robinson P,
Haendel M,
Zhai R,
Boerkoel C.
Defining Disease, Diagnosis, and Translational Medicine within a Homeostatic Perturbation Paradigm: The National Institutes of Health Undiagnosed Diseases Program Experience. Front Med (Lausanne) 2017 May 26; 4:62.