title: Disrupted human-pathogen co-evolution: a model for disease.
abstract: A major goal in infectious disease research is to identify the human and pathogenic genetic variants that explain differences in microbial pathogenesis. However, neither pathogenic strain nor human genetic variation in isolation has proven adequate to explain the heterogeneity of disease pathology. We suggest that disrupted co-evolution between a pathogen and its human host can explain variation in disease outcomes, and that genome-by-genome interactions should therefore be incorporated into genetic models of disease caused by infectious agents. Genetic epidemiological studies that fail to take both the pathogen and host into account can lead to false and misleading conclusions about disease etiology. We discuss our model in the context of three pathogens, Helicobacter pylori, Mycobacterium tuberculosis and human papillomavirus, and generalize the conditions under which it may be applicable.
authors.affiliation: Department of Genetics, Geisel School of Medicine, Dartmouth College Hanover, NH, USA ; Department of Molecular Physiology and Biophysics, Center for Human Genetics Research, Vanderbilt University Medical Center Nashville, TN, USA.
authors.forename: Nuri
authors.initials: N
authors.lastname: Kodaman
authors.affiliation: Department of Genetics, Geisel School of Medicine, Dartmouth College Hanover, NH, USA ; Department of Molecular Physiology and Biophysics, Center for Human Genetics Research, Vanderbilt University Medical Center Nashville, TN, USA.
authors.forename: Rafal S
authors.initials: RS
authors.lastname: Sobota
authors.affiliation: Division of Gastroenterology, Department of Medicine, Vanderbilt University Medical Center Nashville, TN, USA.
authors.forename: Robertino
authors.initials: R
authors.lastname: Mera
authors.affiliation: Division of Gastroenterology, Department of Medicine, Vanderbilt University Medical Center Nashville, TN, USA.
authors.forename: Barbara G
authors.initials: BG
authors.lastname: Schneider
authors.affiliation: Department of Genetics, Geisel School of Medicine, Dartmouth College Hanover, NH, USA.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Williams
keywords: Helicobacter pylori; Mycobacterium tuberculosis; genome–genome interactions; host–pathogen co-evolution; human disease; human papillomavirus