Jean-Laurent Casanova (The Rockefeller University)

Toward a genetic theory of childhood infectious diseases
Date
Jan 31, 2018, 12:00 pm1:00 pm
Location
Thomas Laboratory, 003
Audience
Free and open to the university community and the public.

Speakers

Jean-Laurent Casanova, M.D., Ph.D.
Professor
Investigator, Howard Hughes Medical Institute Head
St. Giles Laboratory of Human Genetics of Infectious Diseases, Senior Attending Physician
Rockefeller University
Howard Hughes Medical Insitute

Details

Event Description

The hypothesis that inborn errors of immunity underlie infectious diseases is gaining experimental support. However, the apparent modes of inheritance of predisposition or resistance differ considerably between diseases and between studies. A coherent genetic architecture of infectious diseases is lacking. We suggest here that life-threatening infectious diseases in childhood, occurring in the course of primary infection, result mostly from individually rare but collectively diverse single-gene variations of variable clinical penetrance, whereas the genetic component of predisposition to secondary or reactivation infections in adults is more complex. This model is consistent with (i) the high incidence of most infectious diseases in early childhood, followed by a steady decline, (ii) theoretical modeling of the impact of monogenic or polygenic predisposition on the incidence distribution of infectious diseases before reproductive age, (iii) available molecular evidence from both monogenic and complex genetics of infectious diseases in children and adults, (iv) current knowledge of immunity to primary and secondary or latent infections, (v) the state of the art in the clinical genetics of non-infectious pediatric and adult diseases, and (vi) evolutionary data for the genes underlying single-gene and complex disease risk. With the recent advent of new-generation deep resequencing, this model of single-gene variations underlying severe pediatric infectious diseases is experimentally testable.

Sponsor
Alex Ploss, Department of Molecular Biology
Event Category
Butler Seminar Series