A genotype-first approach to defining the subtypes of a complex disease

Holly A Stessman; Raphael Bernier; Evan E Eichler

doi:10.1016/j.cell.2014.02.002

A genotype-first approach to defining the subtypes of a complex disease

Cell. 2014 Feb 27;156(5):872-7. doi: 10.1016/j.cell.2014.02.002.

Authors

Holly A Stessman¹, Raphael Bernier², Evan E Eichler³

Affiliations

¹ Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
² Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA 98195, USA.
³ Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA; Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA. Electronic address: eee@gs.washington.edu.

Abstract

Medical genetics typically entails the detailed characterization of a patient's phenotypes followed by genotyping to discover the responsible gene or mutation. Here, we propose that the systematic discovery of genetic variants associated with complex diseases such as autism are progressing to a point where a reverse strategy may be fruitful in assigning the pathogenic effects of many different genes and in determining whether particular genotypes manifest as clinically recognizable phenotypes. This "genotype-first" approach for complex disease necessitates the development of large, highly integrated networks of researchers, clinicians, and patient families, with the promise of improved therapies for subsets of patients.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Autistic Disorder / classification
Autistic Disorder / diagnosis
Autistic Disorder / genetics*
Community Networks
Exome
Genetic Heterogeneity*
Genotype*
Humans
Mutation
Phenotype

Abstract

Publication types

MeSH terms

Grants and funding