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Chapter 7 - Functional validation of candidate genetic susceptibility factors for major mental illnesses

From protein chemistry, cell biology, and animal studies, to human brain imaging

Published online by Cambridge University Press:  05 October 2012

By
Akira Sawa ,
Wanli W. Smith ,
Saurav Seshadri ,
Akiko Hayashi-Takagi ,
Hanna Jaaro-Peled  and
Atsushi Kamiya
Edited by
John I. Nurnberger, Jr  and
Wade Berrettini
John I. Nurnberger, Jr
Affiliation:
Indiana University School of Medicine
Wade Berrettini
Affiliation:
University of Pennsylvania School of Medicine
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Summary

This chapter reviews how functions of genetic susceptibility factors can be validated, specifically using disrupted in schizophrenia 1 (DISC1) as an example. Studies at multiple levels, from protein chemistry, cell biology, animal study, to clinical work provide comprehensive understanding of the functions of susceptibility factors. Once genetic studies identify candidate susceptibility factors for the diseases, functions of such proteins can be tested in cells by modulating expression of the target molecules or by expressing their genetic variants. The chapter describes rodent models with manipulations for genetic susceptibility factors of mental illnesses in greater detail. A series of studies by Weinberger and associates has pioneered the possible correlation of brain dysfunction with genetic variations in susceptibility factors associated with mental illnesses. To identify mechanistic links from genetic factors to the phenotypes, especially those observed during brain development and maturation, a combination of human studies with animal experiments is expected.

Keywords

psychiatric disorderssubstance use disordersschizophreniagene identificationgenetic epidemiologyanxiety disordersmood disorders
Type
Chapter
Information
Principles of Psychiatric Genetics , pp. 69 - 78
Publisher: Cambridge University Press
Print publication year: 2012

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