Saturday, January 16, 2016

The Genomics of Mental Illness

Mental illness covers a wide range of diseases including schizophrenia (SCZ), autism spectrum disorder (ASD), chronic depression and bipolar disorder (BPD).  The aberrant behavior associated with these disorders has long been ascribed to factors other than that of a genetic or organic origin.  On account of the tremendous strides that have been made in the fields of molecular biology and human genetics, there is a new understanding of the role of human genes in the development of psychiatric diseases.

Daniel H. Geschwind and Jonathan Flint from the Department of Neurology, Psychiatry and Human Genetics at the David Geffen School of Medicine in University of California in Los Angeles have published a review article in the Journal Science (Vol 349, No 625, pp 1489-1493) in which they describe the current scientific understanding of the role genes play in mental illness.  Within the body of this review, they make a number of salient points.

Due to remarkable technological advances, variations at millions of Single Nucleotide Polymorphisms (SNPs) within the human genome can be detected.  Furthermore, with the use of microarrays, genome-wide association studies (GWASs) can be performed that can establish associations between disease states and common genetic alleles.  As a result of such exhaustive studies, it appears that GWASs generally lie within regulatory regions of the genome.  Since regulatory sites usually lie within close proximity to the genes that are regulated, it is not unreasonable to assume that it is such functional genes that are affected.
In addition, microarrays have also identified copy number variants (CNVs) associated with both SCZ and ASD.  These CNVs are the result of either a gain or loss of DNA involving DNA segments > 1 kilobase (kb) in size.   Another area of intense investigation involves genomic sequencing that focuses on the complete protein coding sequence also referred to as whole-exome sequencing (WES).  WES reveals the DNA sequences that have the coding information within the entire genome for all the proteins destined for production.  To date, tens of thousands of individuals have been analyzed in this way.  From this extensive data, rare protein variants have been shown to be associated with SCZ and ASD.

Although the application of these methodologies have contributed greatly to the understanding of the role of genes in mental illness, the various mental illness disease states appear to involve a multiplicity of genetic loci making it difficult to pinpoint the precise etiology of the disease process.  However, great progress continues to be made in this area of research, making it more likely that complete molecular mechanisms will eventually be uncovered.