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.
