Structural and copy number variants in the human genome: implications for psychiatry

Abstract

Copy number variants are small chromosomal deletions and duplications. When they alter the dose of genes critical for normal brain development and adult brain functioning they may cause severe disorders such as autism and schizophrenia. Numerous such loci have recently been identified. They are offering amazing leads for neuropsychiatric research.

The developmental trajectory of bipolar disorder

“…16 Essentially, evidence from this study and from other longitudinal studies suggest that neurodevelopmental disorders may be antecedents to psychotic spectrum illnesses, including atypical or psychotic spectrum bipolar disorder and that this may have a specific genetic basis. 28 Our third aim was to test the 'staging hypothesis' that we proposed based on our earlier observations and assessed initially using a simple sign test. 15,17 With longer observation and using more modelling techniques, we found evidence that high-risk offspring who go on to develop bipolar disorder do so in a predictable forward clinical sequence consistent with clinical staging.…”

Copy Number Variation Distribution in Six Monozygotic Twin Pairs Discordant for Schizophrenia

“…It has become apparent that CNVs are common in human populations and play a significant role in the etiology of complex diseases, including schizophrenia (Ahn et al, 2013; St Clair, 2013). However, it is not easy to identify disease-specific CNVs and establish their mode of action in the causation of the disease.…”

Cannabinoid Receptor Gene Variations in Drug Addiction and Neuropsychiatric Disorders

“…Such CNVs may have functional implications in gene dosage imbalances by loss or gain in the level of gene expression [48], and contribute to various complex human diseases. When CNVs alter the dose of genes critical for normal brain development and adult brain functioning, they may cause severe disorders such autism and schizophrenia [88]. But the vast majorities of most CNVs are harmless and impact human health when they alter gene expression or change gene dosage [88].…”

“…When CNVs alter the dose of genes critical for normal brain development and adult brain functioning, they may cause severe disorders such autism and schizophrenia [88]. But the vast majorities of most CNVs are harmless and impact human health when they alter gene expression or change gene dosage [88]. Significant advances have been made in mapping gene variations due to SNPs which were previously thought to be the most prevalent form of genetic variations.…”

“…Whether the larger CNR2 gene CNVs in Japanese alcoholics compared to nonalcoholics are associated with the disease is unknown and the phenotypic effects are often unclear and unpredictable, with larger CNVs [48,89]. However, the bigger the CNV, the more likely it will cause a change in gene dosage [88]. Therefore, the underlying pathogenic mechanism for the larger CNR2 gene CNV obtained in the sample analyzed in the alcoholics is currently unknown.…”