CTG18.1 and ERDA-1 CAG/CTG Repeat Size in Bipolar Disorder

doi:10.1006/nbdi.1999.0249

Neurobiology of Disease

Volume 6, Issue 4, August 1999, Pages 302-307

https://doi.org/10.1006/nbdi.1999.0249 Get rights and content

Abstract

Several groups have reported association between large CAG/CTG repeat sequences in the genome and bipolar disorder using the Repeat Expansion Detection (RED) method. Unfortunately, the RED method cannot identify the specific repeat(s) responsible for these findings but it has recently been proposed that around 90% of the large CAG/CTG repeats detected by RED can be explained by repeat size at either CTG18.1, which maps to 18q21.1, or ERDA-1 (also known as Dir 1), which maps to 17q21.3. These data suggest that the previous associations between bipolar disorder and large CAG/CTG repeats might be explained at least in part by a specific association between bipolar disorder and either or both of these loci. However, using a case control study design, we find no evidence for such associations. Thus we conclude that in our sample, the previous RED associations are not a result of large CAG/CTG repeats at CTG18.1 or ERDA-1.

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Cited by (16)

Molecular genetics of affective disorders
2004, Progress in Neuro-Psychopharmacology and Biological Psychiatry
Evidence for familial aggregation in Affective Disorders (AD) has been provided in classical studies. Linkage and association genetic studies have been proposed to detect genetic factors implicated in AD. However, findings from molecular genetic studies remain inconclusive. Nevertheless, current research is focusing on the phenotypes, both sub- and endophenotypes. In addition, recent advances in technology, such as microarrays, provide new tools in psychiatric genetics. These different approaches offer a new optimism era in the search of genetic factors in AD.
Trinucleotide repeat expansions: Do they contribute to bipolar disorder?
2001, Brain Research Bulletin
Citation Excerpt :
However, a causal link between the very large ERDA1 allele and this case of major psychosis has still to be proven and will need screening in large numbers of cases, controls, and families. Overall, large alleles at ERDA1 were estimated to explain between 28% [30] and 74% [114] of RED products larger than 120 bp. Breschel et al. [7] reported the isolation and characterisation of CTG18.1, a CAG/CTG repeat on chromosome 18q21.1 that is frequently expanded in healthy individuals.
It has long been known that bipolar disorder has a true but complex genetic background. Reports on genetic anticipation in bipolar disorder opened the way to a new approach for genetic studies. Indeed, anticipation, a decreasing age at onset, and/or increasing disease severity in successive generations, were recently explained by an expansion of trinucleotide repeats in monogenic diseases like Huntington’s disease and Fragile X syndrome. The involvement of trinucleotide repeat expansions in bipolar disorder received even more support when studies reported association of large CAG/CTG repeats with bipolar disorder. Even though a large number of studies have been conducted, this association is still unexplained. Here, we review the studies investigating the trinucleotide repeat expansion hypothesis in bipolar disorder. Studies on anticipation, on association of anonymous large CAG/CTG repeats and on specific trinucleotide repeats are critically analysed and discussed, showing a field with precipitate conclusions or inconclusive results. The analysis suggests that there are indications, though disputable, supporting the trinucleotide repeat expansion hypothesis in bipolar disorder, but no conclusive evidence has been hithereto provided.
Molecular genetics of bipolar disorder
2001, Neuroscience Research
Alteration of monoaminergic neurotransmission is implicated in the pathophysiology of bipolar disorder (manic-depressive illness). Candidate genes participating in monoaminergic neurotransmission, especially serotonin transporter and monoamine oxidase A, may be associated with bipolar disorder. And the regulating regions of these genes and the molecules participating in intracellular signal transduction are now under investigation. To date, 13 whole genome positional cloning studies have been performed and many candidate loci identified. Using patients from a pedigree in which schizophrenia, depression or bipolar disorder have been linked with a balanced translocation at 1 and 11, candidate pathogenetic genes were cloned as DISC1 (disrupted in schizophrenia-1) and DISC2. Recently, pathogenetic mutations have been identified in two genetic diseases frequently co-morbid with mood disorder; WFS1 for Wolfram syndrome and ATP2A2 (SERCA2) for Darier's disease. Transmission of bipolar disorder may be characterized by anticipation and parent-of-origin effect, and extended CTG repeat at SEF2-1B gene was identified from a bipolar patient. However, its pathogenetic role was not supported by subsequent studies. Association of bipolar disorder with mitochondrial DNA has also been suggested. The role of genomic imprinting is also possible because linkage to 18p11 is limited to paternally transmitted pedigrees. These results warrant further study of molecular genetics of bipolar disorder.
Genetics of affective disorders
2001, European Neuropsychopharmacology
Despite substantial evidence for heritability in affective disorders the contributing genes have proven elusive. Here we discuss the genetic epidemiology of depression, as well as methodological issues and results from molecular genetic studies. There has been rapid advances in genetics, genomics and statistical modelling, facilitating the search for molecular mechanisms underlying affective disorders and several strategies reviewed in this paper hold promise to provide progress in the field. Considering the poorly understood biological basis of vulnerability to affective disorders, the identification of genes involved in the pathophysiology will unravel mechanisms and pathways that could permit more personalized therapeutic strategies and result in new targets for pharmacological intervention.
The genetic basis of bipolar disorder
2011, Bipolar Disorder: Causes, Diagnosis and Treatment
The genetic basis of Bipolar Disorder
2011, Psychiatry Research Journal

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Neurobiology of Disease

Abstract

References (27)

Variation of the CGG repeat at the Fragile-X site results in genetic instability: Resolution of the Sherman paradox

Cell

A novel and unstable CAG/CTG trinucleotide repeat on chromosome 17q: A candidate for hereditary neurodegenerative disorders

Genomics

Detection of expanded repeats in bipolar affective disorder using the repeat expansion detection (RED) method

Neurobiol. Dis.

A splice variant of E2-2 basic helix-loop-helix protein represses the brain-specific fibroblast growth factor 1 promoter through the binding to an imperfect E-box

J. Biol. Chem.

Expanded trinucleotide CAG repeats in families with bipolar affective disorder

Biol. Psychiatr.

Anticipation and imprinting in Japanese familial mood disorders

Psychiatr. Res.

Expansion of 50 CAG/CTG repeats excluded in schizophrenia by application of a highly efficient approach using RED and a PCR screening set

Am. J. Hum. Genet.

A novel, heritable, expanding CTG repeat in an intron of the SEF2-1 gene on chromosome 18q21.1

Hum. Mol. Genet.

Genetic anticipation and imprinting in bipolar I illness

Br. J. Psychiatr.

Exclusion of expansion of 50 CAG/CTG trinucleotide repeats in bipolar disorder

Am. J. Psychiatr.

Cell

Analysis of CAG repeat size in chinese subjects with schizophrenia and bipolar affective disorder using the repeat expansion detection method

Biol. Psychiatr.

Two commonly expanded CAG/CTG repeat loci involvement in affective disorders

Mol. Psychiatr.

Cited by (16)

Molecular genetics of affective disorders

Trinucleotide repeat expansions: Do they contribute to bipolar disorder?

Molecular genetics of bipolar disorder

Genetics of affective disorders

The genetic basis of bipolar disorder

The genetic basis of Bipolar Disorder

Regular ArticleCTG18.1 and ERDA-1 CAG/CTG Repeat Size in Bipolar Disorder

Abstract

Cell

Genomics

Neurobiol. Dis.

J. Biol. Chem.

Biol. Psychiatr.

Psychiatr. Res.

Expansion of 50 CAG/CTG repeats excluded in schizophrenia by application of a highly efficient approach using RED and a PCR screening set

Am. J. Hum. Genet.

A novel, heritable, expanding CTG repeat in an intron of the SEF2-1 gene on chromosome 18q21.1

Hum. Mol. Genet.

Genetic anticipation and imprinting in bipolar I illness

Br. J. Psychiatr.

Exclusion of expansion of 50 CAG/CTG trinucleotide repeats in bipolar disorder

Am. J. Psychiatr.

Cell

Analysis of CAG repeat size in chinese subjects with schizophrenia and bipolar affective disorder using the repeat expansion detection method

Biol. Psychiatr.

Two commonly expanded CAG/CTG repeat loci involvement in affective disorders

Mol. Psychiatr.

Regular Article
CTG18.1 and ERDA-1 CAG/CTG Repeat Size in Bipolar Disorder