Detection of expanded CAG repeats in Bipolar Affective Disorder using the repeat expansion detection (RED) method

Lindblad, Kerstin; Nylander, Per-Olof; Bruyn, A. De; Sourey, Daniel; Zander, Cecilia; Engström, Christer; Holmgren, Gösta; Hudson, Tom; Chotai, Jayanti; Mendlewicz, Julien; Broeckhoven, Christine Van; Schalling, Martin; Adolfsson, Rolf

doi:10.1006/nbdi.1995.0006

Cited by 138 publications

(76 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This is in agreement with previous findings, where -30% of the normal population show expansions of i> 180 bp (Schalling et al 1993;Lindblad et al 1995). Two of these expansions were >240 bp, making possible a separate segregation analysis that indicated these longer alleles were unrelated to disease.…”

Section: Red Products In Healthy Spousessupporting

confidence: 93%

An expanded CAG repeat sequence in spinocerebellar ataxia type 7.

Lindblad¹,

Savontaus²,

Stevanin³

et al. 1996

Genome Res.

View full text Add to dashboard Cite

Expanded CAG repeat sequences have been identified in the coding region of genes mutated in several neurodegenerative disorders, including spinocerebellar ataxia type 1 and Machado-Joseph disease. In all disorders described to date the CAG expansion codes for an elongated polyglutamine chain. An increased polyglutamine chain size leads to a more severe disease, thus correlating with the genetic anticipation seen in repeat expansion disorders. Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant spinocerebellar ataxia with anticipation and a progressive degeneration of the cerebellar cortex. Using repeat expansion detection (RED), a method in which a thermostable ligase is used to detect repeat expansions directly from genomic DNA, we have analyzed 8 SCA7 families for the presence of CAG repeat expansions. RED products of 150-240 bp were found in all affected individuals and found to cosegregate with the disease (P < 0.000001, n = 66), indicating strongly that a CAG expansion is the cause of SCA7. On the basis of a previously established correlation between RED product sizes and actual repeat sizes in Machado-Joseph disease, we were able to estimate the average expansion size in SCA7 to be 64 CAG copies.

show abstract

Section: Red Products In Healthy Spousessupporting

confidence: 93%

An expanded CAG repeat sequence in spinocerebellar ataxia type 7.

Lindblad¹,

Savontaus²,

Stevanin³

et al. 1996

Genome Res.

View full text Add to dashboard Cite

show abstract

“…4 Finally, EO was reported to be involved in anticipation (increase in disease severity and decrease in age at onset in succeeding generations), as suggested in BPDs. [6][7][8][9] EO of MD could be an important variable in identifying some forms of MD that are more genetically homogeneous or may carry some degree of relatively increased genetic loading or phenotypic expression. 5 EO, as a specific phenotype, may be helpful to identify vulnerability genes (ie increase penetrance).…”

mentioning

confidence: 99%

Association between COMT (Val158Met) functional polymorphism and early onset in patients with major depressive disorder in a European multicenter genetic association study

et al. 2004

View full text Add to dashboard Cite

The available data from preclinical and pharmacological studies on the role of the C-O-methyl transferase (COMT) support the hypothesis that abnormal catecholamine transmission has been implicated in the pathogenesis of mood disorders (MD). We examined the relationship of a common functional polymorphism (Val108/158Met) in the COMT gene, which accounts for four-fold variation in enzyme activity, with 'early-onset' (EO) forms (less than or equal to 25 years) of MD, including patients with major depressive disorder (EO-MDD) and bipolar patients (EO-BPD), in a European multicenter case-control sample. Our sample includes 378 MDD (120 EO-MDD), 506 BPD (222 EO-BPD) and 628 controls. An association was found between the high-activity COMT Val allele, particularly the COMT Val/Val genotype and EO-MDD. These findings suggest that the COMT Val/Val genotype may be involved in EO-MDD or may be in linkage disequilibrium with a different causative polymorphism in the vicinity. The COMT gene may have complex and pleiotropic effects on susceptibility and symptomatology of neuropsychiatric disorders. Molecular Psychiatry (2005) 10, 598-605.

show abstract

“…8,9 Further, the repeat expansion detection (RED) method has identified subjects with larger RED products of (CAG) n in bipolar disorder or schizophrenia compared to controls, with the implication that a locus with an enlarged (CAG) repeat is etiologically associated with the illness. [10][11][12][13][14] However, not all studies have found this. 15,16 We recently described a highly polymorphic (observed heterozygozity 84%) and unstable CAG repeat locus (CTG18.1) in the third intron of the SEF2-1 gene.…”

mentioning

confidence: 99%

“…17 The most common allele is the (CAG) 11 , which with (CAG) [14][15][16][17] accounts for over 70% of alleles. The frequency of enlarged alleles (ϾCAG 40 ) is approximately 3% of the alleles, again comparable to previous studies.…”

mentioning

confidence: 99%

Allelic distribution of CTG18.1 in Caucasian populations: association studies in bipolar disorder, schizophrenia, and ataxia

et al. 2000

View full text Add to dashboard Cite

CTG18.1 is a highly polymorphic and unstable CTG repeat within an intron of the SEF2-1 gene. We tested the CTG18.1 repeat length in affective disorder, schizophrenia, and nonspecific ataxia; these diseases all have shown clinical evidence for anticipation. There was no difference in the allele frequencies comparing the controls and disease groups. The most common allele contains 11 CAGs (35%) followed by alleles with 14-17 CAGs (35%). There was no difference in the distribution of the alleles in the cases vs controls for ataxia (P = 0.11), affective disorders (P = 0.21), or schizophrenia (P = 0.26). The frequency of unstable CTG18.1 alleles was approximately 3% in a population of N. European descent and is not related to the phenotypes tested. Molecular Psychiatry (2000) 5, 439-442.

show abstract

Detection of expanded CAG repeats in Bipolar Affective Disorder using the repeat expansion detection (RED) method

Cited by 138 publications

References 0 publications

An expanded CAG repeat sequence in spinocerebellar ataxia type 7.

An expanded CAG repeat sequence in spinocerebellar ataxia type 7.

Association between COMT (Val158Met) functional polymorphism and early onset in patients with major depressive disorder in a European multicenter genetic association study

Allelic distribution of CTG18.1 in Caucasian populations: association studies in bipolar disorder, schizophrenia, and ataxia

Contact Info

Product

Resources

About