Variation at the MJD locus in the major psychoses

Saleem, Quasar; Vijayakumar, M.; Mutsuddi, Mousumi; Chowdhary, Neerja; Jain, Sanjeev; Brahmachari, Samir K.

doi:10.1002/(sici)1096-8628(19980907)81:5<440::aid-ajmg14>3.0.co;2-c

Cited by 10 publications

(6 citation statements)

References 14 publications

(15 reference statements)

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“…The schizophrenia patients also had a larger mean number of triplet repeats at this locus, 22.27 versus 21.56. A study at the SCA3/MJD locus of 32 patients of Indian origin, comprising three schizophrenia patients and 29 with bipolar disorder, was carried out by Saleem et al [75]. No large expansions were observed in the studied patients, although two probands had 36 repeats, which is three repeats larger than the control population [75], but within the normal range for this locus ( Table 4).…”

Section: Comparison Studies Of Unstable Loci Associated With Known Nementioning

confidence: 94%

Anticipation and CAG•CTG repeat expansion in schizophrenia and bipolar affective disorder

Fortune

Kennedy²,

Vincent

2003

Curr Psychiatry Rep

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The genetic contribution to the etiologies of schizophrenia and bipolar affective disorder (BPAD) has been considered for many decades, with twin, family, and adoption studies indicating consistently that the familial clustering of affected individuals is accounted for mainly by genetic factors. Despite the strong evidence for a genetic component, very little is understood about the underlying genetic and molecular mechanisms for schizophrenia and BPAD. In the early 1990s, after the discovery of "dynamic mutation" or "unstable DNA" as a molecular basis for the genetic anticipation observed in Huntington's disease, myotonic dystrophy, and many others, and the recently rediscovered, albeit still controversial, evidence for genetic anticipation in major psychoses, the genetic epidemiology of schizophrenia and BPAD was re-evaluated to demonstrate strong endorsement for the unstable DNA model. Many of the non-Mendelian genetic features of schizophrenia and BPAD could be explained by the behaviour of unstable DNA, and several molecular genetic approaches became available for testing the unstable DNA hypothesis. However, despite promising findings in the mid-1990s, no trinucleotide repeat expansion has yet been identified as a cause of idiopathic schizophrenia or BPAD.

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Section: Comparison Studies Of Unstable Loci Associated With Known Nementioning

confidence: 94%

Anticipation and CAG•CTG repeat expansion in schizophrenia and bipolar affective disorder

Fortune

Kennedy²,

Vincent

2003

Curr Psychiatry Rep

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“…Bipolar and schizophrenia samples were obtained from the National Institute of Mental Health and Neurosciences, Bangalore. These patient samples have been used in earlier published studies (Saleem et al 1998;Saleem et al 2000) and informed consent was obtained from all individuals before extraction of blood.…”

Section: Methodsmentioning

confidence: 99%

“…In cases where the CAG repeats are part of the coding regions of the disease genes, they code for glutamine, and repeat expansion results in long polyglutamine tracts, which are thought to play a central role in the pathogenesis of these disorders (Ross et al 1999). Normal variations in glutamine repeats have also been implicated in psychiatric disorders, such as schizophrenia and bipolar disorder (Chandy et al 1998;Saleem et al 1998;Saleem et al 2000;Vincent et al 2000). While there have been few reports of expansions in the range seen in disorders caused by trinucleotide repeat expansions, most reports have indicated a trend towards larger repeats within the normal range in patients with psychiatric disorders (Vincent et al 2000).…”

Section: Introductionmentioning

confidence: 99%

The polyglutamine motif is highly conserved at the Clock locus in various organisms and is not polymorphic in humans

et al. 2001

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Circadian rhythms play a central role in diverse physiological phenomena and the recent years have witnessed the identification of a number of genes responsible for the maintenance of these rhythms. One of these is the Clock gene, which was first identified in mouse and subsequently in a large number of organisms, including humans. The human Clock gene has been proposed as a possible candidate for disorders affected by alterations of circadian rhythm, including bipolar disorder and schizophrenia. This gene contains a highly conserved polyglutamine motif, that in humans is coded for by CAG repeats. In view of the involvement of CAG repeat expansion in a number of neuro-psychiatric disorders, we have sought to determine the polymorphism status of CAG repeats at the Clock locus in humans. Our analysis of 190 unrelated individuals, who included patients suffering from bipolar disorder and schizophrenia, indicated that the repeat, which consisted of 6 CAG triplets, was not polymorphic in humans. An analysis of the repeat in non-human primates and other organisms revealed that the glutamine stretch is shortest in humans and baboons, and longest in Drosophila and zebrafish. A study of various Drosophila species revealed that the repeat number is highly polymorphic, ranging from 25 to 33 pure glutamine repeats. Unlike most other microsatellites, the CAG repeat stretch at the Clock locus in humans is smaller than its homologues in non-human primates. We propose that glutamine repeat size is functionally important in this gene and thus tightly regulated. The variation in repeat number is probably deleterious to the individual, resulting in the maintenance of a short and invariable repeat structure in the human population.

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“…Some of the patients and controls have been used in earlier published studies. 26,27 The number of patient and control samples used for the individual loci are given in Table 1.…”

Section: Selection Of Patients and Controlsmentioning

confidence: 99%

“…25 We have also earlier proposed that a difference in allele sizes or 'allele span' at such polymorphic trinucleotide repeat loci may also be implicated in bipolar disorder and schizophrenia. 26,27 As chromosome 22 has been repeatedly implicated in bipolar disorder and schizophrenia, we sought to test the hypothesis that susceptibility loci on this chromosome might contain expanded CAG repeats involved in the pathogenesis of these disorders. Taking advantage of the recent availability of the complete sequence of chromosome 22 28 we have mapped all CAG repeats Ն5 on this chromosome and studied the longest of these repeat tracts in regions previously Molecular Psychiatry implicated in bipolar disorder and schizophrenia and coding for genes expressed in the brain.…”

Section: Introductionmentioning

confidence: 99%

Association of CAG repeat loci on chromosome 22 with schizophrenia and bipolar disorder

et al. 2001

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Chromosome 22 has been implicated in schizophrenia and bipolar disorder in a number of linkage, association and cytogenetic studies. Recent evidence has also implicated CAG repeat tract expansion in these diseases. In order to explore the involvement of CAG repeats on chromosome 22 in these diseases, we have created an integrated map of all CAG repeats Ն5 on this chromosome together with microsatellite markers associated with these diseases using the recently completed nucleotide sequence of chromosome 22. Of the 52 CAG repeat loci identified in this manner, four of the longest repeat stretches in regions previously implicated by linkage analyses were chosen for further study. Three of the four repeat containing loci, were found in the coding region with the CAG repeats coding for glutamine and were expressed in the brain. All the loci studied showed varying degrees of polymorphism with one of the loci exhibiting two alleles of 7 and 8 CAG repeats. The 8-repeat allele at this locus was significantly overrepresented in both schizophrenia and bipolar patient groups when compared to ethnically matched controls, while alleles at the other three loci did not show any such difference. The repeat lies within a gene which shows homology to an androgen receptor related apoptosis protein in rat. We have also identified other candidate genes in the vicinity of this locus. Our results suggest that the repeats within this gene or other genes in the vicinity of this locus are likely to be implicated in bipolar disorder and schizophrenia. Molecular Psychiatry (2001) 6, 694-700.

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Variation at the MJD locus in the major psychoses

Cited by 10 publications

References 14 publications

Anticipation and CAG•CTG repeat expansion in schizophrenia and bipolar affective disorder

Anticipation and CAG•CTG repeat expansion in schizophrenia and bipolar affective disorder

The polyglutamine motif is highly conserved at the Clock locus in various organisms and is not polymorphic in humans

Association of CAG repeat loci on chromosome 22 with schizophrenia and bipolar disorder

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