Association analysis of CAG repeats at theKCNN3 locus in Indian patients with bipolar disorder and schizophrenia

Saleem, Quasar; Sreevidya, V.S.; Sudhir, Jayanand; Savithri, J. Vijaya; Gowda, Y.; B-Rao, Chandrika; Benegal, Vivek; Majumder, Partha P.; Anand, Anuranjan; Brahmachari, Samir K.; Jain, Sanjeev

doi:10.1002/1096-8628(20001204)96:6<744::aid-ajmg9>3.0.co;2-z

Cited by 24 publications

(19 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The values which are indicated in parentheses are P-values which were obtained from chi-square analysis when comparison was between the present study and the other studies using MedCalc 7.6.0.0. Table 4: Clinical details of the patients with lower repeats than the normal range at SCA 8 locus At SCA8 locus repeats varied from 18-33 with 90% of the alleles having less than 27 repeats in northern Indian population [22] and in the present study repeats varied from 16-37 (Figure 2) with 44% of the alleles having >27 repeats which indicates that greater repeat size at SCA 8 locus is more in southern population of India. The frequencies of large normal alleles at SCA 8 locus were quite high when compared with other populations (Table 3).…”

Section: Discussionsupporting

confidence: 49%

Molecular Analysis of CTG/CTA Repeats at SCA8 Locus in South Indian Population

Lone¹,

Poornima²

2014

J Neurol Disord

View full text Add to dashboard Cite

Spinocerebellar ataxias are a group of phenotypically and genetically heterogenous disorders characterized by progressive degeneration of the cerebellum with overlapping symptoms. A novel form of SCA has been described with triplet repeat expansions in the 3 UTR of the SCA8 gene and is caused by expansion of a CTG/CTA repeat in the ataxin-8 opposite strand gene (ATXN8OS) located on chromosome 13q21. Analysis of CTA/CTG repeats in SCA8 gene was performed in 188 ataxia patients and 100 healthy volunteers without any neurological signs or family history. The repeat length was found to be highly polymorphic. We were unable to find any individual with pathogenic repeat length in SCA8 gene, when we used the already established pathogenic repeat criteria. However, repeats >35 (4.7%) were exclusively found in patients only and none of the controls suggesting that these repeat sizes could be pathogenic for our population. The frequency of LN alleles was also found to be higher than reported for other populations. The percentage of LN alleles at SCA 8 locus was 65% and 47% in patients and controls. In the present study three patients also exhibited repeats lower than the normal range and the pathological implications of these needs to be explored.

show abstract

Section: Discussionsupporting

confidence: 49%

Molecular Analysis of CTG/CTA Repeats at SCA8 Locus in South Indian Population

Lone¹,

Poornima²

2014

J Neurol Disord

View full text Add to dashboard Cite

show abstract

“…Calcium channels have been previously implicated in bipolar disorder and schizophrenia. 27 The gene which encodes synaptogyrin 1, a protein which is involved in presynaptic vesicle formation in neurons, 36 is also found within 2 Mb of the 22CH3 locus. While this manuscript was under review, Mirnics et al reported altered levels of synaptoMolecular Psychiatry gyrin 1 in the prefrontal cortex of some of the patients suffering from schizophrenia using microarray analysis.…”

Section: Discussionmentioning

confidence: 99%

“…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%

See 1 more Smart Citation

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

et al. 2001

View full text Add to dashboard Cite

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.

show abstract

“…Twin studies have also been used in biometric studies to determine the most likely disease model. Cardno and colleagues performed such an analysis on pooled twin data and found that a model containing additive genetic and environmental effects gave the best fit, with a heritability of 83% (95% CI [74][75][76][77][78][79][80][81][82][83][84][85][86][87][88][89][90] and specific environmental effects of 17% (95% CI 10-26) [13]. Discordant MZ twin studies have also shown that the children of both affected and unaffected MZ twins have similar risks of schizophrenia-like psychosis [14].…”

Section: Evidence For a Genetic Basismentioning

confidence: 99%

Recent advances in the genetics of schizophrenia

Waterworth¹,

Bassett

Brzustowicz³

2002

CMLS, Cell. Mol. Life Sci.

View full text Add to dashboard Cite

The genetic etiology of schizophrenia, a common and debilitating psychiatric disorder, is supported by a wealth of data. Review of the current findings suggests that considerable progress has been made in recent years, with a number of chromosomal regions consistently implicated by linkage analysis. Three groups have shown linkage to 1q21-22 using similar models, with HLOD scores of 6.5, 3.2, and 2.4. Other replicated loci include 13q32 that has been implicated by two independent groups with significant HLOD scores (4.42) or NPL values (4.18), and 5p14.1-13.1, 5q21-33, 8p21-22, and 10p11-15, each of which have been reported as suggestive by at least three separate groups. Different studies have also replicated evidence for a modest number of candidate genes that were not ascertained through linkage. Of these, the greatest support exists for the DRD3 (3q13.3), HTR2A (13q14.2), and CHRNA7 (15q13-q14) genes. The refinement of phenotypes, the use of endophenotypes, reduction of heterogeneity, and extensive genetic mapping have all contributed to this progress. The rapid expansion of information from the human genome project will likely further accelerate this progress and assist in the discovery of susceptibility genes for schizophrenia. A greater understanding of disease mechanisms and the application of pharmacogenetics should also lead to improvements in therapeutic interventions.

show abstract

Association analysis of CAG repeats at theKCNN3 locus in Indian patients with bipolar disorder and schizophrenia

Cited by 24 publications

References 23 publications

Molecular Analysis of CTG/CTA Repeats at SCA8 Locus in South Indian Population

Molecular Analysis of CTG/CTA Repeats at SCA8 Locus in South Indian Population

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

Recent advances in the genetics of schizophrenia

Contact Info

Product

Resources

About