Chromosomal localization of long trinucleotide repeats in the human genome by fluorescence in situ hybridization

Haaf, Thomas; Sirugo, Giorgio; Kídd, Kenneth K.; Ward, David C.

doi:10.1038/ng0296-183

Cited by 33 publications

(19 citation statements)

References 8 publications

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“…[3][4][5] Initial studies in major psychosis investigating trinucleotide repeats have shown encouraging results. [6][7][8][9][10][11] Other data, however, would suggest that the occurrence of unstable DNA in both SCZ and BPAD may be less prevalent or of a more subtle nature than previously thought. [12][13][14][15][16] Attempts to identify specific CAG/CTG repeat loci responsible for the observed shift towards larger repeats in affecteds observed in several studies have so far been unsuccessful.…”

Section: Introductionmentioning

confidence: 99%

“…analysis RED was performed as described by Schalling et al, 3 with modifications, 12 using approximately 5 g of genomic DNA and 100 ng of the phosphorylated oligonucleotide (CTG) 10 . DNAs from two myotonic dystrophy individuals with large CAG repeats were used as positive controls.…”

Section: Repeat Expansion Detection (Red)mentioning

confidence: 99%

“…12 Genotyping at SEF2-1B and ERDA1 SCZ and BPAD individuals and matched controls were genotyped for SEF2-1B and ERDA1 using PCR as described by Breschel et al 23 and Nakamoto et al, 24 and the PCR product then underwent electrophoresis on 6% denaturing polyacrylamide gels. DNA was transferred by blotting to Hybond-N + (Amersham Canada, Oakville, ON, Canada) membranes, and hybridized with a 3Ј-end labelled (CAG) 10 probe. The Sequamark (Research Genetics, Huntsville, AL, USA) sequencing ladder was used to size alleles.…”

Section: Repeat Expansion Detection (Red)mentioning

confidence: 99%

“…[12][13][14][15][16] Attempts to identify specific CAG/CTG repeat loci responsible for the observed shift towards larger repeats in affecteds observed in several studies have so far been unsuccessful. [17][18][19][20][21] A large, unstable repeat identified in a Danish SCZ pedigree 22 and localized to chromosome 18 10 has recently been cloned, sequenced and characterised. 23 This CTG repeat occurs in an intron of the gene encoding the transcription factor SEF2-1B.…”

Section: Introductionmentioning

confidence: 99%

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Analysis of genome-wide CAG/CTG repeats, and at SEF2-1B and ERDA1 in schizophrenia and bipolar affective disorder

et al. 1999

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A shift towards larger CAG/CTG triplet repeats and schizophrenia (SCZ) and bipolar affective disorder (BPAD) has been detected by several recent studies, using the Repeat Expansion Detection (RED) technique, however no specific loci have been shown to be responsible for this shift. Further analyses by our group of RED (CTG) 10 ligation products amongst an extended sample of patients and comparison with controls matched for age, sex and ethnicity show no significant differences in distribution (P = 0.23, n = 95; P = 0.93, n = 91, for SCZ and BPAD respectively). Alleles at two recently discovered unstable trinucleotide repeat loci at 18q21.1 (SEF2-1B) and 17q21.3 (ERDA1) have also been analysed in affecteds and matched controls. We observed no increase in frequency of larger alleles (Ͼ Ͼ Ͼ37 repeats) in affected individuals at SEF2-1B (BPAD: P = 0.95, n = 100; SCZ: P = 0.61, n = 97) or at ERDA1 (BPAD: P = 0.4, n = 101; SCZ: P = 0.05, n = 151, with larger alleles more frequent in controls). Our findings suggest that larger CAG/CTG repeats at these loci are neither major contributory factors to the etiology of psychosis, nor in linkage disequilibrium with a gene that is. Furthermore, when the RED results were compared to allele sizes at SEF2-1B and ERDA1, it was observed that a majority of SCZ, BPAD and control individuals with large RED products had a large allele at either or both sites (78% for RED products у у у270 bp; 62% for RED products у у у180 bp).

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Section: Introductionmentioning

confidence: 99%

Section: Repeat Expansion Detection (Red)mentioning

confidence: 99%

Section: Repeat Expansion Detection (Red)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Analysis of genome-wide CAG/CTG repeats, and at SEF2-1B and ERDA1 in schizophrenia and bipolar affective disorder

et al. 1999

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“…Another expanded chromosome 18 allele recently cloned by Breschel,15 was first identified using fluorescence in situ hybridisation (FISH) on metaphases obtained from a schizophrenic individual. 16 This repeat was subsequently excluded from expansion in CEPH pedigree 1334, suggesting the presence of at least two non-allelic CAG repeats which can show expansions on chromosome 18.…”

Section: Introductionmentioning

confidence: 99%

An integrated map of chromosome 18 CAG trinucleotide repeat loci

et al. 1999

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Expansions of trinucleotide CAG repeats have been demonstrated in at least eight neurodegenerative disorders, and suggested to occur in several others, including bipolar disorder and schizophrenia. Chromosome 18 loci have been implicated in bipolar disorder pedigrees by linkage analysis. To address this putative link between chromosome 18 CAG trinucleotide repeats and neuropsychiatric illness, we have screened a chromosome 18 cosmid library (LL18NCO2 ² AD ² ) and identified 14 novel candidate loci. Characterisation of these loci involved repeat flank sequencing, estimation of polymorphism frequency and mapping using FISH as well as radiation hybrid panels. These mapped trinucleotide loci will be useful in the investigation of chromosome 18 in neurodegenerative or psychiatric conditions, and will serve to integrate physical and radiation hybrid maps of chromosome 18.

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Trinucleotide Repeat Expansion and Neuropsychiatric Disease

Margolis¹,

McInnis²,

Rosenblatt³

et al. 1999

Arch Gen Psychiatry

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Trinucleotide, or triplet, repeats consist of 3 nucleotides consecutively repeated (e.g., CCG CCG CCG CCG CCG) within a region of DNA, a not uncommon motif in the genome of humans and other species. In 1991, a new type of genetic mutation was discovered, known as a dynamic or expansion mutation, in which the number of triplets in a repeat increases and the length becomes unstable. During the past decade, nearly 20 diseases-including Huntington disease, 2 forms of the fragile X syndrome, and myotonic dystrophy-caused by trinucleotide repeat expansions have been identified. The unstable nature of the expanded repeat leads to remarkable patterns of inheritance in these diseases, distinctly at odds with traditional notions of mendelian genetics. We review the clinical and genetic features of these disorders, with a particular emphasis on their psychiatric manifestations. We also critically examine the hypothesis that expansion mutations may have an etiologic role in psychiatric diseases such as bipolar disorder, schizophrenia, and autism.

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Chromosomal localization of long trinucleotide repeats in the human genome by fluorescence in situ hybridization

Cited by 33 publications

References 8 publications

Analysis of genome-wide CAG/CTG repeats, and at SEF2-1B and ERDA1 in schizophrenia and bipolar affective disorder

Analysis of genome-wide CAG/CTG repeats, and at SEF2-1B and ERDA1 in schizophrenia and bipolar affective disorder

An integrated map of chromosome 18 CAG trinucleotide repeat loci

Trinucleotide Repeat Expansion and Neuropsychiatric Disease

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