A Novel Long and Unstable CAG/CTG Trinucleotide Repeat on Chromosome 17q

Ikeuchi, Takeshi; Sanpei, Kazuhiro; Takano, Hiroki; Sasaki, Hidenao; Tashiro, Kunio; Cancel, Géraldine; Brice, Alexis; Bird, Thomas D.; Schellenberg, G D; Pericak‐Vance, Margaret A.; Welsh‐Bohmer, Kathleen A.; Clark, Lorraine N.; Wilhelmsen, Kirk C.; Tsuji, Shoji

doi:10.1006/geno.1998.5266

Cited by 42 publications

(37 citation statements)

References 20 publications

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“…Given the high frequencies of large alleles at SEF2-1B and ERDA1 in our affected and control populations as well as others, [23][24][25]27 such high frequencies are likely the case in other studies which have reported significant increases in CAG/CTG repeat distribution amongst affected individuals. [6][7][8][9]11,29 A recently published study has reported weak evidence of association of large repeats at SEF2-1B (but not ERDA1) with BPAD.…”

Section: Discussionsupporting

confidence: 64%

“…No significant increases of larger repeat alleles were found for SEF2-1B or ERDA1 in either SCZ or BPAD in our sample populations. We have previously identified an intergenerational expansion at ERDA1 from a mildly affected father to a daughter severely affected with childhood onset depression, 26 with larger alleles (115 repeats) than any previously reported 24,25,27 or observed in our population samples. The evidence presented in this study, however, suggests that neither SEF2-1B nor ERDA1, at least for repeats within the size range observed in our affected and control populations, are pathogenic in major psychosis, and thus it is necessary to search for and study other potentially diseaseassociated repeats.…”

Section: Discussioncontrasting

confidence: 39%

“…Neither size-range of large alleles appears to co-segregate with major psychosis. 22,23 A second large repeat, ERDA1, 24,25 localizes to 17q21.3 and appears to have a high frequency of large alleles in the normal population. This repeat appears to demonstrate instability, and evidence of expansion above the range seen in the normal popu-lation has been reported in a family with childhood onset depression.…”

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: Discussionsupporting

confidence: 64%

Section: Discussioncontrasting

confidence: 39%

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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“…The RED assay has previously been used for detection of pathogenic TREs in several dis-orders, including myotonic dystrophy, 15 MachadoJoseph disease 17 and spinocerebellar ataxia type 7. 16 Two recently identified loci, ERDA1 (also known as Dir-I) on chromosome 17q21.3 18,19 and CTG18.1 (also known as 7.6A) on chromosome 18q21.1, 20 display expanded alleles in normal individuals. CTG18.1 is a particularly interesting locus as it is present within a gene that is expressed in multiple organs including the brain.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 1998

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An association between bipolar affective disorder and CAG/CTG trinucleotide repeat expansions (TRE) has previously been detected using the repeat expansion detection (RED) method. Here we report that 89% of RED products (CAG/CTG repeats) Ͼ120 nt (n = 202) detected in affective disorder patients as well as unaffected family members and controls correlate with expansions at two repeat loci, ERDA1 on chromosome 17q21.3 and CTG18.1 on 18q21.1. In a set of patients and controls in which we had previously found a significant difference in RED size distribution, the frequency of expansions at the CTG18.1 locus was 13% in bipolar patients (n = 60) and 5% in controls (n = 114) (P Ͻ 0.07) with a significantly different size distribution (P Ͻ 0.03). A second set of patients were ascertained from 14 affective disorder families showing anticipation. Twelve of the families had members with RED products Ͼ120 nt. The RED product distribution was significantly different (P Ͻ 0.0007) between affected (n = 53) and unaffected (n = 123) offspring. Using PCR, a higher frequency (P Ͻ 0.04) of CTG18.1 expansions as well as a different (P Ͻ 0.02) repeat size distribution was seen between affected and unaffected offspring. In addition, a negative correlation between RED product size and the age-of-onset could be seen in affected offspring (r s = −0.3, P = 0.05, n = 43). This effect was due to an earlier onset in individuals with long CTG18.1 expansions. No difference in ERDA1 expansion frequency was seen either between bipolar patients (35%, n = 60) and matched controls (29%, n = 114), or between affected and unaffected offspring in the families. We conclude that expanded alleles at the CTG18.1 locus confers an odds ratio of 2.6-2.8 and may thus act as a vulnerability factor for affective disorder, while the ERDA1 locus seems unrelated to disease.

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“…It is therefore possible that the disease in the large SCA8 kindred 2 might be caused by another mutation in, or closely linked to, the same gene. Indeed, large alleles of other polymorphic trinucleotide loci were found in controls of specific origins [3][4][5][6][7][8][9] .…”

mentioning

confidence: 99%