cDNAs with long CAG trinucleotide repeats from human brain

Margolis, Russell L.; Abraham, Meena R.; Gatchell, Shawn B.; Li, Shengbo Eben; Kidwai, Arif S.; Breschel, Theresa S.; Stine, O. Colin; Callahan, Colleen; McInnis, Melvin G.; Ross, Christopher A.

doi:10.1007/s004390050476

Cited by 100 publications

(75 citation statements)

References 74 publications

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“…The mRNA for this repeat-containing region was also identified in a study designed to pick up CAG repeatcontaining genes expressing in the brain. 31 The loci, 22CH2 and 22CH3 containing nine and eight repeats, respectively, were chosen over 22CH5 (eight CAG repeats) and 22CH6 (nine CAG repeats) because both of the former were in the vicinity of previously implicated markers. Furthermore, both 22CH2 and 22CH3 were found in the coding regions and were expressed in the brain, with the repeats coding for glutamine.…”

Section: Resultsmentioning

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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Section: Resultsmentioning

confidence: 99%

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

et al. 2001

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“…These include known and previously mapped genes (MYBL2, TNRC9/CAGF9, h-l(3)mbt) (Noben-Trauth et al, 1996;Margolis et al, 1997;Koga et al, 1999), a mapped UniGene (CGI-53) (Lai et al, 2000), an unknown mapped EST (sts-T63166), and an exontrapped transcript not previously mapped (SGK). The h-l(3)mbt gene encodes a member of the polycomb group family of proteins and is the human homologue of a tumor suppressor gene in Drosophila (Koga et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Identification of candidate genes on chromosome band 20q12 by physical mapping of translocation breakpoints found in myeloid leukemia cell lines

et al. 2001

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Deletions of the long arm of chromosome 20 have been reported in a wide range of myeloid disorders and may re¯ect loss of critical tumor suppressor gene(s). To identify such candidate genes, 65 human myeloid cell line DNAs were screened by polymerase chain reaction (PCR) for evidence of allelic loss at 39 highly polymorphic loci on the long arm of chromosome 20. A mono-allelic pattern was present in eight cell lines at multiple adjacent loci spanning the common deleted regions (CDRs) previously de®ned in primary hematological samples, suggesting loss of heterozygosity (LOH) at 20q. Fluorescence in situ hybridization (FISH) was then performed using a series of yeast arti®cial chromosomes (YACs) ordered in the CDR, and in ®ve of eight cell lines, the deletions resulted from cytogenetically detectable whole chromosomal loss or large interstitial deletion, whereas in another cell line deletion was associated with an unbalanced translocation. LOH in the CMK megakaryocytic cell line, which has a hypotetraploid karyotype, was associated with a der(20)t(1;20)(q32;q12)x2 leading to complete deletion of the CDR. Three additional unbalanced translocations were found within the CDR and all three breakpoints mapped to a single YAC. We then used a series of P1 arti®cial chromosomes (PACs) spanning this YAC clone, and two PACs produced`split' signals suggesting that they each span one of these breakpoints. Exon trapping using PACs that overlap the breakpoint regions yielded portions of six genes and evaluation of these genes as candidate tumor suppressor genes is underway. The limited information available about these genes suggests that the h-l(3)mbt gene is the most attractive candidate. Oncogene (2001) 20, 4150 ± 4160.

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“…Polymorphic and/or long CAG repeats (n = 20) consisting of more than 10 consecutive units and previously found in human cDNA libraries [15][16][17] were also tested including 2.116, 2.119, i.181, i.182, 15 12501r, b01500t, and g02502r, 16 and CTG1a, CTG3a, CTG4a, CTG7a, CTG20a, CAGF9, F28, H1, H16, H26, H32, H38, H39, H44, H45, L69, L85, L114, L234, and L237, some of them predicted to code for a polygln stretch. 17 Finally, seven CAG/CTG repeats (GCT1C9, GCT4B10, GCT5E11, GCT16E06, GCT10D04, GCT10C10, and GCT10H06) isolated from genomic DNA and consisting of more than 15 consecutive units were tested as well. 18 The selection and use of primers suitable for detection of CAG expansion in DNAs from COS family NFI was performed as previously described.…”

Section: Screening Of Candidate Genes For Cag Expansionmentioning

confidence: 80%

“…Twenty-seven CAG repeats found in cDNAs [15][16][17] and CAG/CTG repeats isolated from genomic DNA 18 consisting of more than 10-15 consecutive units were also tested for expansion in NFI (see Methods). All the candidates tested showed unenlarged CAG repeat alleles, and no difference in the size Figure 1 Detection of PGE in COS. Electrophoresis was performed on 50 g (4-20% polyacrylamide gradient gels) or 60 g (long 10% polyacrylamide gels) of protein from LCL extracts (see Table 1).…”

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confidence: 99%

Detection of polyglutamine expansion in a new acidic protein: a candidate for childhood onset schizophrenia?

et al. 1999

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Polyglutamine expansion (PGE) encoded by a CAG repeat underlies eight inherited neurodegenerative diseases, among which is Huntington's disease. CAG expansion has also been reported in schizophrenia, suggesting a role for PGE. To investigate the potential role of PGE as a candidate for schizophrenia, we searched for PGE in nuclear families comprising a patient affected by childhood onset schizophrenia (COS, a rare and severe form of the disease) as a variation of the candidate gene approach for identifying susceptibility genes. We tested lymphoblastoid cell lines from COS patients (n = 32) by Western blot analysis with 1C2, a monoclonal antibody that specifically recognizes long polyglutamines. Eight of 11 unrelated black American COS patients showed a 60-kDa (approximately) band indicative of PGE. A strong 60-kDa band (suggestive of a large PGE) was detected in two of the eight positive patients. A weaker 60-kDa band (suggestive of a smaller and non pathogenic PGE) was detected in some unaffected parents or sibs of these two COS patients, and in six other black American COS patients. The strong and weak PGE signals were found to correspond to two different proteins. Unrelated black Americans unaffected by COS (n = 38) were negative for the strong 60-kDa PGE signal. Healthy white Americans (n = 53) were negative for both the strong and weak 60-kDa PGE signals. Two-dimensional gel analysis suggested that the strong PGE signal corresponds to an acidic (pI 4 approximately) protein and resulted in a more precise estimation (52-57 kDa) of its relative mass. This protein appeared to be not represented in Genbank, as suggested by the exclusion of several candidate CAG repeats. Our data suggest that this acidic protein might be a candidate for COS.

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cDNAs with long CAG trinucleotide repeats from human brain

Cited by 100 publications

References 74 publications

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

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

Identification of candidate genes on chromosome band 20q12 by physical mapping of translocation breakpoints found in myeloid leukemia cell lines

Detection of polyglutamine expansion in a new acidic protein: a candidate for childhood onset schizophrenia?

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