Publications
132 results found
Bauer P, Laccone F, Rolfs A, et al., 2004, Trinucleotide repeat expansion in SCA17/TBP in white patients with Huntington's disease-like phenotype., J Med Genet, Vol: 41, Pages: 230-232
Morris-Rosendahl DJ, Lehmann-Horn F, Grissmer S, et al., 2004, A splice variant of hSK3, hSK3_ex1c abolishes hSK3 currents when coexpressed with the hSK3 isoform in tsA cells, 48th Annual Meeting of the Biophysical Society, Publisher: BIOPHYSICAL SOCIETY, Pages: 129A-129A, ISSN: 0006-3495
Wittekindt OH, Dreker T, Morris-Rosendahl DJ, et al., 2004, A novel non-neuronal hSK3 isoform with a dominant-negative effect on hSK3 currents., Cell Physiol Biochem, Vol: 14, Pages: 23-30, ISSN: 1015-8987
We have identified a hSK3-transcript, hSK3_ex1c, which is generated by alternative splicing. Isoform hSK3_ex1c lacks the cytosolic N-terminus and the first transmembrane helix and is exclusively expressed in non-neuronal tissues. hSK3 transfected tsA cells showed a Ca2+-activated K+ current in patch-clamp experiments, whereas hSK3_ex1c transfected cells and cells co-transfected with both isoforms did not. We fused both isoforms to fluorescence proteins and observed hSK3 localization predominantly in the plasma membrane. The co-expression of hSK3 + hSK3_ex1c resulted in their cytoplasmic co-localization. Thus, hSK3_ex1c has a dominant-negative effect on hSK3 by preventing its transport into the plasma membrane.
Wittekindt OH, Visan V, Tomita H, et al., 2003, A scyllatoxin-insensitive isoform of the human SK3 channel, Annual Meeting of the American-Society-of-Human-Genetics, Publisher: UNIV CHICAGO PRESS, Pages: 514-514, ISSN: 0002-9297
Wittekindt OH, Visan VM, Morris-Rosendahl DJ, et al., 2003, A seyllatoxin insensitive isoform of the human SK3-channel, 47th Annual Meeting of the Biophysical-Society, Publisher: BIOPHYSICAL SOCIETY, Pages: 92A-92A, ISSN: 0006-3495
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- Citations: 1
Aigner L, Uyanik G, Couillard-Despres S, et al., 2003, Somatic mosaicism and variable penetrance in doublecortin-associated migration disorders., Neurology, Vol: 60, Pages: 329-332
X-linked isolated lissencephaly sequence (XLIS) and subcortical band heterotopia (SBH) are allelic disorders caused by mutations in the doublecortin (DCX) gene. This genetic analysis of seven families revealed four novel mutations in the DCX gene. The authors detected a high rate of somatic mosaicism in male and female patients with variable penetrance of bilateral SBH including nonpenetrance in a heterozygous woman. In addition, the authors implemented prenatal diagnosis in a family with SBH/XLIS.
Staner L, Uyanik G, Correa H, et al., 2002, A dimensional impulsive-aggressive phenotype is associated with the A218C polymorphism of the tryptophan hydroxylase gene: a pilot study in well-characterized impulsive inpatients., Am J Med Genet, Vol: 114, Pages: 553-557, ISSN: 0148-7299
Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the biosynthesis of serotonin, and association and linkage studies of its variants in suicidal and impulsive-aggressive behavior have brought conflicting results. This pilot study was designed to investigate whether TPH A218C genotypes could be associated with impulsive behavioral tendencies (IBTs) in consecutively admitted nonpsychotic nonorganic inpatients. Patients (20 females and 34 males; age, 38.8 +/- 11.8) did not differ from healthy nonimpulsive controls (16 females and 11 males; age, 35.2 +/- 10.2) regarding TPH genotypes, but in the patients, the number of IBT was related to the presence of the 218C allele. It was concluded that impulsive-aggressive behavior may be associated with the TPH genotype in well-characterized impulsive patients and that the present results stress the importance of considering impulsiveness-aggressiveness in studies investigating the relationship between suicidal behavior and TPH genotypes.
Bauer I, Gencik M, Laccone F, et al., 2002, Trinucleotide repeat expansions in the junctophilin-3 gene are not found in Caucasian patients with a Huntington's disease-like phenotype., Ann Neurol, Vol: 51, ISSN: 0364-5134
Morris-Rosendahl DJ, Back E, 2002, The human genome: chromosome 22q11 deletion syndrome., Am J Psychiatry, Vol: 159, ISSN: 0002-953X
Morris-Rosendahl DJ, Back E, 2002, The human genome: detecting chromosomal deletions: Angelman and Prader-Willi syndromes., Am J Psychiatry, Vol: 159, ISSN: 0002-953X
Tamminga CA, Morris-Rosendahl DJ, Back E, 2002, The human genome, American Journal of Psychiatry, Vol: 159, ISSN: 0002-953X
Bowen T, Williams N, Norton N, et al., 2001, Mutation screening of the KCNN3 gene reveals a rare frameshift mutation., Mol Psychiatry, Vol: 6, Pages: 259-260, ISSN: 1359-4184
Robinson TJ, Wittekindt O, Pasantes JJ, et al., 2000, Stable methylation patterns in interspecific antelope hybrids and the characterization and localization of a satellite fraction in the Alcelaphini and Hippotragini., Chromosome Res, Vol: 8, Pages: 635-643, ISSN: 0967-3849
Conflicting data has recently appeared concerning altered methylation patterns in interspecific mammalian hybrids and the potential this may hold for driving karyotypic evolution. We report no detectable methylation difference in the genomic DNA of different interspecific F1 antelope hybrids (family Bovidae) and their parent species using the methylation-sensitive enzyme HpaII and its methylation insensitive isoschizomer MspI. However, both enzymes released a tandemly repeated satellite array. Characterization of the repeat using Southern blotting and a combination of sequencing, fluorescence in-situ hybridization (FISH) and C-banding, shows some similarity in the family of repeats between the hybridizing antelope species groups, and that the satellite is localized in the centromeric C-band positive regions of the chromosomes. Moreover, although there is little meaningful sequence homology with the well characterized bovine 1.715 satellite DNA, there is 86% sequence similarity with the sheep/goat satellite I, suggesting that they are related and are likely to have originated and evolved separately from the bovine unit.
Laccone F, Engel U, Holinski-Feder E, et al., 1999, DNA analysis of Huntington's disease: five years of experience in Germany, Austria, and Switzerland., Neurology, Vol: 53, Pages: 801-806, ISSN: 0028-3878
OBJECTIVE: To review the direct DNA testing for Huntington's disease (HD) in Germany, Switzerland, and Austria from 1993 to 1997, and to analyze the population with regard to age structure, gender, and family history. METHODS: Twelve laboratories (nine in Germany, two in Austria, and one in Switzerland) recorded data pertaining to repeat number, gender, age at molecular diagnosis, and family history of probands. The molecular test was categorized as either diagnostic (for symptomatic individuals), presymptomatic (for individuals at risk), and prenatal (for pregnancies at risk). RESULTS: A total of 3,090 HD patients, 992 individuals at risk, and 24 fetuses were investigated using DNA analysis. The clinical diagnosis was confirmed in 65.6% of patients. A total of 38.5% of individuals at risk inherited an expanded CAG repeat. The female-to-male ratio showed a distinct predominance of women both in the diagnostic and presymptomatic groups. Of the fetuses tested, six were carriers of an expanded CAG repeat. Two pregnancies were interrupted; one pregnancy was not. No information about the parents' decision was obtained for the remaining three pregnancies. CONCLUSIONS: Approximately 20% of the estimated 10,000 HD patients living in Germany, Switzerland, and Austria have been identified by DNA analysis (total population, approximately 100 million; incidence of HD, 1:10,000). Assuming a ratio of HD patients to individuals at risk of 1:3, approximately 30,000 individuals are, in principle, eligible for a presymptomatic test. Less than 3 to 4% of individuals at risk have requested a presymptomatic test. This shows that the assumed enormous request of predictive testing has not occurred. More surprisingly, prenatal diagnoses were found to be rare.
Meissner B, Purmann S, Schürmann M, et al., 1999, hSKCa3:: a candidate gene for schizophrenia?, PSYCHIATRIC GENETICS, Vol: 9, Pages: 91-96, ISSN: 0955-8829
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- Citations: 14
Wittekindt O, Schwab SG, Burgert E, et al., 1999, Association between hSKCa3 and schizophrenia not confirmed by transmission disequilibrium test in 193 offspring/parents trios., Mol Psychiatry, Vol: 4, Pages: 267-270, ISSN: 1359-4184
A possible association between the small conductance calcium-regulated potassium channel gene, hSKCa3, and schizophrenia has recently been described by Chandy et al using a case-control design with patients with schizophrenia (n=141) and matched controls (n = 158). The gene may be considered as an excellent candidate gene for psychiatric disorders, since it plays a role in modulating neuronal firing patterns by regulating the slow component of after hyperpolarisation. In addition, the gene contains a highly polymorphic trinucleotide sequence (CAG) within exon 1, which encodes a polyglutamine stretch. The possible contribution of unstable trinucleotide repeats to the development of psychiatric disorders has previously been discussed. Chandy et al reported an over-representation of alleles with higher repeat number in schizophrenics as compared to controls (P = 0.0035). In an attempt to replicate these findings, we have performed a family-based study with 193 offspring/parent combinations using a sample of 49 multiplex families (two or more affected siblings with parents) and a second sample of 83 simplex families (one affected offspring with parents). No evidence for the association of longer repeats with schizophrenia was obtained when each sample was tested separately or when both samples were combined and tested for transmission disequilibrium.
Wittekindt O, Jauch A, Burgert E, et al., 1998, The human small conductance calcium-regulated potassium channel gene (hSKCa3) contains two CAG repeats in exon 1, is on chromosome 1q21.3, and shows a possible association with schizophrenia, NEUROGENETICS, Vol: 1, Pages: 259-265, ISSN: 1364-6745
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- Citations: 36
Hoehe MR, Wendel B, Grunewald I, et al., 1998, Brief research communication: Serotonin transporter (5-HTT) gene polymorphisms are not associated with susceptibility to mood disorders, American Journal of Medical Genetics - Neuropsychiatric Genetics, Vol: 81, Pages: 1-3, ISSN: 1552-4841
In a population-based association study, we tested the hypothesis that allelic variants of the human serotonin transporter (5-HTT) gene confer susceptibility to mood disorders. Both a biallelic repeat polymorphism in the 5' promotor region that differentially modulates gene expression and a second intron variable-number-tandem-repeat (VNTR) marker were genotyped in 294 controls and 115 patients with mood disorders. Subjects were of West European descent and included 36 patients with major depressive disorder (MDD) and 79 patients with bipolar I disorder (BD). No significant differences in genotype or allele frequencies were found at either locus between controls and combined patients, nor between controls and MDD or BD patients separately. Thus, our data do not support the association between depressive disorder and a nine-repeat allelic variant of the 5-HTT VNTR marker recently reported by Ogilvie et al. (Lancet 347:731-733, 1996). More importantly, no association between alleles conveying functional differences in 5-HTT gene expression and MIlD or BD could be found. Taken together, our data suggest that the 5-HTT gene is not commonly involved in the susceptibility to mood disorders.
Hoehe MR, Wendel B, Grunewald I, et al., 1998, Serotonin transporter (5-HTT) gene polymorphisms are not associated with susceptibility to mood disorders., Am J Med Genet, Vol: 81, Pages: 1-3, ISSN: 0148-7299
In a population-based association study, we tested the hypothesis that allelic variants of the human serotonin transporter (5-HTT) gene confer susceptibility to mood disorders. Both a biallelic repeat polymorphism in the 5' promotor region that differentially modulates gene expression and a second intron variable-number-tandem-repeat (VNTR) marker were genotyped in 294 controls and 115 patients with mood disorders. Subjects were of West European descent and included 36 patients with major depressive disorder (MDD) and 79 patients with bipolar I disorder (BD). No significant differences in genotype or allele frequencies were found at either locus between controls and combined patients, nor between controls and MDD or BD patients separately. Thus, our data do not support the association between depressive disorder and a nine-repeat allelic variant of the 5-HTT VNTR marker recently reported by Ogilvie et al. (Lancet 347:731-733, 1996). More importantly, no association between alleles conveying functional differences in 5-HTT gene expression and MDD or BD could be found. Taken together, our data suggest that the 5-HTT gene is not commonly involved in the susceptibility to mood disorders.
Chandy KG, Fantino E, Wittekindt O, et al., 1998, CAG repeats in a K+ channel gene, <i>hKCA3</i>:: A candidate for schizophrenia and bipolar disorder?, Publisher: BIOPHYSICAL SOCIETY, Pages: A26-A26, ISSN: 0006-3495
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- Citations: 1
Burgert E, Crocq MA, Bausch E, et al., 1998, No association between the tyrosine hydroxylase microsatellite marker HUMTH01 and schizophrenia or bipolar I disorder, PSYCHIATRIC GENETICS, Vol: 8, Pages: 45-48, ISSN: 0955-8829
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- Citations: 16
Chandy KG, Fantino E, Wittekindt O, et al., 1998, Isolation of a novel potassium channel gene hSKCa3 containing a polymorphic CAG repeat: a candidate for schizophrenia and bipolar disorder?, Mol Psychiatry, Vol: 3, Pages: 32-37, ISSN: 1359-4184
Many human hereditary neurodegenerative diseases are caused by expanded CAG repeats, and anonymous CAG expansions have also been described in schizophrenia and bipolar disorder. We have isolated and sequenced a novel human cDNA encoding a neuronal, small conductance calcium-activated potassium channel (hSKCa3) that contains two arrays of CAG trinucleotide repeats. The second CAG repeat in hSKCa3 is highly polymorphic in control individuals, with alleles ranging in size from 12 to 28 repeats. The overall allele frequency distribution is significantly different in patients with schizophrenia compared to ethnically matched controls (Wilcoxon Rank Sum test, P=0.024), with CAG repeats longer than the modal value being over-represented in patients (Fisher Exact test, P=0.0035). A similar, non-significant, trend is seen for patients with bipolar disorder. These results provide evidence for a possible association between longer alleles in the hSKCa3 gene and both of these neuropsychiatric diseases, and emphasize the need for more extensive studies of this new gene. Small conductance calcium-activated K+ channels play a critical role in determining the firing pattern of neurons. These polyglutamine repeats may modulate hSKCa3 channel function and neuronal excitability, and thereby increase disease risk when combined with other genetic and environmental effects.
Morris-Rosendahl DJ, Burgert E, Uyanik G, et al., 1997, Analysis of the CAG repeats in the SCA1 and B37 genes in schizophrenic and bipolar I disorder patients: tentative association between B37 and schizophrenia., Am J Med Genet, Vol: 74, Pages: 324-330, ISSN: 0148-7299
We have genotyped unrelated French Alsatian schizophrenic and bipolar I disorder (BPD) patients and matched controls for the polymorphic CAG repeats within the genes for spinocerebellar ataxia type 1 (SCA1) and dentatorubral-pallidoluysian atrophy (B37), in order to test their possible involvement in these disorders. No alleles with abnormally expanded repeats were found in either gene in patients and controls. Differences in allele and genotype frequencies for the SCA1 CAG repeat between patients and controls were not significant, thus providing no support for its role as a possible positional candidate gene for schizophrenia and BPD in our patients. Chi square testing revealed a significant result (P = 0.019) for an association between the B37 CAG repeat on chromosome 12p and schizophrenia. This result was more significant when only schizophrenics with a positive family history were compared with controls (P = 0.0001). The frequencies of alleles with 14, 12, and 15 CAG repeats differed the most, respectively, between schizophrenics and controls. When choosing the median of the B37 allele distribution (15 CAG repeats) as a threshold, there were significantly more controls than schizophrenics in the group with longer alleles (15 or more repeats) and more schizophrenics with shorter alleles (P = 0.002 by Fisher exact test). No particular genotype was associated with schizophrenia. This result possibly indicates linkage disequilibrium with another locus on chromosome 12p and therefore deserves further attention. No association was found between the B37 CAG repeat and patients with BPD.
Delbrück SJW, Wendel B, Grunewald I, et al., 1997, A novel allelic variant of the human serotonin transporter gene regulatory polymorphism, CYTOGENETICS AND CELL GENETICS, Vol: 79, Pages: 214-220, ISSN: 0301-0171
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- Citations: 55
Morris-Rosendahl DJ, Schriever-Schwemmer G, Robinson TJ, 1996, Derivation and characterization of a somatic cell hybrid containing the portion of mouse chromosome 11 (MMU11) homologous to human chromosome 17q., J Hered, Vol: 87, Pages: 252-258, ISSN: 0022-1503
To contribute to the physical gene map of mouse chromosome 11 (MMU11) and to extend the mapping resources available for this chromosome, we have produced mouse x rat somatic cell hybrids containing only bands B5 to E of MMU11. Characterization of the hybrids by polymerase chain reaction (PCR) amplification and Southern blot analyses of MMU11 markers revealed two hybrids, T16Ad14B and T16Ad19A, that had selectively retained the 3(11) translocation product containing distal MMU11 (bands B5-E). Cytogenetic analysis of the hybrid T16Ad14B by fluorescence in situ hybridization (FISH) and conventional G-banding confirmed the presence of the 3(11) translocation chromosome. Mapping of markers in both the T16Ad14B and T16Ad19A hybrids localized the T16Ad translocation breakpoint between the proximal markers Atplb2 and Acrb and the more distal markers Scya2 and Mpo. Loci for D11Mit5, Rpo2-1, Trp53, Glut4, Acrb, and Atplb2 could all be localized proximal to the T16Ad breakpoint in band B5, between bands B1 and B5 on MMU11.
FRISCHAUF AM, OBERMAYR F, CHADWICK B, et al., 1995, COSMID CONTIGS AND TRANSCRIPTS IN THE REGION OF THE GORLIN SYNDROME GENE, AMERICAN JOURNAL OF HUMAN GENETICS, Vol: 57, Pages: 339-339, ISSN: 0002-9297
Rothschild CB, Freedman BI, Hodge R, et al., 1995, Fructose-1,6-bisphosphatase: genetic and physical mapping to human chromosome 9q22.3 and evaluation in non-insulin-dependent diabetes mellitus., Genomics, Vol: 29, Pages: 187-194, ISSN: 0888-7543
PCR primers specific to the human liver fructose-1,6-bisphosphatase (FBP) gene were designed and used to isolate a cosmid clone. Physical mapping of the FBP cosmid by FISH, and genetic mapping of an associated GA repeat polymorphism (PIC = 0.35), located the liver FBP gene to chromosome 9q22.3 with no recombination between FBP and the index markers D9S196 (Zmax = 13.2), D9S280 (Zmax = 11.7), D9S287 (Zmax = 15.6), and D9S176 (Zmax = 14.4). Amplification using FBP exon-specific primers with a YAC contig from this region of chromosome 9 further refined the placement of FBP genomic sequences to an approximately 1.7-cM region flanked by D9S280 and D9S287, near the gene for Fanconi anemia group C. Precise localization of the FBP gene enabled evaluation of FBP as a candidate gene for maturity-onset diabetes of the young (MODY) and non-insulin-dependent diabetes (NIDDM) in both Caucasian and African-American families, using the highly informative markers D9S287 and D9S176. Although FBP is a rate-limiting enzyme in gluconeogenesis, using both parametric and nonparametric analysis there was no evidence for linkage of FBP to diabetes in these families.
Shankman S, Spurdle AB, Morris D, et al., 1995, Presence of Y chromosome sequences and their effect on the phenotype of six patients with Y chromosome anomalies., Am J Med Genet, Vol: 55, Pages: 269-275, ISSN: 0148-7299
The extent of Y chromosome material was determined in 6 southern African subjects with sex chromosome anomalies. Four of the subjects were phenotypically female, and 2 were phenotypically male. Molecular and cytogenetic findings were correlated with phenotypic expression. An X;Y translocation was found in both male subjects, and in one female subject. The remaining female subjects were characterized by an isodicentric Y, an isochromosome Yq, and a micromarker of undetermined origin, respectively. The individuals were tested for the presence of a number of Y-specific DNA sequences. Molecular findings were generally compatible with the cytogenetic findings, and also with the phenotypic sex of the patients. All the female subjects had Y material and all but one were negative for the sex determining region of the Y (SRY). The somatic Ullrich-Turner-like findings present in 3 of the females were attributed to either the presence of a 45,X cell line and/or a single copy of Xp. The males both showed X;Y translocations without any detectable loss of Y DNA. Although molecularly very similar, the disparate clinical findings in these 2 subjects could have been accounted for by different X inactivation patterns.
Farndon PA, Morris DJ, Hardy C, et al., 1994, Analysis of 133 meioses places the genes for nevoid basal cell carcinoma (Gorlin) syndrome and Fanconi anemia group C in a 2.6-cM interval and contributes to the fine map of 9q22.3., Genomics, Vol: 23, Pages: 486-489, ISSN: 0888-7543
Four disease genes (NBCCS, ESS1, XPAC, FACC) map to 9q22.3-q31. A fine map of this region was produced by linkage and haplotype analysis using 12 DNA markers. The gene for nevoid basal cell carcinoma syndrome (NBCCS, Gorlin) has an important role in congenital malformations and carcinogenesis. Phase-known recombinants in a study of 133 meioses place NBCCS between (D9S12/D9S151) and D9S176. Haplotype analysis in a two-generation family suggests that NBCCS lies in a smaller interval of 2.6 cM centromeric to D9S287. These flanking markers will be useful clinically for gene tracking. Recombinants also map FACC (Fanconi anemia, group C) to the same region, between (D9S196/D9S197) and D9S287. The recombination rate between (D9S12/D9S151) and D9S53 in males is 8.3% and 13.2% in females, giving a sex-specific male:female ratio of 1:1.6 and a sex-averaged map distance of 10.4 cM. No double recombinants were detected, in agreement with the apparently complete level of interference predicted from the male chiasmata map.
Morris DJ, Reis A, 1994, A YAC contig spanning the nevoid basal cell carcinoma syndrome, Fanconi anaemia group C, and xeroderma pigmentosum group A loci on chromosome 9q., Genomics, Vol: 23, Pages: 23-29, ISSN: 0888-7543
Nevoid basal cell carcinoma syndrome (NBCCS, Gorlin syndrome) is an autosomal dominant disorder, characterized primarily by multiple basal cell carcinomas, epithelium-lined jaw cysts, and palmar and plantar pits, as well as various other features. Loss of heterozygosity studies and linkage analysis have mapped the NBCCS gene to chromosome 9q and suggested that it is a tumor suppressor. The apparent sensitivity of NBCCS patients to UV and X-irradiation raises the possibility of hypersensitivity to DNA-damaging reagents or defective DNA repair being etiological in the disorder. The recent mapping of the Fanconi anaemia group C (FACC) and xeroderma pigmentosum complementing group A (XPAC) genes to the same region on 9q has led us to begin the molecular dissection of the 9q22-q31 region. PCR analysis of the presence or absence of 10 microsatellite markers and exons 3 and 4 of the XPAC and FACC genes, respectively, allowed us to order 12 YACs into an overlapping contig and to order the markers as follows: D9S151/D9S12P1-D9S12P2-D9S197-D9S196-D9 S280-FACC-D9S287/XPAC-D9S180-D9S6-D9 S176 . Sizing of the YACs has provided an initial estimate of the size of the NBCCS candidate region between D9S12 and D9S180 to be less than 1.65 Mb.
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