bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of GABAA receptors and alcohol dependence and the effects of genetic imprinting
Authors: Song Jiuzhou , Koller Daniel L. , Foroud Tatiana , Carr Kristie , Zhao Jinghua , Rice John , Nurnberger John I. , Begleiter Henri , Porjesz Bernice , Smith Tom L. , Schuckit Marc A. , Edenberg Howard J. 
Published: January 2003

AbstractGABA receptor genes have been postulated as candidates affecting the risk for alcoholism. The potential association between genes encoding five subunits of the GABAA receptors and alcoholism (alcohol dependence) was analyzed in the multiplex alcoholic pedigrees collected by the Collaborative Study on the Genetics of Alcoholism (COGA) using family‐based association tests. We found consistent, although weak, linkage disequilibrium between GABRB1 (located on chromosome 4) and alcoholism (P < 0.03). Genes encoding GABRA1 and GABRA6, on chromosome 5, did not provide evidence for association with alcoholism. GABRA5 and GABRB3, on chromosome 15, were reported to be expressed uniparentally from the paternal chromosome. Analyses of paternal transmission of alleles of GABRA5 provided evidence for association with alcoholism, particularly in the Caucasian population and with the stricter ICD‐10 definition of alcoholism (P < 0.004). Evidence of association was also observed during paternal transmission with GABRB3 in the Caucasian population (P < 0.007). Maternal transmissions provided no evidence for association. These data are consistent with an association between the expressed alleles in the GABAA‐gene cluster on chromosome 15 and alcoholism that is modulated by genetic imprinting. © 2003 Wiley‐Liss, Inc.
Genetic refinement and physical mapping of a 2.3 Mb probable disease region associated with a bipolar affective disorder susceptibility locus on chromosome 4q35
Authors: Badenhop Renee F. , Moses Melissa J. , Scimone Anna , Adams Linda J. , Kwok John B.J. , Jones Anne‐Marie , Davison Gail , Evans Mary R. , Kirkby Kenneth C. , Hewitt Jane E. , Donald Jennifer A. , Mitchell Philip B. , Schofield Peter R. 
Published: January 2003

AbstractA susceptibility locus for bipolar affective disorder has been mapped to chromosome 4q35 in a large multigenerational pedigree. We have expanded this analysis to include 55 pedigrees (674 individuals, 214 affecteds). The evidence for linkage to 4q35 was strengthened in this larger cohort, with a maximum two‐point LOD score of 3.2 for marker D4S1652. Several other markers in the region gave LOD scores greater than 1.5. Non‐parametric analysis provided additional support for linkage to the 4q35 region. To further refine this region, haplotype analysis was carried out in 16 of the 55 pedigrees that showed evidence of linkage. As there is no evidence for an ancestral haplotype, nor a one‐to‐one correspondence between the disease and putative disease haplotype, we undertook an analysis based on pedigree‐specific, identical‐by‐descent allele‐sharing in order to define a probable disease region. This analysis indicated that the percentage sharing of alleles, identical‐by‐descent, in affecteds of all linked pedigrees increases from 60% at the centromeric markers to 75% for markers at the telomere. Maximal allele sharing occurred between markers D4S3051 and 4qTEL13 with this 24 cM region defining a probable disease region. We have constructed a physical map of the 4q35 interval consisting of a YAC contig and BAC clones. Based on this map the probable disease region between D4S3051 and 4qTEL13 corresponds to only 2.3 Mb. This region is very gene poor with only three known genes indicated from the YAC/BAC map. The small number of genes will facilitate systematic screening for variations associated with bipolar disorder. © 2003 Wiley‐Liss, Inc.
Heritability of attention problems in children: I. cross‐sectional results from a study of twins, age 3–12 years
Authors: Rietveld M.J.H. , Hudziak J.J. , Bartels M. , van Beijsterveldt C.E.M. , Boomsma D.I. 
Published: January 2003

AbstractMultiple twin studies of attention problems (AP) from the Child Behavior Checklist or ADHD from the DSM criteria have reported on the genetic and environmental influences on these behaviors. The majority of these have studied AP and ADHD symptoms in twin samples combined across wide age spans, combined rater information and both genders. Thus, it is possible that the results are complicated by developmental, informant, and gender differences. The purpose of this study was to assess for the genetic and environmental contributions to overactive behavior (a syndrome highly related to AP in 7‐, 10‐, and 12‐years olds) in 3‐years olds (3,671 twin pairs), and attention problems in 7‐ (3,373 twin pairs), 10‐ (2,485 twin pairs), and 12‐years olds (1,305 twin pairs) while controlling for developmental, gender and rater contrast contributions. Using a cross‐sectional twin design, contributions from genetic additive, genetic dominance, unique environmental and rater contrast effects were estimated for CBCL maternal reports. We found that genetic influences on overactive behavior and attention problems are high across an age span that covers pre‐school and elementary school age. Although girls display less problem behavior compared to boys, heritability estimates were found equal for both genders at each age. Environmental experiences that are unique to the individual accounted for the remaining influence. At the age of 3 years, a rater contrast effect was detected. We hypothesize that the contrast effect represents a maternal rater bias effect that is dependent on the age of the twins. The implications of these findings are discussed with reference to the clinical setting and in the context of future research. © 2003 Wiley‐Liss, Inc.
Relationship between functional dopamine D2 and D3 receptors gene polymorphisms and neuroleptic malignant syndrome
Authors: Mihara Kazuo , Kondo Tsuyoshi , Suzuki Akihito , Yasui‐Furukori Norio , Ono Shingo , Sano Akira , Koshiro Kazuko , Otani Koichi , Kaneko Sunao 
Published: January 2003

AbstractOur previous study has suggested that the TaqI A polymorphism of dopamine D2 receptor gene (DRD2) is associated with the predisposition to neuroleptic malignant syndrome (NMS). However, the specificity of this polymorphism as a predictor of NMS dose not seem to be sufficient enough. Meanwhile, it has been shown that the non‐carriers of Del allele of the −141C Ins/Del polymorphism in the promoter region of DRD2 have lower dopamine D2 receptor in the brain than the carriers. In addition, dopamine D3 receptor gene has a Ser9Gly polymorphism, which may alter the receptor function. The present study examined the association between these three polymorphisms and the development of NMS to investigate if a combination of these polymorphisms could increase the specificity as markers for NMS. The subjects were 17 psychiatric patients who had developed NMS (13 patients with schizophrenia, 3 with major depression, and 1 with dementia of the Alzheimer's type) and 163 schizophrenic patients who had never developed this syndrome. The frequency of the A1 allele was significantly (P = 0.012) higher in the patients who had developed NMS (59%) than in the patients who had not (35%). The proportion of the A1 carriers was significantly (P = 0.003) higher in the patients with NMS (16/17: 94%) than in those without the syndrome (93/163: 57%). However, no significant differences were found in the allele and genotype frequencies of the other two polymorphisms between the two groups. The present study suggests that only the TaqI A polymorphism is at least partly useful as a predictor of NMS, but the −141 C Ins/Del and Ser9Gly polymorphisms are not. © 2003 Wiley‐Liss, Inc.
Association of the 3′ UTR transcription factor LBP‐1c/CP2/LSF polymorphism with late‐onset Alzheimer's disease
Authors: Luedecking‐Zimmer Erin , DeKosky Steven T. , Nebes Robert , Kamboh M. Ilyas 
Published: January 2003

AbstractAlzheimer's disease (AD) is a genetically heterogeneous neurodegenerative disorder. To date, apolipoprotein E (apoE) is the only established susceptibility gene for late‐onset AD. ApoE accounts for less than 50% of the risk of AD, indicating the presence of other unknown susceptibility loci. Linkage studies have indicated chromosome 12 as the most likely location for another late‐onset AD locus. We examined seven polymorphisms in five candidate genes located in and around the linkage peaks on chromosome 12 in 564 cases and 523 controls. The genes included complement component 1R (C1R), vitamin D receptor (VDR), scavenger‐receptor B1 (SR‐B1), low‐density lipoprotein receptor related protein 1 (LRP1), and transcription factor LBP‐1c/CP2/LSF. We found no association with C1R, VDR, SR‐B1, and LRP1 polymorphisms. However, the frequency of the A allele of the 3′ (untranslated region) UTR LBP‐1c/CP2/LSF polymorphism was higher in controls than cases (0.071 vs. 0.051; P = 0.042) with an adjusted odds ratio (OR) of 0.65 (95% confidence interval [CI]: 0.43–0.96; P = 0.0498). Our data suggest that the LBP‐1c/CP2/LSF polymorphism may have a moderate protective effect against the risk of AD. © 2003 Wiley‐Liss, Inc.
Testing the test—why pursue a better test for Huntington disease?
Authors: Timman Reinier , Maat‐Kievit Anneke , Brouwer‐DudokdeWit Christine , Zoeteweij Moniek , Breuning Martijn H. , Tibben Aad 
Published: January 2003

AbstractIn 1993, the gene mutation for Huntington disease (HD) was identified and testing became possible with a reliability of >99%, without the need for co‐operation of relatives. In 1997, a systematic information program offered the mutation retest to individuals who had earlier received a linkage test result for HD, which has a residual uncertainty of 1–9%. The characteristics of 129 individuals tested by linkage analysis for HD are reported on, as well as the reasons for their reassessment by mutation testing. Three groups were compared: (1) people who were retested between 1993 and 1997, before this study had started, (2) people who were retested after we provided information, and (3) persons who refrained from retesting. Nearly half of the linkage‐tested individuals were retested, with the exception of noncarriers with a residual risk of 1 or 2%. Of them, less than one out of five were retested. Carriers with a hopeful view on the future (BHS) and a better sense of well‐being (GHQ) were more likely to have the retest. Female carriers were also more likely to have the retest before we contacted them. Noncarriers who were retested were more anxious (HADS) than noncarriers who refrained from the retest. Retestees were younger at the time of testing. No risk reversals were revealed by this study. © 2003 Wiley‐Liss, Inc.
Tridimensional personality questionnaire trait of harm avoidance (anxiety proneness) is linked to a locus on chromosome 8p21
Authors: Zohar Ada H. , Dina Christian , Rosolio Naama , Osher Yamima , Gritsenko Inga , Bachner‐Melman Rachel , Benjamin Jonathan , Belmaker Robert H. , Ebstein Richard P. 
Published: January 2003

AbstractHuman personality traits are moderately heritable but only recently have specific polymorphisms been associated with particular personality dimensions especially anxiety‐related and novelty‐seeking traits. The first genome‐wide scan for personality traits was recently carried out by Cloninger et al. [1998: Am J Med Genet 81:313–317] and his colleagues and they reported that a region on 8p21 showed linkage to TPQ Harm Avoidance, an anxiety‐related personality trait. Towards replicating and extending these results, we examined both 8p21 and two additional chromosomal regions (1q21–24 and 22q12–13) for linkage to TPQ personality traits by genotyping at least three microsatellite markers in each region in a group of 384 sibling pairs. We found evidence for linkage to TPQ HA at 8p21–23 (Lod score = 2.907) confirming in an independent sample the initial findings by Cloninger and his colleagues. © 2003 Wiley‐Liss, Inc.
Possible parent‐of‐origin effect of Dopa decarboxylase in susceptibility to bipolar affective disorder
Authors: Børglum A.D. , Kirov G. , Craddock N. , Mors O. , Muir W. , Murray V. , McKee I. , Collier D.A. , Ewald H. , Owen M.J. , Blackwood D. , Kruse T.A. 
Published: January 2003

AbstractDopa decarboxylase (DDC) catalyses the synthesis of both dopamine and serotonin as well as trace amines suggested to possess neuromodulating capabilities. We have previously reported evidence suggesting an association between DDC and bipolar affective disorder (BPAD) [Børglum et al., 1999]. To further investigate the possible role of DDC in BPAD, we analyzed a 1‐ and a 4‐bp deletion variant—both of putative functional significance—in two new samples: a case‐control sample with 140 cases and 204 controls, and 100 case‐parents trios. We also tested for association in subjects with familial disease in both the new and the previously investigated samples. The previously reported association was not replicated in either of the new samples. However, a preponderance of the 1‐bp deletion was increased by analysis of the familial cases separately for all case‐control samples investigated, indicating a possible association with familial disease (combined analysis, P = 0.02). In the trio sample, a preferential paternal transmission of the 4‐bp deletion was observed (P = 0.006). DDC is located next to the imprinted gene GRB10, which is expressed specifically from the paternal allele in fetal brains. Increased transmission of paternal DDC alleles has also been suggested in attention deficit hyperactivity disorder. We suggest that DDC might confer susceptibility to BPAD predominantly when paternally transmitted. © 2003 Wiley‐Liss, Inc.
Association of EEG coherence and an exonic GABABR1 gene polymorphism
Authors: Winterer Georg , Smolka Michael , Samochowiec Jerzy , Ziller Mario , Mahlberg Richard , Gallinat Jürgen , Rommelspacher Hans‐Peter , Herrmann Werner M. , Sander Thomas 
Published: January 2003

AbstractThe GABAB receptor 1 gene is mapped to chromosome 6p21.3 within the HLA class I region close to the HLA‐F gene. Susceptibility loci for epilepsy and schizophrenia have been mapped in this region. Based on pharmacological evidence, it has been suggested that GABAB receptors may play a crucial role in the synchronization of EEG oscillations, which in turn can be abnormal in neuropsychiatric disorders. In the present study, the hypothesis was tested, whether three exonic variants of the gene encoding the human GABAB receptor (GABABR1) modify cortical synchronization measured as scalp‐recorded EEG‐coherence. Two principal components of EEG coherence (frontal coherence, parietotemporal coherence) were investigated in 104 healthy subjects during three conditions: resting EEG, activated EEG, and event‐related EEG. No significant associations were found between the frontal coherence component and any polymorphism or between the parietotemporal coherence component and the exon 1a1 polymorphism. However, parietotemporal coherence showed statistically highly significant associations across all three experimental conditions with exon 7 and trend associations with exon 11. The results provide evidence that the translated polymorphism of exon 7 may be functionally meaningful and impact cortical EEG oscillations. Since variations of EEG coherence have been described for several neuropsychiatric disorders, the present association should be tested in clinical samples using EEG coherence as an intermediate phenotype. © 2003 Wiley‐Liss, Inc.
Defining the autism minimum candidate gene region on chromosome 7
Authors: Hutcheson Holli B. , Bradford Y. , Folstein S.E. , Gardiner M.B. , Santangelo S.L. , Sutcliffe J.S. , Haines J.L. 
Published: January 2003

AbstractPrevious genetic and cytogenetic studies provide evidence that points to one or more autism susceptibility genes residing on chromosome 7q (AUTS1, 115–149 cM on the Marshfield map). However, further localization using linkage analysis has proven difficult. To overcome this problem, we examined the Collaborative Linkage Study of Autism (CLSA) data‐set to identify only the families potentially linked to chromosome 7. Out of 94, 47 families were identified and 17 markers were used to generate chromosomal haplotypes. We performed recombination breakpoint analysis to determine if any portion of the chromosome was predominately shared across families. The most commonly shared region spanned a 6 cM interval between D7S501 and D7S2847. Additional markers at 1 cM intervals within this region were genotyped and association and recombination breakpoint analysis was again performed. Although no significant allelic association was found, the recombination breakpoint data points to a shared region between D7S496–D7S2418 (120–123 cM) encompassing about 4.5 Mb of genomic DNA containing over 50 genes. © 2003 Wiley‐Liss, Inc.
Atypical focal MRI lesions in a case of juvenile Alexander's disease
Authors: Probst Eva Neumaier , Hagel Christian , Weisz Vanja , Nagel Sandra , Wittkugel Oliver , Zeumer Hermann , Kohlschütter Alfried 
Published: January 2003

AbstractWe present a juvenile case of Alexander's disease with atypical focal magnetic resonance imaging–detected lesions and elevated levels of lactate in cerebrospinal fluid. The diagnosis was based on the neuropathological finding of a diffuse accumulation of Rosenthal fibers within the brain and the spinal cord. The diagnosis was confirmed by detection of a mutation in exon 1 at nucleotide position 249 of glial fibrillary acidic protein cDNA, a finding previously reported in cases of infantile Alexander's disease.
Primary progressive aphasia: PPA and the language network
Authors: Sonty Sreepadma P. , Mesulam M.‐Marsel , Thompson Cynthia K. , Johnson Nancy A. , Weintraub Sandra , Parrish Todd B. , Gitelman Darren R. 
Published: January 2003

AbstractPrimary Progressive Aphasia (PPA) is a behaviorally focal dementia syndrome with deterioration of language functions but relative preservation of other cognitive domains for at least the first two years of disease. In this study, PPA patients with impaired word finding but intact comprehension of conversational speech and their matched control subjects were examined using voxel‐based morphometry (VBM) and functional magnetic resonance imaging (fMRI). fMRI compared signal changes during phonological and semantic language tasks with those during a control task (matching letters). PPA patients showed longer reaction times and reduced accuracy versus controls on the language tasks, but no performance differences on the control task. VBM demonstrated reduced gray matter in left superior temporal and inferior parietal regions in the PPA group. However, these patients showed a normal pattern of activation within the classical language regions. In addition, PPA patients showed activations, not seen in normals, in fusiform gyrus, precentral gyrus, and intra‐parietal sulcus. These activations were found to correlate negatively with measures of naming and task performance. The additional activations in PPA may therefore represent a compensatory spread of language‐related neural activity or a failure to suppress activity in areas normally inhibited during language tasks. Ann Neurol 2003;53:000–000
Reduction of P/Q‐type calcium channels in the postmortem cerebellum of paraneoplastic cerebellar degeneration with Lambert‐Eaton myasthenic syndrome
Authors: Fukuda Taku , Motomura Masakatsu , Nakao Yoko , Shiraishi Hirokazu , Yoshimura Toshiro , Iwanaga Keisuke , Tsujihata Mitsuhiro , Dosaka‐Akita Hirotoshi , Eguchi Katsumi 
Published: January 2003

AbstractThe aim of this study was to clarify whether autoimmunity against P/Q‐type voltage‐gated calcium channels (VGCCs) in the cerebellum was associated with the pathogenesis of paraneoplastic cerebellar degeneration (PCD) with Lambert‐Eaton myasthenic syndrome (LEMS). We used human autopsy cerebellar tissues from three PCD‐LEMS patients and six other disease patients including one with LEMS as the controls. We compared cerebellar P/Q‐type VGCC in these patients and controls for the amount and ratio of autoantibody‐channel complex using an 125I‐ω‐conotoxin MVIIC‐binding assay with Scatchard analysis, and their distribution using autoradiography. The quantity of cerebellar P/Q‐type VGCC measured by Scatchard analysis were reduced in PCD‐LEMS patients (63.0 ± 7.0fmol/mg, n = 3), compared with the controls (297.8 ± 38.9fmol/mg, n = 6). The ratio of autoantibody‐VGCC complexes to total P/Q‐type VGCCs measured by immunoprecipitation assay were increased in PCD‐LEMS patients. We analysed cerebellar specimens by autoradiography using 125I‐ω‐conotoxin MVIIC, which specifically binds to P/Q‐type VGCCs. In PCD‐LEMS cerebellum, the toxin binding sites of P/Q‐type VGCCs were markedly reduced compared with controls, especially in the molecular layer, which is the richest area of P/Q‐type VGCCs in the normal cerebellum. This suggests that P/Q‐type VGCCs of the cerebellar molecular layer is the immunological target in developing PCD‐LEMS.
Mechanisms underlying PTEN regulation of vascular endothelial growth factor and angiogenesis
Authors: Gomez‐Manzano Candelaria , Fueyo Juan , Jiang Hong , Glass Tricia L. , Lee Ho‐Young , Hu Min , Liu Juinn‐Lin , Jasti Sushma L. , Liu Ta‐Jen , Conrad Charles A. , Yung W. K. Alfred 
Published: January 2003

AbstractInactivation of the tumor suppressor gene PTEN and overexpression of VEGF are two of the most common events observed in high‐grade malignant gliomas. The purpose of this study was to determine whether PTEN controls VEGF expression in gliomas under normoxic conditions. Transfer of PTEN to human glioma cells resulted in the transduction of a functional PTEN protein as evidenced by the upregulation of p27 and modification of the phosphorylation status of Akt. Under normoxic conditions, enzyme‐linked immunosorbent assay and Northern blot analyses showed downregulation of VEGF in PTEN‐treated cells. Moreover, conditioned media from PTEN‐treated glioma cells significantly diminished the ability of endothelial cells to grow and migrate. Western blot assays demonstrated that, in a normoxic environment, PTEN downregulates HIF‐1α. Finally, promoter activity assays showed that the VEGF promoter region containing the HIF‐1α binding site is necessary and sufficient for PTEN‐mediated downregulation of VEGF. Experiments with PI3‐K inhibitors and kinase assays suggested that PI3‐K is mediating the effect of PTEN on VEGF, and not the p42/p48 or p38 MAP kinases. These results indicate that restoration of PTEN function in gliomas may induce therapeutic effect by downregulating VEGF. Furthermore, this close functional relationship between PTEN and VEGF suggests that a better understanding of the transduction signal regulated by PTEN might enhance the knowledge of the cause and physiology of vascular and inflammatory diseases. Ann Neurol 2003