bluuebunny/crossref_metadata_2025_split huggingface dataset:
Different mutations in theNF1gene are associated with Neurofibromatosis–Noonan syndrome (NFNS)
Authors: Baralle Diana , Mattocks Chris , Kalidas Kamini , Elmslie Frances , Whittaker Joanne , Lees Melissa , Ragge Nicola , Patton Michael A. , Winter Robin M. , ffrench‐Constant Charles 
Published: April 2003

AbstractThe association of the Noonan phenotype with neurofibromatosis type 1 (NF1) was first noted by Allanson et al. [Am J Med Genet 1985;21:457–462.] and 30 further cases have subsequently been reported. It has been suggested that this phenotype is more common than previously appreciated, as Colley et al. [Clin Genet 1996;49:59–64.] examined 94 sequentially identified patients with NF1 from their genetic register and found Noonan features in 12. A 3‐bp deletion of exon 17 of theNF1neurofibromin gene was described in one family by Carey et al. [Proc Greenwood Genet Center 1997;17:52–53]. However, it remains unclear whether Neurofibromatosis–Noonan syndrome (NFNS) represents a form of NF1 (with mutations in theNF1neurofibromin gene) or a separate syndrome. We have used a new, rapid sequence analysis technique—comparative sequence analysis (CSA)—to examine theNF1gene in six patients with NFNS. None of the six patients had the previously identified mutation, nor did we observe other mutations within this exon. However, two other mutations were found: in exon 25, a 3‐bp deletion 4312 del GAA, and in exon 23‐2, a 2‐bp insertion 4095 ins TG. ThePTPN11gene, now known to cause over 50% of Noonan syndrome was also examined in four cases of NFNS, and no mutations were found. These results show that NFNS can in some cases result from different mutations in theNF1gene and therefore represents a variant form of NF1. © 2003 Wiley‐Liss, Inc.
High resolution mapping and mutation analyses of candidate genes in the urofacial syndrome (UFS) critical region
Authors: Wang Cong‐Yi , Davoodi‐Semiromi Abodoreza , Shi Jing‐Da , Yang Ping , Huang Yi‐Qun , Agundez Jose A. G. , Moran Jose M. , Ochoa Bernardo , Hawkins‐Lee Bobbilynn , She Jin‐Xiong 
Published: April 2003

AbstractThe urofacial (Ochoa) syndrome (UFS) characterized by congenital obstructive uropathy and abnormal facial expression is a rare disorder caused by a single recessive disease gene. Our previous studies using homozygosity mapping have located the UFS gene to a genomic interval of approximately 360 kb on chromosome 10q23‐10q24. In this study, we have constructed a genomic sequence map covering the entire UFS interval and narrowed the disease interval to a genomic region of 220 kb that harbor the newly identified ACDP1 gene in addition to part of the GOT1 gene which has already been excluded as a candidate for UFS. Extensive search for mutations in the coding region, the 5′ and 3′ untranslated regions, the promoter region, and the exon/intron junctions failed to identify a pathogenic mutation in UFS patients. Furthermore, our analyses indicated that the same gene on chromosome 10q is responsible for all UFS patients from multiple ethnic groups. © 2003 Wiley‐Liss, Inc.
Specific BACE1 genotypes provide additional risk for late‐onset alzheimer disease in APOE ε4 carriers
Authors: Gold Gabriel , Blouin Jean‐Louis , Herrmann François R. , Michon Agnès , Mulligan Reinhild , Duriaux Saïl Geneviève , Bouras Constantin , Giannakopoulos Panteleimon , Antonarakis Stylianos E. 
Published: April 2003

AbstractAlzheimer disease (AD) is characterized neuropathologically by neurofibrillary tangles and senile plaques. A key component of plaques is Aβ, a polypeptide derived from Aβ‐precursor protein (APP) through proteolytic cleavage catalyzed by β and γ‐secretase. We hypothesized that sequence variation in genes BACE1 (on chromosome 11q23.3) and BACE2 (on chromosome 21q22.3), which encode two closely related proteases that seem to act as the APP β‐secretase, may represent a genetic risk factor for AD. We analyzed the frequencies of single nucleotide polymorphisms (SNPs) in BACE1 and BACE2 genes in a community‐based sample of 96 individuals with late‐onset AD and 170 controls selected randomly among residents of the same community. The genotype data in both study groups did not demonstrate any association between AD and BACE1 or BACE2. After stratification for APOE status, however, an association between a BACE1 polymorphism located within codon V262 and AD in APOE ε4 carriers was observed (P = 0.03). We conclude that sequence variation in the BACE1 or BACE 2 gene is not a significant risk factor for AD; however, a combination of a specific BACE1 allele and APOE ε4 may increase the risk for Alzheimer disease over and above that attributed to APOE ε4 alone. © 2003 Wiley‐Liss, Inc.
5HTTLPR polymorphism in schizophrenic patients: Further support for association with violent suicide attempts
Authors: Bayle F.J. , Leroy S. , Gourion D. , Millet B. , Olié J.P. , Poirier M.F. , Krebs M.O. 
Published: April 2003

AbstractPrevious studies testing the functional polymorphism in the promoter of the serotonin‐transporter gene (5HTTLPR) in various psychiatric conditions have suggested that the association could be with an intermediate phenotype, impulsivity and/or violence rather than with a diagnosis. Schizophrenia is associated with a high risk of suicide, especially in patients with high impulsivity. We examined whether this polymorphism could be associated with violent suicide and/or impulsivity in schizophrenic patients. We genotyped the 5HTTLPR polymorphism in 185 unrelated schizophrenic patients from a French Caucasian population. The genotype frequencies significantly differed between patients who made violent suicide attempts and both, those who attempted suicide with a non‐violent method (P = 0.013) and those who never attempted suicide (P = 0.026). The genotypes containing the low activity “short” allele was significantly more frequent in violent suicide attempters (P = 0.007) than in non‐violent suicide attempters. No evidence was found for an association either with schizophrenia itself, when compared to gender and ethnically matched controls (n = 159) or with impulsivity, assessed using Barratt's Impulsivity Scale. Although replication studies are warranted, these results in schizophrenia further support the hypothesis that 5HTTLPR polymorphism is a risk factor for violent suicidal behavior. © 2003 Wiley‐Liss, Inc.
Genetic heterogeneity in a very large bipolar affective disorder pedigree from Quebec
Authors: Shink E. , Morissette J. , Barden N. 
Published: April 2003

AbstractWe previously reported a genome‐wide scan for bipolar affective disorder based on a multigenerational family sampled from a relatively homogeneous population derived from founding families that migrated to an isolated area of Quebec from the early 1830s onwards. For the genome scan, the pedigree was split into five branches to facilitate calculation and a second family was added to more specifically analyze chromosome 12 results. In the present study, we reanalyzed the undivided pedigree after genealogical links were reconstructed over ten generations to investigate a founder effect using an algorithm in the SIMWALK2 package. Our results do not lend support to the presence of a common haplotype shared among affected individuals. © 2003 Wiley‐Liss, Inc.
Severe myoclonus‐dystonia syndrome associated with a novel epsilon‐sarcoglycan gene truncating mutation
Authors: Maréchal Lucie , Raux Grégory , Dumanchin Cécile , Lefebvre Guillaume , Deslandre Emmanuelle , Girard Carole , Campion Dominique , Parain Dominique , Frebourg Thierry , Hannequin Didier 
Published: April 2003

AbstractMyoclonus‐dystonia syndrome (MDS) is an autosomal dominant disorder characterized by myoclonic and dystonic muscle contractions, associated with psychiatric manifestations. MDS is usually considered as a benign disease. In most of the families, MDS is linked to chromosome 7q21 and mutations within epsilon‐sarcoglycan (SGCE) gene have been recently described. We report a MDS family with a severe and heterogeneous phenotype, including myoclonus with important functional impact and several psychiatric features, characterized by obsessive‐compulsive disorder, depression, and anxiety. This phenotype was shown to be associated with a novel truncating mutation located within exon 4 of SGCE. © 2003 Wiley‐Liss, Inc.
Genome scan of a second wave of NIMH genetics initiative bipolar pedigrees: chromosomes 2, 11, 13, 14, and X
Authors: Zandi Peter P. , Willour Virginia L. , Huo Yuqing , Chellis Jennifer , Potash James B. , MacKinnon Dean F. , Simpson Sylvia G. , McMahon Francis J. , Gershon Elliot , Reich Theodore , Foroud Tatiana , Nurnberger John , DePaulo J. Raymond , McInnis Melvin G. 
Published: April 2003

AbstractAs part of the on‐going NIMH Genetics Initiative on Bipolar Disorder, we have ascertained 153 multiplex bipolar pedigrees and genotyped them in two waves. We report here the genome scan results for chromosomes 2, 11, 13, 14, and X in the second wave of 56 families. A total of 354 individuals were genotyped and included in the current analyses, including 5 with schizoaffective/bipolar (SA/BP), 139 with bipolar I disorder (BPI), 41 with bipolar II disorder (BPII), and 43 with recurrent unipolar depression (RUP). Linkage analyses were carried out with multi‐point parametric and non‐parametric affected relative pair methods using three different definitions of the affected phenotype: (model 1) SA/BP and BPI; (model 2) SA/BP, BPI, and BPII; and (model 3) SA/BP, BPI, BPII, and RUP. The best findings were on 11p15.5 (NPL = 2.96, P = 0.002) and Xp11.3 (NPL = 2.19, P = 0.01). These findings did not reach conventional criteria for significance, but they were located near regions that have been identified in previous genetic studies of bipolar disorder. The relatively modest but consistent findings across studies may suggest that these loci harbor susceptibility genes of modest effect in a subset of families. Large samples such as that being collected by the NIMH Initiative will be necessary to examine the heterogeneity and identify these susceptibility genes. © 2003 Wiley‐Liss, Inc.
Depression in Alzheimer's disease: The effect of serotonin receptor gene variation
Authors: Holmes Clive , Arranz Maria , Collier David , Powell John , Lovestone Simon 
Published: April 2003

AbstractThis study investigated possible associations between selected polymorphisms in the serotonin receptor genes, 5‐HT2A and 5‐HT2C, with the presence of co‐morbid depressive illness at baseline in a community based cohort of 158 patients with late onset patients with Alzheimer's disease (AD). An association was found between the presence of major depressive illness at baseline and both the 5‐HT2A and 5‐HT2C polymorphisms. Specifically, homozygous carriers of the 5‐HT2A C102 allele were five times more likely to have major depressive illness than heterozygotes. In addition, homozygous or hemizygous carriers of the 5‐HT2C Ser allele were 12 times more likely to have major depressive illness than homozygous or hemizygous carriers of the 5‐HT2C Cys allele. © 2003 Wiley‐Liss, Inc.
Apolipoprotein E in schizophrenia: A French association study and meta‐analysis
Authors: Schürhoff Franck , Krebs Marie‐Odile , Szöke Andrei , Loze Jean‐Yves , Goldberger Céline , Quignon Valérie , Tignol Jean , Rouillon Frédéric , Laplanche Jean‐Louis , Leboyer Marion 
Published: April 2003

AbstractSchizophrenic disorders are complex genetic disorders that may involve multiple genes of small effect. Apolipoprotein E (ApoE) gene variants are associated with alterations in brain function and an increased risk of Alzheimer's disease (AD). However, conflicting results have been reported in schizophrenia. We compared the ApoE genotypes of 114 French Caucasian schizophrenic patients and 91 normal controls. No differences in ApoE allele or genotype frequencies were observed between the two groups. However, we observed a possible association between male schizophrenic patients and the ApoE ε2ε3 genotype. In addition, a meta‐analysis of all published case‐control studies on ApoE and schizophrenia did not support a major role for ApoE gene variants in schizophrenia as a whole. However, ApoE may be associated with particular forms of schizophrenia. © 2003 Wiley‐Liss, Inc.
Reduced expression of the muscarinic 1 receptor cortical subtype in schizophrenia
Authors: Mancama D. , Arranz MJ. , Landau S. , Kerwin R. 
Published: April 2003

AbstractThe involvement of specific pathways mediated through muscarinic receptor activity has been widely implicated in schizophrenia. Extensive pharmacological evidence supports the systems role in mediating antipsychotic drug efficacy, while mounting physiological evidence demonstrates the presence of significant alterations to normal muscarinic receptor integrity in the disorder. The mechanisms that facilitate the systems involvement and their magnitude, however, remain poorly understood. We have proposed that alterations to normal muscarinic receptor expression exist in schizophrenia, and that these significantly influence the physiological changes often reported for the system amongst patients. In this study, we investigate this potential, and have selected to examine the muscarinic 1 receptor, which constitutes a major target for antipsychotic action and plays a conspicuous role in those regions central to the disorders pathophysiology. Using relative gene quantification, we measured post‐mortem levels of steady‐state cortical muscarinic 1 receptor cDNA in patients (N = 20) and unaffected controls (N = 20), and examined group differences in expression levels. Commensurate with our hypothesis, we observed significant reductions in muscarinic 1 receptor cDNA in our patient sample (F(1,37) = 4.73, P = 0.036) and have estimated this to constitute a 28% decrease compared to the control subjects (95% CI from 2 to 47%). These results provide evidence in support of altered muscarinic 1 receptor expression in schizophrenia, though further work is needed to corroborate these findings. © 2003 Wiley‐Liss, Inc.
Nanotechnologie mit weichen Materialien
Authors: Hamley I. W. 
Published: April 2003

AbstractDie Natur nutzt die Selbstorganisation weicher Materialien auf vielfache Weise, um Zellmembranen, Biopolymerfasern oder Viren aufzubauen. Auch der Mensch ist seit kurzem in der Lage, Materialien im Nanomaßstab zu entwickeln, entweder durch Steuerung auf atomarer oder molekularer Ebene (Top‐Down) oder durch Selbstorganisation (Bottom‐Up). Die Selbstorganisation weicher Materialien kann genutzt werden, um vielfältige Nanostrukturen für die verschiedensten Anwendungen herzustellen. Die Vielfalt der Strukturen erklärt sich aus den schwachen Ordnungen, die wiederum auf nichtkovalenten Wechselwirkungen beruhen. Damit kommt der thermischen Energie eine besondere Bedeutung zu, da sie Übergänge zwischen Phasen mit unterschiedlichen Ordnungen ermöglicht. Die Stärken der Selbstorganisation lassen sich für die Herstellung von Nanopartikeln und ‐strukturen, der Entwicklung von Nanomotoren, der Nutzung der Biomineralisation bis hin zur Entwicklung funktionalisierter Übertragungsvektoren nutzen.
A Comparison of Procedures for Adaptive Choice of Location Tests in Flexible Two‐Stage Designs
Authors: Friede Tim , Kieser Meinhard , Neuhäuser Markus , Büning Herbert 
Published: April 2003

AbstractAlthough linear rank statistics for the two‐sample problem are distribution free tests, their power depends on the distribution of the data. In the planning phase of an experiment, researchers are often uncertain about the shape of this distribution and so the choice of test statistic for the analysis and the determination of the required sample size are based on vague information. Adaptive designs with interim analysis can potentially overcome both problems. And in particular, adaptive tests based on a selector statistic are a solution to the first. We investigate whether adaptive tests can be usefully implemented in flexible two‐stage designs to gain power. In a simulation study, we compare several methods for choosing a test statistic for the second stage of an adaptive design based on interim data with the procedure that applies adaptive tests in both stages. We find that the latter is a sensible approach that leads to the best results in most situations considered here. The different methods are illustrated using a clinical trial example.
Pairwise Comparisons in Each of Several Groups with Heterogenous Group Variances
Authors: Cheung S.H. , Wu K.H. , Quek A.L. 
Published: April 2003

AbstractPairwise comparison procedures are frequently applied to analyze experimental results. In particular, practitioners in the area of medical researches often encounter situations which require these statistical techniques to compare various treatments. In this article, we focus on pairwise comparison procedures in a two‐factor design, where comparisons of one factor are made simultaneously for each level of another factor. For example, several new drugs to treat a certain cancer are being compared for both male and female patients. Previous research efforts were mainly devoted to models with homogeneous variances. The current paper is to address more common scenario where group variances are heterogeneous.
Simple circuit to improve electric field homogeneity in contour‐clamped homogeneous electric field chambers
Authors: Herrera José A. , Canino Carlos A. , López‐Cánovas Lilia , Gigato Regnar , Riverón Ana Maria 
Published: April 2003

AbstractWe redesigned contour‐clamped homogeneous electric field (CHEF) circuitry to eliminate crossover distortion, to set identical potentials at electrodes of each equipotential pair and to drive pairs with transistors in emitter follower stages. An equipotential pair comprised the two electrodes set at the same potential to provide electric field homogeneity inside of the hexagonal array. The new circuitry consisted of two identical circuits, each having a resistor ladder, diodes and transistors. Both circuits were interconnected by diodes that controlled the current flow to electrodes when the array was energized in the ‘A’ or ‘B’ direction of the electric field. The total number of transistors was two‐thirds of the total number of electrodes. Average voltage deviation from potentials expected at electrodes to achieve a homogeneous electric field was 0.06 V, whereas 0.44 V was obtained with another circuit that used transistors in push‐pull stages. The new voltage clamp unit is cheap, generated homogeneous electric field, and gave reproducible and undistorted DNA band patterns.
High levels of mitochondrial DNA heteroplasmy in single hair roots: Reanalysis and revision
Authors: Grzybowski Tomasz , Malyarchuk Boris A. , Czarny Jakub , Miścicka‐Śliwka Danuta , Kotzbach Roman 
Published: April 2003

AbstractThe present study demonstrates a reinvestigation of the mitochondrial DNA sequence heteroplasmy, which was previously found by the use of nested polymerase chain reaction (PCR) technique in single hairs of 13 individuals. The direct PCR approach was used for the amplification of mitochondrial DNA and a phylogenetic analysis was applied to both data sets for the verification of the authenticity of sequences. The comparative analysis of the sequencing results obtained from the same hair DNA extracts – but using two different techniques – shows that direct mitochondrial DNA amplification results in a considerably lower number of mixed positions. The majority of the confirmed heteroplasmic variants preferentially occurs in mitochondrial DNA hypervariable sites (mutational hotspots). However, the pattern of heteroplasmic mutations observed in four extracts after nested PCR significantly differs from the pattern of natural mutations. Some of these rare polymorphisms should be revised as inconsistent with phylogenetic expectations. The results of the present study contribute to the earlier reports by indicating that phylogenetic analysis is an effective tool in a posteriori quality check of mitochondrial DNA data.
Formation of a resistive region at the anode end in DNA capillary electrophoresis
Authors: Bilenko Olga , Gavrilov Dmitri , Gorbovitski Boris , Gorfinkel Vera , Gouzman Michael , Gudkov Georgy , Khozikov Vyacheslav , Khozikov Olga , Kosobokova Olga , Lifshitz Nadia , Luryi Serge , Stepoukhovitch Andrew , Tcherevishinick Marina , Tyshko Georgy 
Published: April 2003

AbstractWe have studied the formation of a resistive region in the capillary during DNA separation. This effect is caused by an unequal change in the mobilities of cations and anions at the interface between the running buffer solution and the capillary. We studied the motion of the resistive region boundary by sequential removal of portions of the affected capillary end. We found that in the process of developing the resistive region the distribution of the electric fields in the capillary changes from uniform to extremely nonuniform, with a very high field (above 1 MV/cm) in the resistive region and a reduced field (80 V/cm) in the rest of the capillary. Though theoretically a resistive region may appear either at the anode (detection) or the cathode (injection) end of the capillary, all previous publications report the formation of the resistive region at the cathode side. In our experiments, however, the anomalous region is formed at the anode. Thus, the separated DNA peaks move towards the slowly progressing resistive region. Our results indicate that the DNA is stopped at the boundary and does not enter the region. When the resistive region is clipped off the peak motion resumes. This suggests that there exists a potential barrier at the resistive layer boundary that prevents the drift of the peaks towards the anode. The formation of the resistive region interferes with a normal separation process causing a gradual decrease of the capillary current and the deceleration and eventual quenching of the peak motion. For the ABI chemistry, we experimented with adding polymers to the electrode buffer to equate the transference numbers for anions and cations, and found the conditions at which this effect is completely eliminated.
Dynamic range of fluorescence detection and base‐calling accuracy in DNA sequencer based on single‐photon counting
Authors: Gavrilov Dmitri N. , Gorbovitski Boris , Gouzman Mikhail , Gudkov Georgiy , Stepoukhovitch Andrei , Ruskovoloshin Victor , Tsuprik Andrei , Tyshko Georgiy , Bilenko Olga , Kosobokova Olga , Luryi Serge , Gorfinkel Vera 
Published: April 2003

AbstractRecently, we developed a family of high‐performance automated capillary DNA sequencing instruments based on a single‐photon detection of fluorescently labeled DNA fragments. Our machines employ digital and broadband techniques, essential for achieving superior instrument sensitivity and dynamic range. In the present paper, we discuss limitations of the instrument's performance caused by the nonlinearity of single‐photon detectors as well as methods for nonlinearity compensation which increase the detection dynamic range and base‐calling accuracy.