bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genotype-Environment Interactions of Spontaneous Mutations for Vegetative Fitness in the Human Pathogenic Fungus Cryptococcus neoformans
Authors: Xu Jianping 
Published: December 2004

Abstract
Spontaneous mutation is the ultimate source of all genetic variation. By interacting with environmental factors, genetic variation determines the phenotype and fitness of individuals in natural populations. However, except in a few model organisms, relatively little is known about the patterns of genotype-environment interactions of spontaneous mutations. Here I examine the rates of spontaneous mutation and the patterns of genotype-environment interaction of mutations affecting vegetative growth in the human fungal pathogen Cryptococcus neoformans. Eight mutation accumulation (MA) lines were established from a single clone on the nutrient-rich medium YEPD for each of two temperatures, 25° and 37°. Cells from generations 100, 200, 400, and 600 for each of the 16 MA lines were stored and assayed for vegetative growth rates under each of four conditions: (i) 25° on SD (a synthetic dextrose minimal medium); (ii) 25° on YEPD; (iii) 37° on SD; and (iv) 37° on YEPD. Both MA conditions and assay environments for vegetative growth showed significant influence on the estimates of genomic mutation rates, average effect per mutation, and mutational heritability. Significant genotype-environment interactions were detected among the newly accumulated spontaneous mutations. Overall, clones from MA lines maintained at 37° showed less decline in vegetative fitness than those maintained at 25°. The result suggests that a high-temperature environment might be very important for the maintenance of the ability to grow at a high temperature. Results from comparisons between clinical and environmental samples of C. neoformans were consistent with laboratory experimental population analyses. This study calls into question our long-standing view that warm-blooded mammals were only occasional and accidental hosts of this human fungal pathogen.
Maximum-Likelihood Estimation of Demographic Parameters Using the Frequency Spectrum of Unlinked Single-Nucleotide Polymorphisms
Authors: Adams Alison M , Hudson Richard R 
Published: December 2004

Abstract
A maximum-likelihood method for demographic inference is applied to data sets consisting of the frequency spectrum of unlinked single-nucleotide polymorphisms (SNPs). We use simulation analyses to explore the effect of sample size and number of polymorphic sites on both the power to reject the null hypothesis of constant population size and the properties of two- and three-dimensional maximum-likelihood estimators (MLEs). Large amounts of data are required to produce accurate demographic inferences, particularly for scenarios of recent growth. Properties of the MLEs are highly dependent upon the demographic scenario, as estimates improve with a more ancient time of growth onset and smaller degree of growth. Severe episodes of growth lead to an upward bias in the estimates of the current population size, and that bias increases with the magnitude of growth. One data set of African origin supports a model of mild, ancient growth, and another is compatible with both constant population size and a variety of growth scenarios, rejecting greater than fivefold growth beginning &gt;36,000 years ago. Analysis of a data set of European origin indicates a bottlenecked population history, with an 85% population reduction occurring ∼30,000 years ago.
Gene Deletions by Ends-In Targeting in Drosophila melanogaster
Authors: Xie Heng B , Golic Kent G 
Published: December 2004

Abstract
Following the advent of a gene targeting technique in Drosophila, different methods have been developed to modify the Drosophila genome. The initial demonstration of gene targeting in flies used an ends-in method, which generates a duplication of the target locus. The duplicated locus can then be efficiently reduced to a single copy by generating a double-strand break between the duplicated segments. This method has been used to knock out target genes by introducing point mutations. A derivative of this method is reported here. By using different homologous regions for the targeting and reduction steps, a complete deletion of the target gene can be generated to produce a definitive null allele. The breakpoints of the deletion can be precisely controlled. Unlike ends-out targeting, this method does not leave exogenous sequence at the deleted locus. Three endogenous genes, Sir2, Sirt2, and p53 have been successfully deleted using this method.
A Unified Statistical Model for Functional Mapping of Environment-Dependent Genetic Expression and Genotype × Environment Interactions for Ontogenetic Development
Authors: Zhao Wei , Zhu Jun , Gallo-Meagher Maria , Wu Rongling 
Published: December 2004

AbstractThe effects of quantitative trait loci (QTL) on phenotypic development may depend on the environment (QTL × environment interaction), other QTL (genetic epistasis), or both. In this article, we present a new statistical model for characterizing specific QTL that display environment-dependent genetic expressions and genotype × environment interactions for developmental trajectories. Our model was derived within the maximum-likelihood-based mixture model framework, incorporated by biologically meaningful growth equations and environment-dependent genetic effects of QTL, and implemented with the EM algorithm. With this model, we can characterize the dynamic patterns of genetic effects of QTL governing growth curves and estimate the global effect of the underlying QTL during the course of growth and development. In a real example with rice, our model has successfully detected several QTL that produce differences in their genetic expression between two contrasting environments. These detected QTL cause significant genotype × environment interactions for some fundamental aspects of growth trajectories. The model provides the basis for deciphering the genetic architecture of trait expression adjusted to different biotic and abiotic environments and genetic relationships for growth rates and the timing of life-history events for any organism.
Genetic Analysis of the Caenorhabditis elegans pax-6 Locus
Authors: Cinar Hediye Nese , Chisholm Andrew D 
Published: December 2004

Abstract
PAX-6 proteins are involved in eye and brain development in many animals. In the nematode Caenorhabditis elegans the pax-6 locus encodes multiple PAX-6 isoforms both with and without a paired domain. Mutations in the C. elegans pax-6 locus can be grouped into three classes. Mutations that affect paired domain-containing isoforms cause defects in epidermal morphogenesis, epidermal cell fates, and gonad cell migration and define the class I (vab-3) complementation group. The class II mutation mab-18(bx23) affects nonpaired domain-containing isoforms and transforms the fate of a sensory organ in the male tail. Class III mutations affect both paired domain and nonpaired domain isoforms; the most severe class III mutations are candidate null mutations in pax-6. Class III mutant phenotypes do not resemble a simple sum of class I and class II phenotypes. A comparison of class I and class III phenotypes indicates that PAX-6 isoforms can interact additively, synergistically, or antagonistically, depending on the cellular context.
An Arabidopsis thaliana Plasma Membrane Proton Pump Is Essential for Pollen Development
Authors: Robertson Whitney R , Clark Katherine , Young Jeffery C , Sussman Michael R 
Published: December 2004

Abstract
The plasma membrane proton pump (H+-ATPase) found in plants and fungi is a P-type ATPase with a polypeptide sequence, structure, and in vivo function similar to the mammalian sodium pump (Na+, K+-ATPase). Despite its hypothetical importance for generating and maintaining the proton motive force that energizes the carriers and channels that underlie plant nutrition, genetic evidence for such a central function has not yet been reported. Using a reverse genetic approach for investigating each of the 11 isoforms in the Arabidopsis H+-ATPase (AHA) gene family, we found that one member, AHA3, is essential for pollen formation. A causative role for AHA3 in male gametogenesis was proven by complementation with a normal transgenic gene and rescue of the mutant phenotype back to wild type. We also investigated the requirement for phosphorylation of the penultimate threonine, which is found in most members of the AHA family and is thought to be involved in regulating catalytic activity. We demonstrated that a T948D mutant form of the AHA3 gene rescues the mutant phenotype in knockout AHA3 plants, but T948A does not, providing the first in planta evidence in support of the model in which phosphorylation of this amino acid is essential.
Genetic Interactions of Drosophila melanogaster arrest Reveal Roles for Translational Repressor Bruno in Accumulation of Gurken and Activity of Delta
Authors: Yan Nan , Macdonald Paul M 
Published: December 2004

Abstract
arrest mutants have pleiotropic phenotypes, ranging from an early arrest of oogenesis to irregular embryonic segmentation defects. One function of arrest is in translational repression of oskar mRNA; this biochemical activity is presumed to be involved in other functions of arrest. To identify genes that could provide insight into how arrest contributes to translational repression or that may be targets for arrest-dependent translational control, we screened deficiency mutants for dominant modification of the arrest phenotype. Only four of the many deficiencies tested, which cover ∼30% of the genome, modified the starting phenotype. One enhancer, identified fortuitously, is the Star gene. Star interaction with arrest results in excess Gurken protein, supporting the model that gurken is a target of repression. Two modifiers were mapped to individual genes. One is Lk6, which encodes a protein kinase predicted to regulate the rate-limiting initiation factor eIF4E. The second is Delta. The interaction between arrest and Delta mimics the phenotype of homozygous Delta mutants, suggesting that arrest could positively control Delta activity. Indeed, arrest mutants have significantly reduced levels of Delta protein at the interface of germline and follicle cells.
Expressive language in children with Kabuki syndrome
Authors: Defloor Truus , van Borsel John , Schrander‐Stumpel Constance T.R.M. , Curfs Leopold M.G. 
Published: December 2004

AbstractSince the description of Kabuki syndrome in 1981 over 300 cases from a variety of countries have been reported. Only a limited number of these reports, however, provided data on speech language development. Ghent University Hospital (J. Van Borsel, T. Defloor) and the Department of Clinical Genetics, Academic Hospital Maastricht (C.T.R.M. Schrander‐Stumpel, L.M.G. Curfs) are directing research on the specific nature of communicative development in persons with Kabuki syndrome. The aim of the present study was to delineate the language difficulties in the syndrome. The subjects were six Dutch‐speaking children (three male, three female), with chronological age ranging from 4.4 to 10.6 years (mean = 8.1). Spontaneous speech samples were collected, subjected to a consensus orthographic transcription, and analyzed by means of TOAST [Moerman‐Coetsier and Van Besien, 1987], a Dutch standardized diagnostic instrument to investigate different aspects of spontaneous language production. In all the children, expressive language abilities were impaired. Poor morphosyntactic abilities were consistently demonstrated. Lexical and pragmatic difficulties were also present, whereas phonological development was less often affected. © 2004 Wiley‐Liss, Inc.
Supernumerary ring chromosome 7 mosaicism: Case report, investigation of the gene content, and delineation of the phenotype
Authors: Lichtenbelt K.D. , Hochstenbach R. , van Dam W.M. , Eleveld M.J. , Poot M. , Beemer F.A. 
Published: December 2004

AbstractWe report a girl with severe retardation of expressive speech development carrying a small, supernumerary ring chromosome derived from the proximal region of the long arm of chromosome 7. The r(7) chromosome is present in 50% of lymphocytes. We also review the six additional cases with a supernumerary r(7) chromosome reported in the literature. Among these patients, a severe retardation of productive language capabilities is seen as a shared clinical feature, irrespective of the degree of mosaicism as detected in blood. The dysmorphisms in these patients are minor and no shared congenital abnormalities seen. We, therefore, recommend chromosomal investigations in children with unexplained, disproportionately retarded expressive speech performance. Because speech and language acquisition are subject to genetic influences, we investigated whether there are genes on the r(7) chromosome that may affect brain development or function in a dosage‐dependent manner. We found that both in our patient and in four patients described by others, the supernumerary r(7) chromosome contains the region from the centromere up to marker D7S613 located at 7q11.23. We speculate that the effects on speech acquisition are mediated by the supernumerary copies of the STX1A and LIMK1 genes, which are both located in this region and known to suppress neurite growth when overexpressed in vitro. © 2004 Wiley‐Liss, Inc.
Kabuki syndrome is not caused by an 8p duplication: A cytogenetic study in 20 patients
Authors: Engelen John J.M. , Loneus Wim H. , Vaes‐Peeters Gerrie , Schrander‐Stumpel Constance T.R.M. 
Published: December 2004

AbstractKabuki syndrome is charcterized by a typical facial gestalt in combination with hypotonia and joint laxity, developmental delay, persistent fetal fingertip pads, and structural abnormalities mainly of the palate and the heart. Cytogenetic conditions may present with features of the syndrome. Recently, Milunsky and Huang [2003], reported an 8p duplication at chromosome 8p22‐8p23.1 in 6 patients with Kabuki syndrome. We studied 20 individuals with Kabuki syndrome and were not able to confirm this finding. Kabuki syndrome remains a clinical diagnosis in the majority of cases. © 2004 Wiley‐Liss, Inc.
Fine mapping of a region on chromosome 8p gives evidence for a QTL contributing to individual differences in an anxiety‐related personality trait: TPQ harm avoidance
Authors: Dina Christian , Nemanov Lubov , Gritsenko Inga , Rosolio Naama , Osher Yamima , Heresco‐Levy Uri , Sariashvilli Emma , Bachner‐Melman Rachel , Zohar Ada H. , Benjamin Jonathan , Belmaker Robert H. , Ebstein Richard P. 
Published: December 2004

AbstractThe chromosome 8p region is of interest in human behavioral genetics since it harbors a susceptibility region not only for schizophrenia but also for anxiety‐related personality traits such as harm avoidance and neuroticism. Towards verifying our preliminary linkage finding of a QTL for TPQ harm avoidance at chromosome 8p, we have now genotyped altogether 24 micro‐satellite markers in 377 families. Using three methods (maximum likelihood binomial or MLB, MERLIN, and an associated one parameter model), we observed significant results (P values from 0.002 to 0.0004) for linkage to harm avoidance in this region. A peak multipoint LOD score of 2.76 (P value 0.0002) was obtained with the MLB method. The region‐wide empirical P value was 0.002 [0.001–0.0046]. Although, the peak position varied somewhat according to the method (D8S1048 for MLB, D8S1463 for the two other methods), for three methods D8S1810 (∼60 cM) is within 1–2 cM of the peak for harm avoidance. This marker is of particular interest since it is proximate (<0.5 cM) of the core haplotype that in several recent studies show significant association with schizophrenia near neuroregulin 1. Although association studies with microsatellite markers need to be interpreted cautiously, using the Haplotype Trend Regression test one marker, D8S499 (∼60 cM), showed an empirical P value of 2 × 10−5 for allele 3, which confers a decreased harm avoidance score. Altogether, the current linkage and association results suggest the possibility that the same locus near the neuroregulin 1 gene on chromosome 8p confers risk for both an anxiety‐related personality trait as well as schizophrenia. We hypothesize that this common genetic factor may contribute to emotional liability during early development, which constitutes a predisposing factor for major psychosis. © 2004 Wiley‐Liss, Inc.
Quantitative trait locus analysis of candidate gene alleles associated with attention deficit hyperactivity disorder (ADHD) in five genes: DRD4, DAT1, DRD5, SNAP‐25, and 5HT1B
Authors: Mill Jonathan , Xu Xiaohui , Ronald Angelica , Curran Sarah , Price Tom , Knight Jo , Craig Ian , Sham Pak , Plomin Robert , Asherson Philip 
Published: December 2004

AbstractIt has been widely postulated that the categorical diagnosis of attention deficit hyperactivity disorder (ADHD) should be seen as the extreme end of a set of traits quantitatively distributed in the general population. A consequence of this is that the genes associated with DSM‐IV ADHD should also influence these underlying traits in non‐affected individuals. The aim of this study was to examine if specific candidate loci previously shown to be associated with DSM‐IV ADHD, also act as quantitative trait loci (QTLs) for ADHD‐symptoms in the general population. We have genotyped five candidate markers in a population‐based sample of male dizygous twin‐pairs (n = 329 pairs). We found little evidence to support a role for the previously‐nominated alleles of a DRD4 VNTR, a 5HT1B SNP, or a microsatellite marker near to DRD5, in the distribution of ADHD‐symptoms scores; however, we found some evidence to suggest that the DAT1 3′UTR VNTR and weak evidence that a microsatellite in SNAP‐25 may have a role in continuous measures of ADHD‐symptoms hyperactivity above and beyond their role in clinical ADHD. © 2004 Wiley‐Liss, Inc.
The 3111T/C polymorphism of hClock is associated with evening preference and delayed sleep timing in a Japanese population sample
Authors: Mishima Kazuo , Tozawa Takuma , Satoh Kohtoku , Saitoh Hidetomo , Mishima Yumiko 
Published: December 2004

AbstractSleep timing is influenced by the circadian system. Morningness‐eveningness (ME) preference in humans is affected by the free‐running period, which is determined by circadian clock‐relevant genes. In this study, we investigated association between the 3111T/C polymorphism in the 3′‐flanking region of hClock (Homo sapiens Clock homolog) and ME preference in 421 Japanese subjects. The Horne–Ostberg ME questionnaire (MEQ) scores showed normal distribution, with mean score of 51.2 ± 1.4 (range, 25–73), and scores were positively correlated with sleep onset time (r = 0.541, P < 0.001) and wake time (r = 0.513, P < 0.001). MEQ scores were significantly lower in subjects with 3111C/C (n = 12) than in subjects with 3111T/C (n = 106, P < 0.001) or 3111T/T (n = 303, P < 0.001), suggesting a stronger eveningness preference in 3111C/C homozygotes. This group also showed significantly delayed sleep onset (P < 0.001), shorter sleep time (P < 0.001), and greater daytime sleepiness (P < 0.001) in comparison to parameters in the subjects with the 3111T allele. There was no significant difference in any of these parameters between the 3111C/T and 3111T/T genotypes. The influence of the 3111T/C polymorphism on ME preferences in Caucasian populations remains controversial. The present findings in a Japanese population sample, which should have a relatively low risk of population stratification effects, suggest the significance of the association of the 3111C/C allele of hClock with evening preference. © 2004 Wiley‐Liss, Inc.
Dopamine receptor D4 (DRD4) gene in Han Chinese children with attention‐deficit/hyperactivity disorder (ADHD): Increased prevalence of the 2‐repeat allele
Authors: Leung Patrick W.L. , Lee C.C. , Hung S.F. , Ho T.P. , Tang C.P. , Kwong S.L. , Leung S.Y. , Yuen S.T. , Lieh‐Mak F. , Oosterlaan Jaap , Grady Deborah , Harxhi Ante , Ding Y.C. , Chi H.C. , Flodman Pamela , Schuck Sabrina , Spence M. Anne , Moyzis Robert , Swanson James 
Published: December 2004

AbstractThere is an increased prevalence of the 7‐repeat (7R) allele of the dopamine receptor D4 (DRD4) gene in attention‐deficit/hyperactivity disorder (ADHD). However, the population prevalence of the 7R allele varies considerably across ethnicity and is very low in Asians. To test whether this 7R allele/ADHD association still held in a Chinese clinical sample, 32 Han Chinese children with a confirmed ADHD diagnosis and normal IQ who were methylphenidate‐responders were genotyped. None of them had a DRD4 7R allele. Instead, we observed a significantly increased prevalence of the 2‐repeat (2R) allele in this clinical sample (33%) compared to ethnically‐matched controls (20%) (χ2(1d.f.) = 5.90, P = 0.015). This approximately 1.65‐fold increase of the 2R allele in our probands is close to the observed increase of the 7R allele in European‐ancestry ADHD children. Recent genetic studies have indicated that the 2R allele in Asians is likely derived from the 7R allele. Further, available biochemical data indicate that both the 2R and 7R protein have blunted responses to dopamine compared to the 4R protein. Based on these results, we propose that the observed increased prevalence of the 2R allele in our Han Chinese ADHD probands is still consistent with the 7R allele hypothesis of ADHD in European‐ancestry children. Recent studies have suggested that any variant from the conserved ancestral 4R allele might potentially alter biochemistry/phenotype. We hypothesize that an increased frequency of any non‐4R allele may define the association of the DRD4 gene with ADHD that holds across ethnicity. The present findings, however, obtained with a small ADHD sample size, should be replicated. © 2004 Wiley‐Liss, Inc.
A flexible interface design for Web directories to accommodate different cognitive styles
Authors: Chen Sherry Y. , Magoulas George D. , Dimakopoulos Dionisios 
Published: December 2004

AbstractSearch engines are very popular tools for collecting information from distributed resources. They provide not only search facilities, but they also offer directories for users to browse content divided into groups. In this paper, we've adopted an individual differences approach to explore user's attitudes towards various interface features provided by existing Web directories. Among a variety of individual differences, cognitive style is a particularly important characteristic that influences the effectiveness of information seeking. Empirical results indicate that users' cognitive styles influence their reactions to the organization of subject categories, presentation of the results, and screen layout. We developed a set of design guidelines on the basis of these results, and propose a flexible interface that adopts these guidelines to accommodate the preferences of different cognitive style groups.