bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dpb2p, a Noncatalytic Subunit of DNA Polymerase ε, Contributes to the Fidelity of DNA Replication in Saccharomyces cerevisiae
Authors: Jaszczur Malgorzata , Flis Krzysztof , Rudzka Justyna , Kraszewska Joanna , Budd Martin E , Polaczek Piotr , Campbell Judith L , Jonczyk Piotr , Fijalkowska Iwona J 
Published: February 2008

Abstract
Most replicases are multi-subunit complexes. DNA polymerase epsilon from Saccharomyces cerevisiae is composed of four subunits: Pol2p, Dpb2p, Dpb3p, and Dpb4p. Pol2p and Dpb2p are essential. To investigate a possible role for the Dpb2p subunit in maintaining the fidelity of DNA replication, we isolated temperature-sensitive mutants in the DPB2 gene. Several of the newly isolated dpb2 alleles are strong mutators, exhibiting mutation rates equivalent to pol2 mutants defective in the 3′ → 5′ proofreading exonuclease (pol2-4) or to mutants defective in mismatch repair (msh6). The dpb2 pol2-4 and dpb2 msh6 double mutants show a synergistic increase in mutation rate, indicating that the mutations arising in the dpb2 mutants are due to DNA replication errors normally corrected by mismatch repair. The dpb2 mutations decrease the affinity of Dpb2p for the Pol2p subunit as measured by two-hybrid analysis, providing a possible mechanistic explanation for the loss of high-fidelity synthesis. Our results show that DNA polymerase subunits other than those housing the DNA polymerase and 3′ → 5′ exonuclease are essential in controlling the level of spontaneous mutagenesis and genetic stability in yeast cells.
Major Quantitative Trait Loci Affect Resistance to Infectious Pancreatic Necrosis in Atlantic Salmon (Salmo salar)
Authors: Houston Ross D , Haley Chris S , Hamilton Alastair , Guy Derrick R , Tinch Alan E , Taggart John B , McAndrew Brendan J , Bishop Stephen C 
Published: February 2008

AbstractInfectious pancreatic necrosis (IPN) is a viral disease currently presenting a major problem in the production of Atlantic salmon (Salmon salar). IPN can cause significant mortality to salmon fry within freshwater hatcheries and to smolts following transfer to seawater, although challenged populations show clear genetic variation in resistance. To determine whether this genetic variation includes loci of major effect, a genomewide quantitative trait loci (QTL) scan was performed within 10 full-sib families that had received a natural seawater IPN challenge. To utilize the large difference between Atlantic salmon male and female recombination rates, a two-stage mapping strategy was employed. Initially, a sire-based QTL analysis was used to detect linkage groups with significant effects on IPN resistance, using two to three microsatellite markers per linkage group. A dam-based analysis with additional markers was then used to confirm and position any detected QTL. Two genomewide significant QTL and one suggestive QTL were detected in the genome scan. The most significant QTL was mapped to linkage group 21 and was significant at the genomewide level in both the sire and the dam-based analyses. The identified QTL can be applied in marker-assisted selection programs to improve the resistance of salmon to IPN and reduce disease-related mortality.
Interplay of Developmentally Regulated Gene Expression and Heterochromatic Silencing in Trans in Drosophila
Authors: Sage Brian T , Wu Michael D , Csink Amy K 
Published: February 2008

Abstract
The brownDominant (bwD) allele of Drosophila contains a heterochromatic block that causes the locus to interact with centric heterochromatin. This association silences bw+ in heterozygotes (trans-inactivation) and is dependent on nuclear organizational changes later in development, suggesting that trans-inactivation may not be possible until later in development. To study this, a P element containing an upstream activating sequence (UAS)–GFP reporter was inserted 5 kb from the bwD insertion site. Seven different GAL4 driver lines were used and GFP fluorescence was compared in the presence or the absence of bwD. We measured silencing in different tissues and stages of development and found variable silencing of GFP expression driven by the same driver. When UAS–GFP was not expressed until differentiation in the eye imaginal disc it was more easily trans-inactivated than when it was expressed earlier in undifferentiated cells. In contrast to some studies by other workers on silencing in cis, we did not find consistent correlation of silencing with level of expression or evidence of relaxation of silencing with terminal differentiation. We suggest that such contrasting results may be attributed to a potentially different role played by nuclear organization in cis and trans position-effect variegation.
The Molecular Basis of Host Adaptation in Cactophilic Drosophila: Molecular Evolution of a GlutathioneS-Transferase Gene (GstD1) inDrosophila mojavensis
Authors: Matzkin Luciano M 
Published: February 2008

AbstractDrosophila mojavensis is a cactophilic fly endemic to the northwestern deserts of North America. This species includes four genetically isolated cactus host races each individually specializing on the necrotic tissues of a different cactus species. The necrosis of each cactus species provides the resident D. mojavensis populations with a distinct chemical environment. A previous investigation of the role of transcriptional variation in the adaptation of D. mojavensis to its hosts produced a set of candidate loci that are differentially expressed in response to host shifts, and among them was glutathione S-transferase D1 (GstD1). In both D. melanogaster and Anopheles gambiae, GstD1 has been implicated in the resistance of these species to the insecticide dichloro-diphenyl-trichloroethane (DDT). The pattern of sequence variation of the GstD1 locus from all four D. mojavensis populations, D. arizonae (sister species), and D. navojoa (outgroup) has been examined. The data suggest that in two populations of D. mojavensis GstD1 has gone through a period of adaptive amino acid evolution. Further analyses indicate that of the seven amino acid fixations that occurred in the D. mojavensis lineage, two of them occur in the active site pocket, potentially having a significant effect on substrate specificity and in the adaptation to alternative cactus hosts.
Population Genetic Analysis of the N-Acylsphingosine Amidohydrolase Gene Associated With Mental Activity in Humans
Authors: Kim Hie Lim , Satta Yoko 
Published: February 2008

Abstract
To understand the evolution of human mental activity, we performed population genetic analyses of nucleotide sequences (∼11 kb) from a worldwide sample of 60 chromosomes of the N-acylsphingosine amidohydrolase (ASAH1) gene. ASAH1 hydrolyzes ceramides and regulates neuronal development, and its deficiency often results in mental retardation. In the region (∼4.4 kb) encompassing exons 3 and 4 of this gene, two distinct lineages (V and M) have been segregating in the human population for 2.4 ± 0.4 million years (MY). The persistence of these two lineages is attributed to ancient population structure of humans in Africa. However, all haplotypes belonging to the V lineage exhibit strong linkage disequilibrium, a high frequency (62%), and small nucleotide diversity (π = 0.05%). These features indicate a signature of positive Darwinian selection for the V lineage. Compared with the orthologs in mammals and birds, it is only Val at amino acid site 72 that is found exclusively in the V lineage in humans, suggesting that this Val is a likely target of positive selection. Computer simulation confirms that demographic models of modern humans except for the ancient population structure cannot explain the presence of two distinct lineages, and neutrality is incompatible with the observed small genetic variation of the V lineage at ASAH1. On the basis of the above observations, it is argued that positive selection is possibly operating on ASAH1 in the modern human population.
DAF-16-Dependent Suppression of Immunity During Reproduction inCaenorhabditis elegans
Authors: Miyata Sachiko , Begun Jakob , Troemel Emily R , Ausubel Frederick M 
Published: February 2008

AbstractTo further understand how the nematode Caenorhabditis elegans defends itself against pathogen attack, we analyzed enhanced pathogen resistance (epr) mutants obtained from a forward genetic screen. We also examined several well-characterized sterile mutants that exhibit an Epr phenotype. We found that sterility and pathogen resistance are highly correlated and that resistance in both epr and sterile mutants is dependent on DAF-16 activity. Our data indicate that a DAF-16-dependent signaling pathway distinct from previously described pathways is involved in the activation of genes that confer resistance to bacterial pathogens. The timing of DAF-16-dependent gene activation in sterile mutants coincides with the onset of embryonic development in wild-type animals, suggesting that signals from developing embryos normally downregulate the immune response.
Essay Contest Reveals Misconceptions of High School Students in Genetics Content
Authors: Mills Shaw Kenna R , Van Horne Katie , Zhang Hubert , Boughman Joann 
Published: February 2008

Abstract
National educational organizations have called upon scientists to become involved in K–12 education reform. From sporadic interaction with students to more sustained partnerships with teachers, the engagement of scientists takes many forms. In this case, scientists from the American Society of Human Genetics (ASHG), the Genetics Society of America (GSA), and the National Society of Genetic Counselors (NSGC) have partnered to organize an essay contest for high school students as part of the activities surrounding National DNA Day. We describe a systematic analysis of 500 of 2443 total essays submitted in response to this contest over 2 years. Our analysis reveals the nature of student misconceptions in genetics, the possible sources of these misconceptions, and potential ways to galvanize genetics education.
Mutations in the Drosophila Mitochondrial tRNA Amidotransferase, bene/gatA, Cause Growth Defects in Mitotic and Endoreplicating Tissues
Authors: Morris Jason Z , Bergman Leah , Kruyer Anna , Gertsberg Mikhail , Guigova Adriana , Arias Ronald , Pogorzelska Monika 
Published: February 2008

Abstract
Rapid larval growth is essential in the development of most metazoans. In this article, we show that bene, a gene previously identified on the basis of its oogenesis defects, is also required for larval growth and viability. We show that all bene alleles disrupt gatA, which encodes the Drosophila homolog of glutamyl-tRNA(Gln) amidotransferase subunit A (GatA). bene alleles are now referred to as gatA. GatA proteins are highly conserved throughout eukaryotes and many prokaryotes. These enzymes are required for proper translation of the proteins encoded by the mitochondrial genome and by many eubacterial genomes. Mitotic and endoreplicating tissues in Drosophila gatA loss-of-function mutants grow slowly and never achieve wild-type size, and gatA larvae die before pupariation. gatA mutant eye clones exhibit growth and differentiation defects, indicating that gatA expression is required cell autonomously for normal growth. The gatA gene is widely expressed in mitotic and endoreplicating tissues.
Implementing a Community-Based Falls-Prevention Program: From Drawing Board to Reality
Authors: Filiatrault Johanne , Parisien Manon , Laforest Sophie , Genest Carole , Gauvin Lise , Fournier Michel , Trickey Francine , Robitaille Yvonne 
Published: February 2008

ABSTRACTSeveral studies have demonstrated the efficacy of falls-prevention programs designed for community-dwelling seniors using randomized designs. However, little is known about the feasibility of implementing these programs under natural conditions and about the success of these programs when delivered under such conditions. The objectives of this paper are to (a) describe a multifactorial falls-prevention program (called Stand Up!) designed for independent community-dwelling seniors and (b) present the results of an analysis of the practicability of implementing this program in community-based settings. The program was implemented in the context of an effectiveness study in 10 community-based organizations in the Montreal metropolitan area. Data pertaining to the reach and delivery of the program as well as participation level show that a falls-prevention program addressing multiple risk factors can be successfully implemented in community-based settings.
Seniors Falls Investigative Methodology (SFIM): A Systems Approach to the Study of Falls in Seniors
Authors: Zecevic Aleksandra A. , Salmoni Alan W. , Lewko John H. , Vandervoort Anthony A. 
Published: February 2008

ABSTRACTAn in-depth understanding of human factors and human error is lacking in current research on seniors' falls. Additional knowledge is needed to understand why seniors are falling. The purpose of this article is to describe the adapting of the Integrated Safety Investigation Methodology (ISIM) (used for investigating transportation and industrial accidents) to studying seniors' falls. An adapted version—the Seniors Falls Investigative Methodology (SFIM)—uses a systems approach to take an investigation beyond the immediate cause of an incident and reveal unsafe acts and deeply imbedded unsafe conditions that contribute to adverse outcomes. An example case study is used to describe six phases of the investigative process in detail. The SFIM has the potential to identify safety deficiencies; utilize existing knowledge about falls; establish a standardized reporting system; shift focus from the faller to the system; and guide targeted prevention.
A novel locus for idiopathic generalized epilepsy in French‐Canadian families maps to 10p11
Authors: Kinirons Peter , Verlaan Dominique J. , Dubé Marie‐Pierre , Poirier Josée , Deacon Charles , Lortie Anne , Clément Jean‐François , Desbiens Richard , Carmant Lionel , Cieuta‐Walti Cecile , Shevell Michael , Rouleau Guy A. , Cossette Patrick 
Published: February 2008

AbstractIdiopathic generalized epilepsy (IGE) has evidence of a strong genetic etiology. We conducted genomewide linkage analysis for genes responsible for familial IGE in French‐Canadian pedigrees. Twenty families segregating autosomal dominant epilepsy were collected. Four larger IGE families sufficiently powerful for independent linkage analysis were genome‐scanned and follow‐up fine mapping was performed over regions with LOD scores >3.0. The genotyping of 16 smaller families was carried out at significantly linked loci for supportive linkage analysis and haplotype comparisons. One of the four families provided a significant linkage result at marker D10S1426 on chromosome 10 (two‐point LOD score = 3.05, theta = 0, multipoint LOD score = 3.18). Fine mapping revealed a segregating haplotype and key recombination breakpoints, suggesting a candidate gene interval of 6.5 Mb. Multipoint linkage analyses using the additional 16 families yielded a maximum LOD score under heterogeneity of 4.23 (alpha = 0.34) at this locus. Evaluation of recombination breakpoints in these families narrowed the candidate region to 1.7 Mb. Sequencing of the two known genes in this region, NRP1 and PARD3, was negative for mutation. Replication of linkage to this locus in other cohorts of IGE families is essential to characterize the underlying genetic mechanism for the disease. © 2008 Wiley‐Liss, Inc.
Prenatal diagnosis of mosaic trisomy 8q studied by ultrasound, cytogenetics, and array‐CGH
Authors: Wood Elizabeth , Dowey Sarah , Saul Daniel , Cain Colyn , Rossiter Judith , Blakemore Karin , Stetten Gail 
Published: February 2008

AbstractMosaic trisomy 8, also known as Warkany syndrome, has a well‐characterized constellation of phenotypic findings. Partial trisomy 8, including mosaic cases, has also been reported, with outcome and counseling dependent on the chromosomal segment involved and whether accompanied by partial aneuploidy for other chromosomes. We present a case of a fetus mosaic for trisomy of the entire long arm (q) of chromosome 8 without additional chromosomal aberrations. The diagnosis was made by amniocentesis performed following an 18 week sonogram that showed multiple fetal anomalies. Mosaicism for trisomy 8q was confirmed by routine karyotyping and fluorescent in situ hybridization (FISH) analysis. The case proved useful for testing the sensitivity of array comparative genomic hybridization (array‐CGH) with respect to segmental trisomy in the presence of chromosomal mosaicism. The phenotype of this fetus, which appears to be the first reported case involving mosaic trisomy 8 for the entire q arm of the chromosome, is described and compared to previously reported cases involving partial trisomy 8q. © 2008 Wiley‐Liss, Inc.
X‐linked congenital ataxia: A new locus maps to Xq25‐q27.1
Authors: Zanni Ginevra , Bertini Enrico , Bellcross Cecelia , Nedelec Brigitte , Froyen Guy , Neuhäuser Gerhard , Opitz John M. , Chelly Jamel 
Published: February 2008

AbstractWe report clinical and molecular studies on a large American family of Norwegian descent with X‐linked nonprogressive congenital ataxia (XCA) in six affected males over three generations. Neuroimaging showed global cerebellar hypoplasia without evidence of supratentorial anomalies. Linkage analysis resulted in a maximum LOD score Z = 3.44 for marker DXS1192 at θ = 0.0 with flanking markers DXS1047 and DXS1227 defining a region of 12 cM in Xq25‐q27.1. The clinical and neuroradiological findings in the present family are very similar to those described in two reported X‐linked families [Illarioshkin et al., 1996; Bertini et al., 2000]; however, the newly identified locus does not overlap with the one defined previously, indicating that there are at least two genes responsible for this rare form of X‐linked congenital cerebellar ataxia with normal intelligence. © 2008 Wiley‐Liss, Inc.
3q29 interstitial microduplication: A new syndrome in a three‐generation family
Authors: Lisi Emily C. , Hamosh Ada , Doheny Kimberly F. , Squibb Elizabeth , Jackson Barbara , Galczynski Rebecca , Thomas George H. , Batista Denise A.S. 
Published: February 2008

AbstractMicrodeletion and microduplication genetic syndromes are known to be a significant cause of developmental delay and dysmorphology. Utilizing high‐resolution chromosome analysis, array CGH and SNP technologies we identified a novel genomic syndrome comprising of an interstitial duplication of approximately 1.61 Mb at the distal end of chromosome 3 band q29. The imbalance was present in five individuals in a three generation family with clinical features including mild to moderate mental retardation and microcephaly. The duplicated segment overlaps with and is the genomic counterpart of the recently described microdeletion of 3q29. Both syndromes are proposed to occur by non‐allelic homologous recombination between regions of low copy repeats present around the breakpoints. © 2008 Wiley‐Liss, Inc.
Novel mutations causing medium chain acyl‐CoA dehydrogenase deficiency: Under‐representation of the common c.985 A > G mutation in the New York state population
Authors: Nichols Matthew J. , Saavedra‐Matiz Carlos A. , Pass Kenneth A. , Caggana Michele 
Published: February 2008

AbstractMedium chain acyl‐CoA dehydrogenase deficiency (MCADD) is one of the most common fatty acid oxidation disorders. A subpopulation of children with MCADD present with metabolic crisis induced by fasting or illness, become lethargic, and can experience seizures or coma, culminating in a 20% mortality rate during the first episode. The frequency of these metabolic crises can be reduced with early diagnosis and treatment. The prevalence of MCADD in the United States is estimated to be 1 per 15,000 with p.K304E (c.985A > G) accounting for 90% of mutant alleles. In an 18‐month period after initiating screening, the New York State Newborn Screening Mass Spectrometry Laboratory screened 385,893 newborns and referred 511 samples with elevated (≥0.3 µmol/L) octanoylcarnitine (C8) levels for molecular testing. Of these referrals, six p.K304E homozygotes and 154 heterozygotes were identified. Twenty infants were biochemically confirmed with MCADD, per report from the child's pediatrician and/or treatment center. In these 20 cases, p.K304E accounted for only 47.5% of the mutant alleles. Further testing showed a second variant, p.Y42H, accounted for 7.5% of mutant alleles while the remaining 45% were unknown. Samples from all diagnosed non‐p.K304E homozygous infants, and samples with C8 levels ≥1.0 µmol/L were sequenced (n = 16). Six novel and seven previously reported mutations were detected. These results suggest that p.K304E has a far lower representation in New York newborns with MCADD than current literature estimates and its full mutational spectrum is still unknown. © 2008 Wiley‐Liss, Inc.
Ramos‐Arroyo syndrome: Long‐term follow‐up of previously reported family
Authors: Spurrier Jamie L. , Weaver David D. 
Published: February 2008

AbstractHere we report on a family with corneal anesthesia, absence of the peripapillary choriocapillaris and retinal pigment epithelium, bilateral sensorineural hearing loss, unusual facial appearance, persistent ductus arteriosus, Hirschsprung disease, and moderate mental retardation. The first two generations of this family were reported previously by Ramos‐Arroyo et al. [Ramos‐Arroyo et al., 1987]. Two further affected individuals have been born into this family and we have observed additional manifestations not previously reported that appear to be part of this syndrome. The differential diagnosis of the condition is also discussed. We think this is a distinct autosomal dominant syndrome with variable expressivity, and have named the disorder the Ramos‐Arroyo syndrome. © 2008 Wiley‐Liss, Inc.
Genetic analysis of chromosome 11p13 and the PAX6 gene in a series of 125 cases referred with aniridia
Authors: Robinson David O. , Howarth Rachel J. , Williamson Kathleen A. , van Heyningen Veronica , Beal Sarah J. , Crolla John A. 
Published: February 2008

AbstractA series of 125 patients referred primarily with aniridia classified as either sporadic (74), familial (24), or in association with WAGR syndrome (14) or other malformations (13) was analysed for mutations, initially by karyotyping and targeted FISH analysis of chromosome 11p13. These methods identified mutations in a significant proportion of patients, 34/125 (27%). Two cases had chromosome rearrangements involving 11p13, 16 cases had visible deletions, and 16 cases had cryptic deletions identified by FISH. The frequency of cryptic deletions in familial aniridia was 27% and in sporadic isolated aniridia was 22%. Of the 14 cases referred with WAGR syndrome, 10 (71%) had chromosomal deletions, 2 cryptic and 8 visible. Of the 13 cases with aniridia and other malformations, 5 (38%) had a chromosomal rearrangement or deletion. In 37 cases with no karyotypic or cryptic chromosome abnormality, sequence analysis of the PAX6 gene was performed. Mutations were identified in 33 cases; 22 with sporadic aniridia, 10 with familial aniridia and 1 with aniridia and other non‐WAGR syndrome associated anomalies. Overall, 67 of 71 cases (94%) undergoing full mutation analysis had a mutation in the PAX6 genomic region. © 2008 Wiley‐Liss, Inc.