bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phenotypic Variation Resulting From a Deficiency of Epidermal Growth Factor Receptor in Mice Is Caused by Extensive Genetic Heterogeneity That Can Be Genetically and Molecularly Partitioned
Authors: Strunk Karen E , Amann Vicky , Threadgill David W 
Published: September 2004

Abstract
The timing of lethality caused by homozygosity for a null allele of the epidermal growth factor receptor (Egfrtm1Mag) in mice is strongly dependent on genetic background. Initial attempts to genetically map background modifiers using Swiss-derived, outbred CD-1 mice were unsuccessful. To investigate the genetic architecture contributing to survival of Egfrtm1Mag homozygous embryos, the genetic variability segregating within the outbred population was partitioned by surveying viability of Egfrtm1Mag mutants using intercrosses between 129S6/SvEvTAC-Egfrtm1Mag and nine Swiss-derived, inbred strains: ALR/LtJ, ALS/LtJ, APN, APS, ICR/HaRos, NOD/LtJ, NON/LtJ, SJL/J, and SWR/J. The observations showed that these strains support varying levels of survival of Egfrtm1Mag homozygous embryos, suggesting that genetic heterogeneity within the CD-1 stock contributed to the original lack of Egfrtm1Mag modifier detection. Similar to the Swiss-derived intercrosses, nine congenic strains, derived from 129S6/SvEvTAC, AKR/J, APN, BALB/cJ, BTBR-T+ tf/tf, C3H/HeJ, C57BL/6J, DBA/2J, and FVB/NJ inbred backgrounds, also supported varying levels of survival of Egfrtm1Mag mutants. By intercrossing the congenic lines to create hybrid F1 embryos, different genetic backgrounds were found to have complementary modifiers. Analysis of the congenic lines argues against heterosis of outbred backgrounds contributing to Egfrtm1Mag phenotypic variability. A detailed analysis of the crosses suggests that modifiers function at three distinct stages of development. One class of modifiers supports survival of Egfrtm1Mag homozygous embryos to mid-gestation, another class supports development through the mid-gestation transition from yolk-sac to placental-derived nutrient sources, and a third class supports survival through later stages of gestation. Data from microarray analysis using RNA from wild-type and Egfrtm1Mag mutant placentas support the existence of extensive genetic heterogeneity and suggest that it can be molecularly partitioned. This method should be generally useful to partition heterogeneity contributing to other complex traits.
Conditional Probability Methods for Haplotyping in Pedigrees
Authors: Gao Guimin , Hoeschele Ina , Sorensen Peter , Du Fengxing 
Published: September 2004

Abstract
Efficient haplotyping in pedigrees is important for the fine mapping of quantitative trait locus (QTL) or complex disease genes. To reconstruct haplotypes efficiently for a large pedigree with a large number of linked loci, two algorithms based on conditional probabilities and likelihood computations are presented. The first algorithm (the conditional probability method) produces a single, approximately optimal haplotype configuration, with computing time increasing linearly in the number of linked loci and the pedigree size. The other algorithm (the conditional enumeration method) identifies a set of haplotype configurations with high probabilities conditional on the observed genotype data for a pedigree. Its computing time increases less than exponentially with the size of a subset of the set of person-loci with unordered genotypes and linearly with its complement. The size of the subset is controlled by a threshold parameter. The set of identified haplotype configurations can be used to estimate the identity-by-descent (IBD) matrix at a map position for a pedigree. The algorithms have been tested on published and simulated data sets. The new haplotyping methods are much faster and provide more information than several existing stochastic and rule-based methods. The accuracies of the new methods are equivalent to or better than those of these existing methods.
In Vivo Interaction Between Mitochondria Carrying mtDNAs From Different Mouse Species
Authors: Sato Akitsugu , Nakada Kazuto , Shitara Hiroshi , Yonekawa Hiromichi , Hayashi Jun-Ichi 
Published: September 2004

Abstract
Mitochondrial disease model mice, mitomice, were created using zygotes of B6mtspr strain mice carrying mitochondrial DNA (mtDNA) from Mus spretus as recipients of exogenous mitochondria carrying wild-type and a deletion mutant mtDNA (ΔmtDNA) of M. musculus domesticus. In these experiments, mtDNAs from different mouse species were used for identification of exo- and endogenous wild-type mtDNAs in the mitomice. Results showed transmission of exogenous ΔmtDNA, but not exogenous wild-type mtDNA, of M. m. domesticus to following generations through the female germ line. Complete elimination of exogenous wild-type mtDNA would be due to stochastic segregation, whereas transmission of exogenous ΔmtDNA would be due to its smaller size leading to a propagational advantage. Tissues in mitomice of the F3 generation carrying exogenous ΔmtDNA showed protection from respiration defects until ΔmtDNA accumulated predominantly. This protection from expression of mitochondrial dysfunction was attained with the help of endogenous wild-type mtDNA of M. spretus, since mitomice did not possess exogenous wild-type mtDNA of M. m. domesticus. These observations provide unambiguous evidence for the presence of interaction between exogenous mitochondria carrying ΔmtDNA and endogenous mitochondria carrying M. spretus wild-type mtDNA.
Multiple-Interval Mapping for Quantitative Trait Loci Controlling Endosperm Traits
Authors: Kao Chen-Hung 
Published: September 2004

AbstractEndosperm traits are trisomic inheritant and are of great economic importance because they are usually directly related to grain quality. Mapping for quantitative trait loci (QTL) underlying endosperm traits can provide an efficient way to genetically improve grain quality. As the traditional QTL mapping methods (diploid methods) are usually designed for traits under diploid control, they are not the ideal approaches to map endosperm traits because they ignore the triploid nature of endosperm. In this article, a statistical method considering the triploid nature of endosperm (triploid method) is developed on the basis of multiple-interval mapping (MIM) to map for the underlying QTL. The proposed triploid MIM method is derived to broadly use the marker information either from only the maternal plants or from both the maternal plants and their embryos in the backcross and F2 populations for mapping endosperm traits. Due to the use of multiple intervals simultaneously to take multiple QTL into account, the triploid MIM method can provide better detection power and estimation precision, and as shown in this article it is capable of analyzing and searching for epistatic QTL directly as compared to the traditional diploid methods and current triploid methods using only one (or two) interval(s). Several important issues in endosperm trait mapping, such as the relation and differences between the diploid and triploid methods, variance components of genetic variation, and the problems if effects are present and ignored, are also addressed. Simulations are performed to further explore these issues, to investigate the relative efficiency of different experimental designs, and to evaluate the performance of the proposed and current methods in mapping endosperm traits. The MIM-based triploid method can provide a powerful tool to estimate the genetic architecture of endosperm traits and to assist the marker-assisted selection for the improvement of grain quality in crop science. The triploid MIM FORTRAN program for mapping endosperm traits is available on the worldwide web (http://www.stat.sinica.edu.tw/chkao/).
CDC7/DBF4 Functions in the Translesion Synthesis Branch of the RAD6 Epistasis Group in Saccharomyces cerevisiae
Authors: Pessoa-Brandão Luis , Sclafani Robert A 
Published: September 2004

AbstractCDC7 and DBF4 encode the essential Cdc7-Dbf4 protein kinase required for DNA replication in eukaryotes from yeast to human. Cdc7-Dbf4 is also required for DNA damage-induced mutagenesis, one of several postreplicational DNA damage tolerance mechanisms mediated by the RAD6 epistasis group. Several genes have been determined to function in separate branches within this group, including RAD5, REV3/REV7 (Pol ζ), RAD30 (Pol η), and POL30 (PCNA). An extensive genetic analysis of the interactions between CDC7 and REV3, RAD30, RAD5, or POL30 in response to DNA damage was done to determine its role in the RAD6 pathway. CDC7, RAD5, POL30, and RAD30 were found to constitute four separate branches of the RAD6 epistasis group in response to UV and MMS exposure. CDC7 is also shown to function separately from REV3 in response to MMS. However, they belong in the same pathway in response to UV. We propose that the Cdc7-Dbf4 kinase associates with components of the translesion synthesis pathway and that this interaction is dependent upon the type of DNA damage. Finally, activation of the DNA damage checkpoint and the resulting cell cycle delay is intact in cdc7Δ mcm5-bob1 cells, suggesting a direct role for CDC7 in DNA repair/damage tolerance.
The Genetic Architecture of the Behavioral Ontogeny of Foraging in Honeybee Workers
Authors: Rueppell Olav , Pankiw Tanya , Nielsen David I , Fondrk M Kim , Beye Martin , Page Robert E 
Published: September 2004

Abstract
The initiation of foraging during the life course of honeybee workers is of central interest to understanding the division of labor in social insects, a central theme in sociobiology and behavioral research. It also provides one of the most complex phenotypic traits in biological systems because of the interaction of various external, social, and individual factors. This study reports on a comprehensive investigation of the genetic architecture of the age of foraging initiation in honeybees. It comprises an estimation of genetic variation, the study of candidate loci, and two complementary quantitative trait loci (QTL) maps using two selected, continually bred lines of honeybees. We conclude that considerable genetic variation exists between the selected lines for this central life history component. The study reveals direct pleiotropic and epistatic effects of candidate loci (including previously identified QTL for foraging behavior). Furthermore, two maps of the honeybee genome were constructed from over 400 AFLP markers. Both maps confirm the extraordinary recombinational size of the honeybee genome. On the basis of these maps, we report four new significant QTL and two more suggestive QTL that influence the initiation of foraging.
Evidence for Multiple Alleles at the DGAT1 Locus Better Explains a Quantitative Trait Locus With Major Effect on Milk Fat Content in Cattle
Authors: Kühn Christa , Thaller Georg , Winter Andreas , Bininda-Emonds Olaf R P , Kaupe Bernhard , Erhardt Georg , Bennewitz Jörn , Schwerin Manfred , Fries Ruedi 
Published: September 2004

Abstract
A quantitative trait locus (QTL) for milk fat percentage has been mapped consistently to the centromeric region of bovine chromosome 14 (BTA14). Two independent studies have identified the nonconservative mutation K232A in the acylCoA-diacylglycerol-acyltransferase 1 (DGAT1) gene as likely to be causal for the observed variation. Here we provide evidence for additional genetic variability at the same QTL that is associated with milk fat percentage variation within the German Holstein population. Namely, we show that alleles of the DGAT1 promoter derived from the variable number of tandem repeat (VNTR) polymorphism are associated with milk fat content in animals homozygous for the allele 232A at DGAT1. Our results present another example for more than two trait-associated alleles being involved in a major gene effect on a quantitative trait. The segregation of multiple alleles affecting milk production traits at the QTL on BTA14 has to be considered whenever marker-assisted selection programs are implemented in dairy cattle. Due to the presence of a potential transcription factor binding site in the 18mer element of the VNTR, the variation in the number of tandem repeats of the 18mer element might be causal for the variability in the transcription level of the DGAT1 gene.
Simultaneous Detection of Linkage Disequilibrium and Genetic Differentiation of Subdivided Populations
Authors: Kitada Shuichi , Kishino Hirohisa 
Published: September 2004

Abstract
We propose a new method for simultaneously detecting linkage disequilibrium and genetic structure in subdivided populations. Taking subpopulation structure into account with a hierarchical model, we estimate the magnitude of genetic differentiation and linkage disequilibrium in a metapopulation on the basis of geographical samples, rather than decompose a population into a finite number of random-mating subpopulations. We assume that Hardy-Weinberg equilibrium is satisfied in each locality, but do not assume independence between marker loci. Linkage states remain unknown. Genetic differentiation and linkage disequilibrium are expressed as hyperparameters describing the prior distribution of genotypes or haplotypes. We estimate related parameters by maximizing marginal-likelihood functions and detect linkage equilibrium or disequilibrium by the Akaike information criterion. Our empirical Bayesian model analyzes genotype and haplotype frequencies regardless of haploid or diploid data, so it can be applied to most commonly used genetic markers. The performance of our procedure is examined via numerical simulations in comparison with classical procedures. Finally, we analyze isozyme data of ayu, a severely exploited fish species, and single-nucleotide polymorphisms in human ALDH2.
Estimating the Frequency of Events That Cause Multiple-Nucleotide Changes
Authors: Whelan Simon , Goldman Nick 
Published: September 2004

Abstract
Existing mathematical models of DNA sequence evolution assume that all substitutions derive from point mutations. There is, however, increasing evidence that larger-scale events, involving two or more consecutive sites, may also be important. We describe a model, denoted SDT, that allows for single-nucleotide, doublet, and triplet mutations. Applied to protein-coding DNA, the SDT model allows doublet and triplet mutations to overlap codon boundaries but still permits data to be analyzed using the simplifying assumption of independence of sites. We have implemented the SDT model for maximum-likelihood phylogenetic inference and have applied it to an alignment of mammalian globin sequences and to 258 other protein-coding sequence alignments from the Pandit database. We find the SDT model's inclusion of doublet and triplet mutations to be overwhelmingly successful in giving statistically significant improvements in fit of model to data, indicating that larger-scale mutation events do occur. Distributions of inferred parameter values over all alignments analyzed suggest that these events are far more prevalent than previously thought. Detailed consideration of our results and the absence of any known mechanism causing three adjacent nucleotides to be substituted simultaneously, however, leads us to suggest that the actual evolutionary events occurring may include still-larger-scale events, such as gene conversion, inversion, or recombination, or a series of rapid compensatory changes.
Pervasive Genomic Recombination of HIV-1 in VivoSequence data from this article have been deposited with the EMBL/GenBank Data Libraries under accession nos. AY496645, AY496646, AY496647, AY496648, AY496649, AY496650, AY496651, AY496652, AY496653, AY496654, AY496655, AY496656, AY496657, AY496658, AY496659, AY496660, AY496661, AY496662, AY496663, AY496664, AY496665, AY496666, AY496667, AY496668, AY496669, AY496670, AY496671, AY496672, AY496673, AY496674, AY496675, AY496676, AY496677, AY496678, AY496679, AY496680, AY496681, AY496682, AY496683, AY496684.
Authors: Shriner Daniel , Rodrigo Allen G , Nickle David C , Mullins James I 
Published: September 2004

Abstract
Recombinants of preexisting human immunodeficiency virus type 1 (HIV-1) strains are now circulating globally. To increase our understanding of the importance of these recombinants, we assessed recombination within an individual infected from a single source by studying the linkage patterns of the auxiliary genes of HIV-1 subtype B. Maximum-likelihood phylogenetic techniques revealed evidence for recombination from topological incongruence among adjacent genes. Coalescent methods were then used to estimate the in vivo recombination rate. The estimated mean rate of 1.38 × 10−4 recombination events/adjacent sites/generation is ∼5.5-fold greater than the reported point mutation rate of 2.5 × 10−5/site/generation. Recombination was found to be frequent enough to mask evidence for purifying selection by Tajima's D test. Thus, recombination is a major evolutionary force affecting genetic variation within an HIV-1-infected individual, of the same order of magnitude as point mutational change.
The Role of cis-acting Sequences Governing Catabolite Repression Control of lacS Expression in the Archaeon Sulfolobus solfataricus
Authors: Hoang Viet , Bini Elisabetta , Dixit Vidula , Drozda Melissa , Blum Paul 
Published: September 2004

Abstract
The archaeon Sulfolobus solfataricus uses a catabolite repression-like system to control production of several glycoside hydrolases. To better understand this regulatory system, studies of the regulation of expression of the β-glycosidase gene (lacS) were conducted. Expression of lacS varies in response to medium composition and to mutations at an unlinked gene called car. Despite gene overlap, expression of the lacS promoter proximal gene, SSO3017, exhibited coregulation but not cotranscription with lacS. Measurements of mRNA half-life excluded differential stability as a factor in lacS regulation. Chromosomal repositioning by homologous recombination of a lacS deletion series clarified critical cis-acting sequences required for lacS regulation. lacS repositioned at amyA exhibited increased lacS expression and compromised the response to medium composition independently of lacS 5′ flanking sequence composition. In contrast, regulation of lacS by the car mutation was dependent on sequences upstream of the archaeal TATA box. Expression of a promoter fusion between lacS and the car-independent malA promoter integrated either at amyA or at the natural lacS locus was insensitive to the allelic state of car. In contrast, the promoter fusion retained a response to medium composition only at the lacS locus. These results indicate that car acts at the lacS promoter and that the response to medium composition involves locus-specific sequences exclusive of those present 5′ to lacS or within the lacS transcription unit.
Genes Encoding Subunits of Stable Complexes Are Clustered on the Yeast Chromosomes
Authors: Teichmann Sarah Amalia , Veitia Reiner Albert 
Published: September 2004

AbstractGenomic evidence for colocalization of functionally related genes on eukaryote chromosomes is mounting. Here we show that a statistically significant fraction of yeast genes coding for subunits of stable complexes are located within 10–30 kb of each other. Clustering of genes encoding subunits of complexes may ensure better coregulation and maintain the right stoichiometry of complexes upon duplication of chromosomal segments.
A Network of Stimulatory and Inhibitory Gα-Subunits Regulates Olfaction in Caenorhabditis elegans
Authors: Lans Hannes , Rademakers Suzanne , Jansen Gert 
Published: September 2004

Abstract
The two pairs of sensory neurons of C. elegans, AWA and AWC, that mediate odorant attraction, express six Gα-subunits, suggesting that olfaction is regulated by a complex signaling network. Here, we describe the cellular localization and functions of the six olfactory Gα-subunits: GPA-2, GPA-3, GPA-5, GPA-6, GPA-13, and ODR-3. All except GPA-6 localize to sensory cilia, suggesting a direct role in sensory transduction. GPA-2, GPA-3, GPA-5, and GPA-6 are also present in cell bodies and axons and GPA-5 specifically localizes to synaptic sites. Analysis of animals with single- to sixfold loss-of-function mutations shows that olfaction involves a balance between multiple stimulatory and inhibitory signals. ODR-3 constitutes the main stimulatory signal and is sufficient for the detection of odorants. GPA-3 forms a second stimulatory signal in the AWA and AWC neurons, also sufficient for odorant detection. In AWA, signaling is suppressed by GPA-5. In AWC, GPA-2 and GPA-13 negatively and positively regulate signaling, respectively. Finally, we show that only ODR-3 plays a role in cilia morphogenesis. Defects in this process are, however, independent of olfactory behavior. Our findings reveal the existence of a complex signaling network that controls odorant detection by C. elegans.
A Fast Algorithm for Functional Mapping of Complex Traits
Authors: Zhao Wei , Wu Rongling , Ma Chang-Xing , Casella George 
Published: September 2004

AbstractBy integrating the underlying developmental mechanisms for the phenotypic formation of traits into a mapping framework, functional mapping has emerged as an important statistical approach for mapping complex traits. In this note, we explore the feasibility of using the simplex algorithm as an alternative to solve the mixture-based likelihood for functional mapping of complex traits. The results from the simplex algorithm are consistent with those from the traditional EM algorithm, but the simplex algorithm has considerably reduced computational times. Moreover, because of its nonderivative nature and easy implementation with current software, the simplex algorithm enjoys an advantage over the EM algorithm in the dynamic modeling and analysis of complex traits.
Evolution of Specialists in an Experimental Microcosm
Authors: Dykhuizen Daniel E , Dean Antony M 
Published: September 2004

Abstract
The impact of adaptation on the persistence of a balanced polymorphism was explored using the lactose operon of Escherichia coli as a model system. Competition in chemostats for two substitutable resources, methylgalactoside and lactulose, generates stabilizing frequency-dependent selection when two different naturally isolated lac operons (TD2 and TD10) are used. The fate of this balanced polymorphism was tracked over evolutionary time by monitoring the frequency of fhuA−, a linked neutral genetic marker that confers resistance to the bacteriophage T5. In four out of nine chemostats the lac polymorphism persisted for 400–600 generations when the experiments were terminated. In the other five chemostats the fhuA polymorphism, and consequently the lac operon polymorphism, was lost between 86 and 219 generations. Four of 13 chemostat cultures monomorphic for the lac operon retained the neutral fhuA polymorphism for 450–550 generations until they were terminated; the remainder became monomorphic at fhuA between 63 and 303 generations. Specialists on each galactoside were isolated from chemostats that maintained the fhuA polymorphism, whether polymorphic or monomorphic at the lac operon. Strains isolated from three of four chemostats in which the lac polymorphism was preserved had switched their galactoside preference. Most of the chemostats where the fhuA polymorphism was lost also contained specialists. These results demonstrate that the initial polymorphism at lac was of little consequence to the outcome of long-term adaptive evolution. Instead, the fitnesses of evolved strains were dominated by mutations arising elsewhere in the genome, a fact confirmed by showing that operons isolated from their evolved backgrounds were alone unable to explain the presence of both specialists. Our results suggest that, once stabilized, ecological specialization prevented selective sweeps through the entire population, thereby promoting the maintenance of linked neutral polymorphisms.