bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic Effective Size Is Three Orders of Magnitude Smaller Than Adult Census Size in an Abundant, Estuarine-Dependent Marine Fish (Sciaenops ocellatus)
Authors: Turner Thomas F , Wares John P , Gold John R 
Published: April 2021

Abstract
Using eight microsatellite loci and a variety of analytical methods, we estimated genetic effective size (Ne) of an abundant and long-lived marine fish species, the red drum (Sciaenops ocellatus), in the northern Gulf of Mexico (Gulf). The ratio Ne/N, where short-term variance Ne was estimated via the temporal method from shifts in allele-frequency data over four cohorts and where N reflected a current estimate of adult census size in the northern Gulf, was ∼0.001. In an idealized population, this ratio should approximate unity. The extraordinarily low value of Ne/N appears to arise from high variance in individual reproductive success and perhaps more importantly from variance in productivity of critical spawning and nursery habitats located in spatially discrete bays and estuaries throughout the northern Gulf. An estimate of Ne based on a coalescent approach, which measures long-term, inbreeding effective size, was four orders of magnitude lower than the estimate of current census size, suggesting that factors presently driving Ne/N to low values among red drum in the northern Gulf may have operated similarly in the past. Models that predict Ne/N exclusively from demographic and life-history features will seriously overestimate Ne if variance in reproductive success and variance in productivity among spatially discrete demes is underestimated. Our results indicate that these variances, especially variance in productivity among demes, must be large for red drum. Moreover, our study indicates that vertebrate populations with enormous adult census numbers may still be at risk relative to decline and extinction from genetic factors.
Suppression of the ELO-2 FA Elongation Activity Results in Alterations of the Fatty Acid Composition and Multiple Physiological Defects, Including Abnormal Ultradian Rhythms, in Caenorhabditis elegans
Authors: Kniazeva Marina , Sieber Matt , McCauley Scott , Zhang Kang , Watts Jennifer L , Han Min 
Published: April 2021

Abstract
While the general steps of fatty acid (FA) biosynthesis are well understood, the individual enzymes involved in the elongation of long chain saturated and polyunsaturated FA (PUFA) are largely unknown. Recent research indicates that these enzymes might be of considerable physiological importance for human health. We use Caenorhabditis elegans to study FA elongation activities and associated abnormal phenotypes. In this article we report that the predicted C. elegans F11E6.5/ELO-2 is a functional enzyme with the FA elongation activity. It is responsible for the elongation of palmitic acid and is involved in PUFA biosynthesis. RNAi-mediated suppression of ELO-2 causes an accumulation of palmitate and an associated decrease in the PUFA fraction in triacylglycerides and phospholipid classes. This imbalance in the FA composition results in multiple phenotypic defects such as slow growth, small body size, reproductive defects, and changes in rhythmic behavior. ELO-2 cooperates with the previously reported ELO-1 in 20-carbon PUFA production, and at least one of the enzymes must function to provide normal growth and development in C. elegans. The presented data indicate that suppression of a single enzyme of the FA elongation machinery is enough to affect various organs and systems in worms. This effect resembles syndromic disorders in humans.
Analysis of Ras-Induced Overproliferation in Drosophila Hemocytes
Authors: Asha H , Nagy Istvan , Kovacs Gabor , Stetson Daniel , Ando Istvan , Dearolf Charles R 
Published: April 2021

Abstract
We use the Drosophila melanogaster larval hematopoietic system as an in vivo model for the genetic and functional genomic analysis of oncogenic cell overproliferation. Ras regulates cell proliferation and differentiation in multicellular eukaryotes. To further elucidate the role of activated Ras in cell overproliferation, we generated a collagen promoter-Gal4 strain to overexpress RasV12 in Drosophila hemocytes. Activated Ras causes a dramatic increase in the number of circulating larval hemocytes (blood cells), which is caused by cellular overproliferation. This phenotype is mediated by the Raf/MAPK pathway. The mutant hemocytes retain the ability to phagocytose bacteria as well as to differentiate into lamellocytes. Microarray analysis of hemocytes overexpressing RasV12 vs. Ras+ identified 279 transcripts that are differentially expressed threefold or more in hemocytes expressing activated Ras. This work demonstrates that it will be feasible to combine genetic and functional genomic approaches in the Drosophila hematopoietic system to systematically identify oncogene-specific downstream targets.
Common Spontaneous Sex-Reversed XX males of the Medaka Oryzias latipes
Authors: Nanda Indrajit , Hornung Ute , Kondo Mariko , Schmid Michael , Schartl Manfred 
Published: April 2021

Abstract
In the medaka, a duplicated version of the dmrt1 gene, dmrt1bY, has been identified as a candidate for the master male sex-determining gene on the Y chromosome. By screening several strains of Northern and Southern medaka we identified a considerable number of males with normal phenotype and uncompromised fertility, but lacking dmrt1bY. The frequency of such males was &gt;10% in some strains and zero in others. Analysis for the presence of other Y-linked markers by FISH analysis, PCR, and phenotype indicated that their genotype is XX. Crossing such males with XX females led to a strong female bias in the offspring and also to a reappearance of XX males in the following generations. This indicated that the candidate male sex-determining gene dmrt1bY may not be necessary for male development in every case, but that its function can be taken over by so far unidentified autosomal modifiers.
Molecular Dissection of a Quantitative Trait Locus: A Phenylalanine-to-Tyrosine Substitution in the Transmembrane Domain of the Bovine Growth Hormone Receptor Is Associated With a Major Effect on Milk Yield and Composition
Authors: Blott Sarah , Kim Jong-Joo , Moisio Sirja , Schmidt-Küntzel Anne , Cornet Anne , Berzi Paulette , Cambisano Nadine , Ford Christine , Grisart Bernard , Johnson Dave , Karim Latifa , Simon Patricia , Snell Russell , Spelman Richard , Wong Jerry , Vilkki Johanna , Georges Michel , Farnir Frédéric , Coppieters Wouter 
Published: April 2021

Abstract
We herein report on our efforts to improve the mapping resolution of a QTL with major effect on milk yield and composition that was previously mapped to bovine chromosome 20. By using a denser chromosome 20 marker map and by exploiting linkage disequilibrium using two distinct approaches, we provide strong evidence that a chromosome segment including the gene coding for the growth hormone receptor accounts for at least part of the chromosome 20 QTL effect. By sequencing individuals with known QTL genotype, we identify an F to Y substitution in the transmembrane domain of the growth hormone receptor gene that is associated with a strong effect on milk yield and composition in the general population.
The Role of 2nGametes and Endosperm Balance Number in the Origin and Evolution of Polyploids in the Tuber-Bearing Solanums
Authors: Carputo Domenico , Frusciante Luigi , Peloquin Stanley J 
Published: April 2021

AbstractPolyploidization has played a major role in the origin and evolution of polyploid species. In this article we outline the unique characteristics of 2n gametes and implications of their participation in the evolution of polyploid Solanum species. The genetic consequences of 2n gametes indicate that sexual polyploidization results in greater variability, fitness, and heterozygosity than does somatic doubling. Further, the mechanisms of 2n gamete formation and the frequency of 2n gamete-forming genes in present polyploids and their ancestral species provide additional evidence of their involvement. Equally important is the endosperm, via the endosperm balance number (EBN) incompatibility system, in complementing the role of 2n gametes. In fact, the EBN system acts as a screen for either 1n or 2n gametes, depending on the EBN and chromosome numbers of parental species. EBN in combination with 2n gametes maintains the ploidy integrity of diploid ancestral species, while providing the flexibility for either unilateral or bilateral sexual polyploidization.
Cloning of the Pleiotropic T Locus in Soybean and Two Recessive Alleles That Differentially Affect Structure and Expression of the Encoded Flavonoid 3′ Hydroxylase
Authors: Zabala Gracia , Vodkin Lila 
Published: April 2021

Abstract
Three loci (I, R, and T) control pigmentation of the seed coats in Glycine max and are genetically distinct from those controlling flower color. The T locus also controls color of the trichome hairs. We report the identification and isolation of a flavonoid 3′ hydroxylase gene from G. max (GmF3′H) and the linkage of this gene to the T locus. This GmF3′H gene was highly expressed in early stages of seed coat development and was expressed at very low levels or not at all in other tissues. Evidence that the GmF3′H gene is linked to the T locus came from the occurrence of multiple RFLPs in lines with varying alleles of the T locus, as well as in a population of plants segregating at that locus. GmF3′H genomic and cDNA sequence analysis of color mutant lines with varying t alleles revealed a frameshift mutation in one of the alleles. In another line derived from a mutable genetic stock, the abundance of the mRNAs for GmF3′H was dramatically reduced. Isolation of the GmF3′H gene and its identification as the T locus will enable investigation of the pleiotropic effects of the T locus on cell wall integrity and its involvement in the regulation of the multiple branches of the flavonoid pathway in soybean.
Genetic and Functional Analysis of DD44, a Sex-Linked Gene From the Dioecious Plant Silene latifolia, Provides Clues to Early Events in Sex Chromosome Evolution
Authors: Moore Richard C , Kozyreva Olga , Lebel-Hardenack Sabine , Siroky Jiri , Hobza Roman , Vyskot Boris , Grant Sarah R 
Published: April 2021

Abstract
Silene latifolia is a dioecious plant with heteromorphic sex chromosomes. The sex chromosomes of S. latifolia provide an opportunity to study the early events in sex chromosome evolution because of their relatively recent emergence. In this article, we present the genetic and physical mapping, expression analysis, and molecular evolutionary analysis of a sex-linked gene from S. latifolia, DD44 (Differential Display 44). DD44 is homologous to the oligomycin sensitivity-conferring protein, an essential component of the mitochondrial ATP synthase, and is ubiquitously expressed in both sexes. We have been able to genetically map DD44 to a region of the Y chromosome that is genetically linked to the carpel-suppressing locus. Although we have physically mapped DD44 to the distal end of the long arm of the X chromosome using fluorescence in situ hybridization (FISH), DD44 maps to the opposite arm of the Y chromosome as determined by our genetic map. These data suggest that chromosomal rearrangements have occurred on the Y chromosome, which may have contributed to the genetic isolation of the Y chromosome. We discuss the implications of these results with respect to the structural and functional evolution of the S. latifolia Y chromosome.
Multitrait Fine Mapping of Quantitative Trait Loci Using Combined Linkage Disequilibria and Linkage Analysis
Authors: Lund M S , Sørensen P , Guldbrandtsen B , Sorensen D A 
Published: April 2021

Abstract
A novel multitrait fine-mapping method is presented. The method is implemented by a model that treats QTL effects as random variables. The covariance matrix of allelic effects is proportional to the IBD matrix, where each element is the probability that a pair of alleles is identical by descent, given marker information and QTL position. These probabilities are calculated on the basis of similarities of marker haplotypes of individuals of the first generation of genotyped individuals, using “gene dropping” (linkage disequilibrium) and transmission of markers from genotyped parents to genotyped offspring (linkage). A small simulation study based on a granddaughter design was carried out to illustrate that the method provides accurate estimates of QTL position. Results from the simulation also indicate that it is possible to distinguish between a model postulating one pleiotropic QTL affecting two traits vs. one postulating two closely linked loci, each affecting one of the traits.
Estimating Effective Population Size and Migration Rates From Genetic Samples Over Space and Time
Authors: Wang Jinliang , Whitlock Michael C 
Published: April 2021

AbstractIn the past, moment and likelihood methods have been developed to estimate the effective population size (Ne) on the basis of the observed changes of marker allele frequencies over time, and these have been applied to a large variety of species and populations. Such methods invariably make the critical assumption of a single isolated population receiving no immigrants over the study interval. For most populations in the real world, however, migration is not negligible and can substantially bias estimates of Ne if it is not accounted for. Here we extend previous moment and maximum-likelihood methods to allow the joint estimation of Ne and migration rate (m) using genetic samples over space and time. It is shown that, compared to genetic drift acting alone, migration results in changes in allele frequency that are greater in the short term and smaller in the long term, leading to under- and overestimation of Ne, respectively, if it is ignored. Extensive simulations are run to evaluate the newly developed moment and likelihood methods, which yield generally satisfactory estimates of both Ne and m for populations with widely different effective sizes and migration rates and patterns, given a reasonably large sample size and number of markers.
Saccharomyces cerevisiae Hsp70 Mutations Affect [PSI+] Prion Propagation and Cell Growth Differently and Implicate Hsp40 and Tetratricopeptide Repeat Cochaperones in Impairment of [PSI+]
Authors: Jones Gary W , Masison Daniel C 
Published: April 2021

Abstract
We previously described an Hsp70 mutant (Ssa1-21p), altered in a conserved residue (L483W), that dominantly impairs yeast [PSI+] prion propagation without affecting growth. We generated new SSA1 mutations that impaired [PSI+] propagation and second-site mutations in SSA1-21 that restored normal propagation. Effects of mutations on growth did not correlate with [PSI+] phenotype, revealing differences in Hsp70 function required for growth and [PSI+] propagation and suggesting that Hsp70 interacts differently with [PSI+] prion aggregates than with other cellular substrates. Complementary suppression of altered activity between forward and suppressing mutations suggests that mutations that impair [PSI+] affect a similar Hsp70 function and that suppressing mutations similarly overcome this effect. All new mutations that impaired [PSI+] propagation were located in the ATPase domain. Locations and homology of several suppressing substitutions suggest that they weaken Hsp70's substrate-trapping conformation, implying that impairment of [PSI+] by forward mutations is due to altered ability of the ATPase domain to regulate substrate binding. Other suppressing mutations are in residues important for interactions with Hsp40 or TPR-containing cochaperones, suggesting that such interactions are necessary for the impairment of [PSI+] propagation caused by mutant Ssa1p.
Genetic Loci Modulating Fitness and Life Span in Caenorhabditis elegans: Categorical Trait Interval Mapping in CL2a × Bergerac-BO Recombinant-Inbred Worms
Authors: Ayyadevara Srinivas , Ayyadevara Rajani , Vertino Anthony , Galecki Andrzej , Thaden John J , Reis Robert J Shmookler 
Published: April 2021

Abstract
Quantitative trait loci (QTL) can implicate an unbiased sampling of genes underlying a complex, polygenic phenotype. QTL affecting longevity in Caenorhabditis elegans were mapped using a CL2a × Bergerac-BO recombinant-inbred population. Genotypes were compared at 30 transposon-specific markers for two paired sample sets totaling 171 young controls and 172 longevity-selected worms (the last-surviving 1%) from a synchronously aged population. A third sample set, totaling 161 worms from an independent culture, was analyzed for confirmation of loci. At least six highly significant QTL affecting life span were detected both by single-marker (χ2) analysis and by two interval-mapping procedures—one intended for nonparametric traits and another developed specifically for mapping of categorical traits. These life-span QTL were located on chromosomes I (near the hP4 locus), III (near stP127), IV (near stP44), V (a cluster of three peaks, near stP192, stP23, and stP6), and X (two distinct peaks, near stP129 and stP2). Epistatic effects on longevity were also analyzed by Fisher's exact test, which indicated a significant life-span interaction between markers on chromosomes V (stP128) and III (stP127). Several further interactions were significant in the initial unselected population; two of these, between distal loci on chromosome V, were completely eliminated in the long-lived subset. Allelic longevity effects for two QTL, on chromosomes IV and V, were confirmed in backcrossed congenic lines and were highly significant in two very different environments—growth on solid agar medium and in liquid suspension culture.
Inferring Modes of Colonization for Pest Species Using Heterozygosity Comparisons and a Shared-Allele Test
Authors: Sved J A , Yu H , Dominiak B , Gilchrist A S 
Published: April 2021

AbstractLong-range dispersal of a species may involve either a single long-distance movement from a core population or spreading via unobserved intermediate populations. Where the new populations originate as small propagules, genetic drift may be extreme and gene frequency or assignment methods may not prove useful in determining the relation between the core population and outbreak samples. We describe computationally simple resampling methods for use in this situation to distinguish between the different modes of dispersal. First, estimates of heterozygosity can be used to test for direct sampling from the core population and to estimate the effective size of intermediate populations. Second, a test of sharing of alleles, particularly rare alleles, can show whether outbreaks are related to each other rather than arriving as independent samples from the core population. The shared-allele statistic also serves as a genetic distance measure that is appropriate for small samples. These methods were applied to data on a fruit fly pest species, Bactrocera tryoni, which is quarantined from some horticultural areas in Australia. We concluded that the outbreaks in the quarantine zone came from a heterogeneous set of genetically differentiated populations, possibly ones that overwinter in the vicinity of the quarantine zone.
Phenotype-Based Identification of Mouse Chromosome Instability Mutants
Authors: Shima Naoko , Hartford Suzanne A , Duffy Ted , Wilson Lawriston A , Schimenti Kerry J , Schimenti John C 
Published: April 2021

AbstractThere is increasing evidence that defects in DNA double-strand-break (DSB) repair can cause chromosome instability, which may result in cancer. To identify novel DSB repair genes in mice, we performed a phenotype-driven mutagenesis screen for chromosome instability mutants using a flow cytometric peripheral blood micronucleus assay. Micronucleus levels were used as a quantitative indicator of chromosome damage in vivo. Among offspring derived from males mutagenized with the germline mutagen N-ethyl-N-nitrosourea (ENU), we identified a recessive mutation conferring elevated levels of spontaneous and radiation- or mitomycin C-induced micronuclei. This mutation, named chaos1 (chromosome aberration occurring spontaneously 1), was genetically mapped to a 1.3-Mb interval on chromosome 16 containing Polq, encoding DNA polymerase θ. We identified a nonconservative mutation in the ENU-derived allele, making it a strong candidate for chaos1. POLQ is homologous to Drosophila MUS308, which is essential for normal DNA interstrand crosslink repair and is unique in that it contains both a helicase and a DNA polymerase domain. While cancer susceptibility of chaos1 mutant mice is still under investigation, these data provide a practical paradigm for using a forward genetic approach to discover new potential cancer susceptibility genes using the surrogate biomarker of chromosome instability as a screen.
Sex-Specific Quantitative Trait Loci Govern Susceptibility to Theiler’s Murine Encephalomyelitis Virus-Induced Demyelination
Authors: Butterfield Russell J , Roper Randall J , Rhein Dominic M , Melvold Roger W , Haynes Lia , Ma Runlin Z , Doerge R W , Teuscher Cory 
Published: April 2021

AbstractSusceptibility to Theiler’s murine encephalomyelitis virus-induced demyelination (TMEVD), a mouse model for multiple sclerosis (MS), is genetically controlled. Through a mouse-human comparative mapping approach, identification of candidate susceptibility loci for MS based on the location of TMEVD susceptibility loci may be possible. Composite interval mapping (CIM) identified quantitative trait loci (QTL) controlling TMEVD severity in male and female backcross populations derived from susceptible DBA/2J and resistant BALBc/ByJ mice. We report QTL on chromosomes 1, 5, 15, and 16 affecting male mice. In addition, we identified two QTL in female mice located on chromosome 1. Our results support the existence of three linked sex-specific QTL on chromosome 1 with opposing effects on the severity of the clinical signs of TMEV-induced disease in male and female mice.
Group Sequential Methods and Sample Size Savings in Biomarker-Disease Association Studies
Authors: Aplenc R , Zhao H , Rebbeck T R , Propert K J 
Published: April 2021

Abstract
Molecular epidemiological association studies use valuable biosamples and incur costs. Statistical methods for early genotyping termination may conserve biosamples and costs. Group sequential methods (GSM) allow early termination of studies on the basis of interim comparisons. Simulation studies evaluated the application of GSM using data from a case-control study of GST genotypes and prostate cancer. Group sequential boundaries (GSB) were defined in the EAST-2000 software and were evaluated for study termination when early evidence suggested that the null hypothesis of no association between genotype and disease was unlikely to be rejected. Early termination of GSTM1 genotyping, which demonstrated no association with prostate cancer, occurred in &gt;90% of the simulated studies. On average, 36.4% of biosamples were saved from unnecessary genotyping. In contrast, for GSTT1, which demonstrated a positive association, inappropriate termination occurred in only 6.6%. GSM may provide significant cost and sample savings in molecular epidemiology studies.