bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inbreeding and the Genetic Complexity of Human Hypertension
Authors: Rudan Igor , Smolej-Narancic Nina , Campbell Harry , Carothers Andrew , Wright Alan , Janicijevic Branka , Rudan Pavao 
Published: April 2021

Abstract
Considerable uncertainty exists regarding the genetic architecture underlying common late-onset human diseases. In particular, the contribution of deleterious recessive alleles has been predicted to be greater for late-onset than for early-onset traits. We have investigated the contribution of recessive alleles to human hypertension by examining the effects of inbreeding on blood pressure (BP) as a quantitative trait in 2760 adult individuals from 25 villages within Croatian island isolates. We found a strong linear relationship between the inbreeding coefficient (F) and both systolic and diastolic BP, indicating that recessive or partially recessive quantitative trait locus (QTL) alleles account for 10-15% of the total variation in BP in this population. An increase in F of 0.01 corresponded to an increase of ∼3 mm Hg in systolic and 2 mm Hg in diastolic BP. Regression of F on BP indicated that at least several hundred (300-600) recessive QTL contribute to BP variability. A model of the distribution of locus effects suggests that the 8-16 QTL of largest effect together account for a maximum of 25% of the dominance variation, while the remaining 75% of the variation is mediated by QTL of very small effect, unlikely to be detectable using current technologies and sample sizes. We infer that recent inbreeding accounts for 36% of all hypertension in this population. The global impact of inbreeding on hypertension may be substantial since, although inbreeding is declining in Western societies, an estimated 1 billion people globally show rates of consanguineous marriages &gt;20%.
Analyses for the Presence of a Major Gene Affecting Uterine Capacity in Unilaterally Ovariectomized Rabbits
Authors: Argente M J , Blasco A , Ortega J A , Haley C S , Visscher P M 
Published: April 2021

AbstractThe presence of a major gene for uterine capacity (UC), ovulation rate (OR), number of implanted embryos (IE), embryo survival (ES), fetal survival (FS), and prenatal survival (PS) was investigated in a population of rabbits divergently selected for UC for 10 generations. Selection was performed on estimated breeding values for UC up to four parities. UC was estimated as litter size in the remaining overcrowded horn of unilaterally ovariectomized does. OR and IE were counted by means of laparoscopy. Bartlett’s test, Fain’s test, and a complex segregation analysis using Bayesian methods were used to test for the presence of a major gene. All three tests showed that the data appeared consistent with the presence of a major gene affecting UC and IE. The results of the complex segregation analysis suggested the presence of a major gene with large effect on IE and ES (a &gt; 1σp), at high frequency (p = 0.70 and 0.68, respectively), and with a large contribution to the total variance (Rg = 0.39 and 0.47, respectively); and the presence of a major gene with moderate effect on each of OR, FS, PS, and UC. The results suggest that the studied reproductive traits are determined genetically by at least one gene of large effect.
Single-Nucleotide Polymorphisms in Soybean
Authors: Zhu Y L , Song Q J , Hyten D L , Van Tassell C P , Matukumalli L K , Grimm D R , Hyatt S M , Fickus E W , Young N D , Cregan P B 
Published: April 2021

Abstract
Single-nucleotide polymorphisms (SNPs) provide an abundant source of DNA polymorphisms in a number of eukaryotic species. Information on the frequency, nature, and distribution of SNPs in plant genomes is limited. Thus, our objectives were (1) to determine SNP frequency in coding and noncoding soybean (Glycine max L. Merr.) DNA sequence amplified from genomic DNA using PCR primers designed to complete genes, cDNAs, and random genomic sequence; (2) to characterize haplotype variation in these sequences; and (3) to provide initial estimates of linkage disequilibrium (LD) in soybean. Approximately 28.7 kbp of coding sequence, 37.9 kbp of noncoding perigenic DNA, and 9.7 kbp of random noncoding genomic DNA were sequenced in each of 25 diverse soybean genotypes. Over the &gt;76 kbp, mean nucleotide diversity expressed as Watterson’s θ was 0.00097. Nucleotide diversity was 0.00053 and 0.00111 in coding and in noncoding perigenic DNA, respectively, lower than estimates in the autogamous model species Arabidopsis thaliana. Haplotype analysis of SNP-containing fragments revealed a deficiency of haplotypes vs. the number that would be anticipated at linkage equilibrium. In 49 fragments with three or more SNPs, five haplotypes were present in one fragment while four or less were present in the remaining 48, thereby supporting the suggestion of relatively limited genetic variation in cultivated soybean. Squared allele-frequency correlations (r2) among haplotypes at 54 loci with two or more SNPs indicated low genome-wide LD. The low level of LD and the limited haplotype diversity suggested that the genome of any given soybean accession is a mosaic of three or four haplotypes. To facilitate SNP discovery and the development of a transcript map, subsets of four to six diverse genotypes, whose sequence analysis would permit the discovery of at least 75% of all SNPs present in the 25 genotypes as well as 90% of the common (frequency &gt;0.10) SNPs, were identified.
Neutrality Tests Using DNA Polymorphism From Multiple Samples
Authors: Li Haipeng , Zhang Yunwu , Zhang Ya-Ping , Fu Yun-Xin 
Published: April 2021

Abstract
The polymorphism of a gene or a locus is studied with increasing frequency by multiple laboratories or the same group at different times. Such practice results in polymorphism being revealed by different samples at different regions of the locus. Tests of neutrality have been widely conducted for polymorphism data but commonly used statistical tests cannot be applied directly to such data. This article provides a procedure to conduct a neutrality test and details are given for two commonly used tests. Applying the two new tests to the chemokine-receptor gene (CCR5) in humans, we found that the hypothesis that all mutations are selectively neutral cannot explain the observed pattern of DNA polymorphism.
Mapping Quantitative Trait Loci in the Case of a Spike in the Phenotype Distribution
Authors: Broman Karl W 
Published: April 2021

AbstractA common departure from the usual normality assumption in QTL mapping concerns a spike in the phenotype distribution. For example, in measurements of tumor mass, some individuals may exhibit no tumors; in measurements of time to death after a bacterial infection, some individuals may recover from the infection and fail to die. If an appreciable portion of individuals share a common phenotype value (generally either the minimum or the maximum observed phenotype), the standard approach to QTL mapping can behave poorly. We describe several alternative approaches for QTL mapping in the case of such a spike in the phenotype distribution, including the use of a two-part parametric model and a nonparametric approach based on the Kruskal-Wallis test. The performance of the proposed procedures is assessed via computer simulation. The procedures are further illustrated with data from an intercross experiment to identify QTL contributing to variation in survival of mice following infection with Listeria monocytogenes.
Bayesian Sperm Competition Estimates
Authors: Jones Beatrix , Clark Andrew G 
Published: April 2021

Abstract
We introduce a Bayesian method for estimating parameters for a model of multiple mating and sperm displacement from genotype counts of brood-structured data. The model is initially targeted for Drosophila melanogaster, but is easily adapted to other organisms. The method is appropriate for use with field studies where the number of mates and the genotypes of the mates cannot be controlled, but where unlinked markers have been collected for a set of females and a sample of their offspring. Advantages over previous approaches include full use of multilocus information and the ability to cope appropriately with missing data and ambiguities about which alleles are maternally vs. paternally inherited. The advantages of including X-linked markers are also demonstrated.
Ku-Dependent and Ku-Independent End-Joining Pathways Lead to Chromosomal Rearrangements During Double-Strand Break Repair in Saccharomyces cerevisiae
Authors: Yu Xin , Gabriel Abram 
Published: April 2021

Abstract
Chromosomal double-strand breaks (DSBs) can be repaired by either homology-dependent or homology-independent pathways. Nonhomologous repair mechanisms have been relatively less well studied, despite their potential importance in generating chromosomal rearrangements. We have developed a Saccharomyces cerevisiae-based assay to identify and characterize homology-independent chromosomal rearrangements associated with repair of a unique DSB generated within an engineered URA3 gene. Approximately 1% of successfully repaired cells have accompanying chromosomal rearrangements consisting of large insertions, deletions, aberrant gene conversions, or other more complex changes. We have analyzed rearrangements in isogenic wild-type, rad52, yku80, and rad52 yku80 strains, to determine the types of events that occur in the presence or absence of these key repair proteins. Deletions were found in all strain backgrounds, but insertions were dependent upon the presence of Yku80p. A rare RAD52- and YKU80-independent form of deletion was present in all strains. These events were characterized by long one-sided deletions (up to 13 kb) and extensive imperfect overlapping sequences (7-22 bp) at the junctions. Our results demonstrate that the frequency and types of repair events depend on the specific genetic context. This approach can be applied to a number of problems associated with chromosome stability.
DIM-1, a Novel Immunoglobulin Superfamily Protein in Caenorhabditis elegans, Is Necessary for Maintaining Bodywall Muscle Integrity
Authors: Rogalski Teresa M , Gilbert Mary M , Devenport Danelle , Norman Kenneth R , Moerman Donald G 
Published: April 2021

Abstract
The UNC-112 protein is required during initial muscle assembly in C. elegans to form dense bodies and M-lines. Loss of this protein results in arrest at the twofold stage of embryogenesis. In contrast, a missense mutation in unc-112 results in viable animals that have disorganized bodywall muscle and are paralyzed as adults. Loss or reduction of dim-1 gene function can suppress the severe muscle disruption and paralysis exhibited by these mutant hermaphrodites. The overall muscle structure in hermaphrodites lacking a functional dim-1 gene is slightly disorganized, and the myofilament lattice is not as strongly anchored to the muscle cell membrane as it is in wild-type muscle. The dim-1 gene encodes two polypeptides that contain three Ig-like repeats. The short DIM-1 protein isoform consists entirely of three Ig repeats and is sufficient for wild-type bodywall muscle structure and stability. DIM-1(S) localizes to the region of the muscle cell membrane around and between the dense bodies, which are the structures that anchor the actin filaments and may play a role in stabilizing the thin rather than the thick filament components of the sarcomere.
Mapping by Sequencing the Pneumocystis Genome Using the Ordering DNA Sequences V3 Tool
Authors: Xu Zheng , Lance Britton , Vargas Claudia , Arpinar Budak , Bhandarkar Suchendra , Kraemer Eileen , Kochut Krys J , Miller John A , Wagner Jeff R , Weise Michael J , Wunderlich John K , Stringer James , Smulian George , Cushion Melanie T , Arnold Jonathan 
Published: April 2021

Abstract
A bioinformatics tool called ODS3 has been created for mapping by sequencing. The tool allows the creation of integrated genomic maps from genetic, physical mapping, and sequencing data and permits an integrated genome map to be stored, retrieved, viewed, and queried in a stand-alone capacity, in a client/server relationship with the Fungal Genome Database (FGDB), and as a web-browsing tool for the FGDB. In that ODS3 is programmed in Java, the tool promotes platform independence and supports export of integrated genome-mapping data in the extensible markup language (XML) for data interchange with other genome information systems. The tool ODS3 is used to create an initial integrated genome map of the AIDS-related fungal pathogen, Pneumocystis carinii. Contig dynamics would indicate that this physical map is ∼50% complete with ∼200 contigs. A total of 10 putative multigene families were found. Two of these putative families were previously characterized in P. carinii, namely the major surface glycoproteins (MSGs) and HSP70 proteins; three of these putative families (not previously characterized in P. carinii) were found to be similar to families encoding the HSP60 in Schizosaccharomyces pombe, the heat-shock Ψ protein in S. pombe, and the RNA synthetase family (i.e., MES1) in Saccharomyces cerevisiae. Physical mapping data are consistent with the 16S, 5.8S, and 26S rDNA genes being single copy in P. carinii. No other fungus outside this genus is known to have the rDNA genes in single copy.
Drosophila Tufted Is a Gain-of-Function Allele of the Proneural Gene amos
Authors: Lai Eric C 
Published: April 2021

Abstract
Tufted is a classical Drosophila mutant characterized by a large number of ectopic mechanosensory bristles on the dorsal mesothorax. Unlike other ectopic bristle mutants, Tufted is epistatic to achaete and scute, the proneural genes that normally control the development of these sensory organs. In this report, I present genetic and molecular evidence that Tufted is a gain-of-function allele of the proneural gene amos that ectopically activates mechanosensory neurogenesis. I also systematically examine the ability of the various proneural bHLH proteins to cross-activate each other and find that their ability to do so is in general relatively limited, despite their common ability to induce the formation of mechanosensory bristles. This phenomenon seems instead to be related to their shared ability to activate Asense and Senseless.
A Genetic Screen for Hedgehog Targets Involved in the Maintenance of the Drosophila Anteroposterior Compartment Boundary
Authors: Végh Mátyás , Basler Konrad 
Published: April 2021

Abstract
The development of multicellular organisms requires the establishment of cell populations with different adhesion properties. In Drosophila, a cell-segregation mechanism underlies the maintenance of the anterior (A) and posterior (P) compartments of the wing imaginal disc. Although engrailed (en) activity contributes to the specification of the differential cell affinity between A and P cells, recent evidence suggests that cell sorting depends largely on the transduction of the Hh signal in A cells. The activator form of Cubitus interruptus (Ci), a transcription factor mediating Hh signaling, defines anterior specificity, indicating that Hh-dependent cell sorting requires Hh target gene expression. However, the identity of the gene(s) contributing to distinct A and P cell affinities is unknown. Here, we report a genetic screen based on the FRT/FLP system to search for genes involved in the correct establishment of the anteroposterior compartment boundary. By using double FRT chromosomes in combination with a wing-specific FLP source we screened 250,000 mutagenized chromosomes. Several complementation groups affecting wing patterning have been isolated, including new alleles of most known Hh-signaling components. Among these, we identified a class of patched (ptc) alleles exhibiting a novel phenotype. These results demonstrate the value of our setup in the identification of genes involved in distinct wing-patterning processes.
Mutation Rate and Novel tt Mutants of Arabidopsis thaliana Induced by Carbon Ions
Authors: Shikazono Naoya , Yokota Yukihiko , Kitamura Satoshi , Suzuki Chihiro , Watanabe Hiroshi , Tano Shigemitsu , Tanaka Atsushi 
Published: April 2021

Abstract
Irradiation of Arabidopsis thaliana by carbon ions was carried out to investigate the mutational effect of ion particles in higher plants. Frequencies of embryonic lethals and chlorophyll-deficient mutants were found to be significantly higher after carbon-ion irradiation than after electron irradiation (11-fold and 7.8-fold per unit dose, respectively). To estimate the mutation rate of carbon ions, mutants with no pigments on leaves and stems (tt) and no trichomes on leaves (gl) were isolated at the M2 generation and subjected to analysis. Averaged segregation rate of the backcrossed mutants was 0.25, which suggested that large deletions reducing the viability of the gametophytes were not transmitted, if generated, in most cases. During the isolation of mutants, two new classes of flavonoid mutants (tt18, tt19) were isolated from carbon-ion-mutagenized M2 plants. From PCR and sequence analysis, two of the three tt18 mutant alleles were found to have a small deletion within the LDOX gene and the other was revealed to contain a rearrangement. Using the segregation rates, the mutation rate of carbon ions was estimated to be 17-fold higher than that of electrons. The isolation of novel mutants and the high mutation rate suggest that ion particles can be used as a valuable mutagen for plant genetics.
The Quality Measures Domain in Nursing Home Compare: Is High Performance Meaningful or Misleading?
Authors: Konetzka R Tamara , Davila Heather , Brauner Daniel J , Cursio John F , Sharma Hari , Werner Rachel M , Park Young Shin , Shippee Tetyana P 
Published: April 2021

Abstract

Background and Objectives
The reported percent of nursing home residents suffering adverse outcomes decreased dramatically since Nursing Home Compare began reporting them, but the validity of scores is questionable for nursing homes that score well on measures using facility-reported data but poorly on inspections. Our objective was to assess whether nursing homes with these “discordant” scores are meaningfully better than nursing homes that score poorly across domains.

Research Design and Methods
We used a convergent mixed-methods design, starting with quantitative analyses of 2012–2016 national data. We conducted in-depth interviews and observations in 12 nursing homes in 2017–2018, focusing on how facilities achieved their Nursing Home Compare ratings. Additional quantitative analyses were conducted in parallel to study performance trajectories over time. Quantitative and qualitative results were interpreted together.

Results
Discordant facilities engage in more quality improvement strategies than poor performers, but do not seem to invest in quality improvement in resource-intensive, broad-based ways that would spill over into other domains of quality and change their trajectory of improvement. Instead, they focus on lower-resource improvements related to data quality, staff training, leadership, and communication. In contrast, poor-performing facilities seemed to lack the leadership and continuity of staff required for even these low-resource interventions.

Discussion and Implications
High performance on the quality measures using facility-reported data is mostly meaningful rather than misleading to consumers who care about those outcomes, although discordant facilities still have quality deficits. The quality measures domain should continue to have a role in Nursing Home Compare.
A cross-tissue transcriptome-wide association study identifies novel susceptibility genes for lung cancer in Chinese populations
Authors: Zhu Meng , Fan Jingyi , Zhang Chang , Xu Jing , Yin Rong , Zhang Erbao , Wang Yuzhuo , Ji Mengmeng , Sun Qi , Dai Juncheng , Jin Guangfu , Chen Liang , Xu Lin , Hu Zhibin , Ma Hongxia , Shen Hongbing 
Published: April 2021

Abstract
Although dozens of susceptibility loci have been identified for lung cancer in genome-wide association studies (GWASs), the susceptibility genes and underlying mechanisms remain unclear. In this study, we conducted a cross-tissue transcriptome-wide association study (TWAS) with UTMOST based on summary statistics from 13 327 lung cancer cases and 13 328 controls and the genetic-expression matrix over 44 human tissues in the Genotype-Tissue Expression (GTEx) project. After further evaluating the associations in each tissue, we revealed 6 susceptibility genes in known loci and identified 12 novel ones. Among those, five novel genes, including DCAF16 (Pcross-tissue = 2.57 × 10−5, PLung = 2.89 × 10−5), CBL (Pcross-tissue = 5.08 × 10−7, PLung = 1.82 × 10−4), ATR (Pcross-tissue = 1.45 × 10−5, PLung = 9.68 × 10−5), GYPE (Pcross-tissue = 1.45 × 10−5, PLung = 2.17 × 10−3) and PARD3 (Pcross-tissue = 5.79 × 10−6, PLung = 4.05 × 10−3), were significantly associated with the risk of lung cancer in both cross-tissue and lung tissue models. Further colocalization analysis indicated that rs7667864 (C &gt; A) and rs2298650 (G &gt; T) drove the GWAS association signals at 4p15.31–32 (OR = 1.09, 95%CI: 1.04–1.12, PGWAS = 5.54 × 10−5) and 11q23.3 (OR = 1.08, 95%CI: 1.04–1.13, PGWAS = 5.55 × 10−5), as well as the expression of DCAF16 (βGTEx = 0.24, PGTEx = 9.81 × 10−15; βNJLCC = 0.29, PNJLCC = 3.84 × 10−8) and CBL (βGTEx = −0.17, PGTEx = 2.82 × 10−8; βNJLCC = −0.32, PNJLCC = 2.61 × 10−7) in lung tissue. Functional annotations and phenotype assays supported the carcinogenic effect of these novel susceptibility genes in lung carcinogenesis.