Parasex Generates Phenotypic Diversity de Novo and Impacts Drug Resistance and Virulence in Candida albicans [Genome and Systems Biology]
Candida albicans is a diploid fungus that is a frequent cause of mucosal and systemic infections in humans. This species exhibits an unusual parasexual cycle in which mating produces tetraploid cells that undergo a nonmeiotic program of concerted chromosome loss to return to a diploid or aneuploid state. In this work, we used a multipronged approach to examine the capacity of parasex to generate diversity in C. albicans. First, we compared the phenotypic properties of 32 genotyped progeny and observed wide-ranging differences in fitness, filamentation, biofilm formation, and virulence. Strikingly, one parasexual isolate di...
Source: Genetics - November 2, 2017 Category: Genetics & Stem Cells Authors: Hirakawa, M. P., Chyou, D. E., Huang, D., Slan, A. R., Bennett, R. J. Tags: Genome and Systems Biology Source Type: research
Insights into DDT Resistance from the Drosophila melanogaster Genetic Reference Panel [Genetics of Complex Traits]
Insecticide resistance is considered a classic model of microevolution, where a strong selective agent is applied to a large natural population, resulting in a change in frequency of alleles that confer resistance. While many insecticide resistance variants have been characterized at the gene level, they are typically single genes of large effect identified in highly resistant pest species. In contrast, multiple variants have been implicated in DDT resistance in Drosophila melanogaster; however, only the Cyp6g1 locus has previously been shown to be relevant to field populations. Here we use genome-wide association studies ...
Source: Genetics - November 2, 2017 Category: Genetics & Stem Cells Authors: Schmidt, J. M., Battlay, P., Gledhill-Smith, R. S., Good, R. T., Lumb, C., Fournier-Level, A., Robin, C. Tags: Genetics of Complex Traits Source Type: research
Reciprocal Genetics: Identifying QTL for General and Specific Combining Abilities in Hybrids Between Multiparental Populations from Two Maize (Zea mays L.) Heterotic Groups [Multiparental Populations]
Several plant and animal species of agricultural importance are commercialized as hybrids to take advantage of the heterosis phenomenon. Understanding the genetic architecture of hybrid performances is therefore of key importance. We developed two multiparental maize (Zea mays L.) populations, each corresponding to an important heterotic group (dent or flint) and comprised of six connected biparental segregating populations of inbred lines (802 and 822 lines for each group, respectively) issued from four founder lines. Instead of using "testers" to evaluate their hybrid values, segregating lines were crossed according to a...
Source: Genetics - November 2, 2017 Category: Genetics & Stem Cells Authors: Giraud, H., Bauland, C., Falque, M., Madur, D., Combes, V., Jamin, P., Monteil, C., Laborde, J., Palaffre, C., Gaillard, A., Blanchard, P., Charcosset, A., Moreau, L. Tags: Multiparental Populations Source Type: research
Variation in Position Effect Variegation Within a Natural Population [Genetics of Complex Traits]
Changes in chromatin state may drive changes in gene expression, and it is of growing interest to understand the population genetic forces that drive differences in chromatin state. Here, we use the phenomenon of position effect variegation (PEV), a well-studied proxy for chromatin state, to survey variation in PEV among a naturally derived population. Further, we explore the genetic architecture of natural variation in factors that modify PEV. While previous mutation screens have identified over 150 suppressors and enhancers of PEV, it remains unknown to what extent allelic variation in these modifiers mediate interindivi...
Source: Genetics - November 2, 2017 Category: Genetics & Stem Cells Authors: Kelsey, K. J. P., Clark, A. G. Tags: Genetics of Complex Traits Source Type: research
Improving Disease Prediction by Incorporating Family Disease History in Risk Prediction Models with Large-Scale Genetic Data [Genetics of Complex Traits]
Despite the many successes of genome-wide association studies (GWAS), the known susceptibility variants identified by GWAS have modest effect sizes, leading to notable skepticism about the effectiveness of building a risk prediction model from large-scale genetic data. However, in contrast to genetic variants, the family history of diseases has been largely accepted as an important risk factor in clinical diagnosis and risk prediction. Nevertheless, the complicated structures of the family history of diseases have limited their application in clinical practice. Here, we developed a new method that enables incorporation of ...
Source: Genetics - November 2, 2017 Category: Genetics & Stem Cells Authors: Gim, J., Kim, W., Kwak, S. H., Choi, H., Park, C., Park, K. S., Kwon, S., Park, T., Won, S. Tags: Genetics of Complex Traits Source Type: research
Will Big Data Close the Missing Heritability Gap? [Genomic Selection]
Despite the important discoveries reported by genome-wide association (GWA) studies, for most traits and diseases the prediction R-squared (R-sq.) achieved with genetic scores remains considerably lower than the trait heritability. Modern biobanks will soon deliver unprecedentedly large biomedical data sets: Will the advent of big data close the gap between the trait heritability and the proportion of variance that can be explained by a genomic predictor? We addressed this question using Bayesian methods and a data analysis approach that produces a surface response relating prediction R-sq. with sample size and model compl...
Source: Genetics - November 2, 2017 Category: Genetics & Stem Cells Authors: Kim, H., Grueneberg, A., Vazquez, A. I., Hsu, S., de los Campos, G. Tags: Genomic Selection Source Type: research
Prediction and Subtyping of Hypertension from Pan-Tissue Transcriptomic and Genetic Analyses [Genetics of Complex Traits]
Hypertension (HT) is a complex systemic disease involving transcriptional changes in multiple organs. Here we systematically investigate the pan-tissue transcriptional and genetic landscape of HT spanning dozens of tissues in hundreds of individuals. We find that in several tissues, previously identified HT-linked genes are dysregulated and the gene expression profile is predictive of HT. Importantly, many expression quantitative trait loci (eQTL) SNPs associated with the population variance of the dysregulated genes are linked with blood pressure in an independent genome-wide association study, suggesting that the functio...
Source: Genetics - November 2, 2017 Category: Genetics & Stem Cells Authors: Basu, M., Sharmin, M., Das, A., Nair, N. U., Wang, K., Lee, J. S., Chang, Y.-P. C., Ruppin, E., Hannenhalli, S. Tags: Genetics of Complex Traits Source Type: research
Inference of Distribution of Fitness Effects and Proportion of Adaptive Substitutions from Polymorphism Data [Population and Evolutionary Genetics]
The distribution of fitness effects (DFE) encompasses the fraction of deleterious, neutral, and beneficial mutations. It conditions the evolutionary trajectory of populations, as well as the rate of adaptive molecular evolution (α). Inferring DFE and α from patterns of polymorphism, as given through the site frequency spectrum (SFS) and divergence data, has been a longstanding goal of evolutionary genetics. A widespread assumption shared by previous inference methods is that beneficial mutations only contribute negligibly to the polymorphism data. Hence, a DFE comprising only deleterious mutations tends to be e...
Source: Genetics - November 2, 2017 Category: Genetics & Stem Cells Authors: Tataru, P., Mollion, M., Glemin, S., Bataillon, T. Tags: Population and Evolutionary Genetics Source Type: research
Donor-Recipient Identification in Para- and Poly-phyletic Trees Under Alternative HIV-1 Transmission Hypotheses Using Approximate Bayesian Computation [Population and Evolutionary Genetics]
Diversity of the founding population of Human Immunodeficiency Virus Type 1 (HIV-1) transmissions raises many important biological, clinical, and epidemiological issues. In up to 40% of sexual infections, there is clear evidence for multiple founding variants, which can influence the efficacy of putative prevention methods, and the reconstruction of epidemiologic histories. To infer who-infected-whom, and to compute the probability of alternative transmission scenarios while explicitly taking phylogenetic uncertainty into account, we created an approximate Bayesian computation (ABC) method based on a set of statistics meas...
Source: Genetics - November 2, 2017 Category: Genetics & Stem Cells Authors: Romero-Severson, E. O., Bulla, I., Hengartner, N., Bartolo, I., Abecasis, A., Azevedo-Pereira, J. M., Taveira, N., Leitner, T. Tags: Population and Evolutionary Genetics Source Type: research
Mitigating Mitochondrial Genome Erosion Without Recombination [Population and Evolutionary Genetics]
Mitochondria are ATP-producing organelles of bacterial ancestry that played a key role in the origin and early evolution of complex eukaryotic cells. Most modern eukaryotes transmit mitochondrial genes uniparentally, often without recombination among genetically divergent organelles. While this asymmetric inheritance maintains the efficacy of purifying selection at the level of the cell, the absence of recombination could also make the genome susceptible to Muller’s ratchet. How mitochondria escape this irreversible defect accumulation is a fundamental unsolved question. Occasional paternal leakage could in principle...
Source: Genetics - November 2, 2017 Category: Genetics & Stem Cells Authors: Radzvilavicius, A. L., Kokko, H., Christie, J. R. Tags: Population and Evolutionary Genetics Source Type: research
Tra-2 Mediates Cross-Talk Between Sex Determination and Wing Polyphenism in Female Nilaparvata lugens [Developmental and Behavioral Genetics]
Sexual dimorphism and wing polyphenism are important and evolutionarily conserved features of many insect species. In this article, we found a cross-talk linking sexual differentiation with wing polyphenism in the brown planthopper (BPH) Nilaparvata lugens (order: Hemiptera). Knockdown of the sex determination gene Transformer-2 in N. lugens (NlTra-2) in nymph caused females to develop into infertile pseudomales containing undeveloped ovaries. Whereas males treated with dsNlTra-2 exhibited normal morphology, but lost fertility. Knockdown of NlTra-2 in adult females (maternal RNAi) resulted in long-winged female offspring, ...
Source: Genetics - November 2, 2017 Category: Genetics & Stem Cells Authors: Zhuo, J.-C., Lei, C., Shi, J.-K., Xu, N., Xue, W.-H., Zhang, M.-Q., Ren, Z.-W., Zhang, H.-H., Zhang, C.-X. Tags: Developmental and Behavioral Genetics Source Type: research
Body Shape and Coloration of Silkworm Larvae Are Influenced by a Novel Cuticular Protein [Developmental and Behavioral Genetics]
The genetic basis of body shape and coloration patterns on caterpillars is often assumed to be regulated separately, but it is possible that common molecules affect both types of trait simultaneously. Here we examine the genetic basis of a spontaneous cuticle defect in silkworm, where larvae exhibit a bamboo-like body shape and decreased pigmentation. We performed linkage mapping and mutation screening to determine the gene product that affects body shape and coloration simultaneously. In these mutant larvae we identified a null mutation in BmorCPH24, a gene encoding a cuticular protein with low complexity sequence. Spatio...
Source: Genetics - November 2, 2017 Category: Genetics & Stem Cells Authors: Xiong, G., Tong, X., Gai, T., Li, C., Qiao, L., Monteiro, A., Hu, H., Han, M., Ding, X., Wu, S., Xiang, Z., Lu, C., Dai, F. Tags: Developmental and Behavioral Genetics Source Type: research
Apico-basal Polarity Determinants Encoded by crumbs Genes Affect Ciliary Shaft Protein Composition, IFT Movement Dynamics, and Cilia Length [Developmental and Behavioral Genetics]
One of the most obvious manifestations of polarity in epithelia is the subdivision of the cell surface by cell junctions into apical and basolateral domains. crumbs genes are among key regulators of this form of polarity. Loss of crumbs function disrupts the apical cell junction belt and crumbs overexpression expands the apical membrane size. Crumbs proteins contain a single transmembrane domain and localize to cell junction area at the apical surface of epithelia. In some tissues, they are also found in cilia. To test their role in ciliogenesis, we investigated mutant phenotypes of zebrafish crumbs genes. In zebrafish, mu...
Source: Genetics - November 2, 2017 Category: Genetics & Stem Cells Authors: Hazime, K., Malicki, J. J. Tags: Developmental and Behavioral Genetics Source Type: research
Ethanol Stimulates Locomotion via a G{alpha}s-Signaling Pathway in IL2 Neurons in Caenorhabditis elegans [Cellular Genetics]
Alcohol is a potent pharmacological agent when consumed acutely at sufficient quantities and repeated overuse can lead to addiction and deleterious effects on health. Alcohol is thought to modulate neuronal function through low-affinity interactions with proteins, in particular with membrane channels and receptors. Paradoxically, alcohol acts as both a stimulant and a sedative. The exact molecular mechanisms for the acute effects of ethanol on neurons, as either a stimulant or a sedative, however remain unclear. We investigated the role that the heat shock transcription factor HSF-1 played in determining a stimulatory phen...
Source: Genetics - November 2, 2017 Category: Genetics & Stem Cells Authors: Johnson, J. R., Edwards, M. R., Davies, H., Newman, D., Holden, W., Jenkins, R. E., Burgoyne, R. D., Lucas, R. J., Barclay, J. W. Tags: Cellular Genetics Source Type: research
Distinct and Cooperative Roles of amh and dmrt1 in Self-Renewal and Differentiation of Male Germ Cells in Zebrafish [Genetics of Sex]
In this study, we examined the roles of amh and dmrt1 in male germ cell development by generating their mutants with Crispr/Cas9 technology in zebrafish. Amh mutant zebrafish displayed a female-biased sex ratio, and both male and female amh mutants developed hypertrophic gonads due to uncontrolled proliferation and impaired differentiation of germ cells. A large number of proliferating spermatogonium-like cells were observed within testicular lobules of the amh-mutated testes, and they were demonstrated to be both Vasa- and PH3-positive. Moreover, the average number of Sycp3- and Vasa-positive cells in the amh mutants was ...
Source: Genetics - November 2, 2017 Category: Genetics & Stem Cells Authors: Lin, Q., Mei, J., Li, Z., Zhang, X., Zhou, L., Gui, J.-F. Tags: Genetics of Sex Source Type: research
