Gene expression variation in Drosophila melanogaster due to rare transposable element insertion alleles of large effect, pp. 85–93
Julie M. Cridland, Kevin R. Thornton, and Anthony D. Long
Cridland et al. report the first genome-wide analysis of how transposable element insertions contribute to gene expression variation in a population. They examined thousands of genes with rare transposable element insertions in 37 lines from the Drosophila Genetic Reference Panel and found that presence of a transposable element within or near a gene was significantly associated with reduced gene expression. Large decreases in expression were more pronounced for insertions near genes.
A novel cholinergic action of alcohol and the development of tolerance to that effect in Caenorhabditis elegans, pp. 135–149
Edward G. Hawkins, Ian Martin, Lindsay M. Kondo, Meredith E. Judy, Victoria E. Brings, Chung-Lung Chan, GinaMari G. Blackwell, Jill C. Bettinger, and Andrew G. Davies
Better understanding the genes and mechanisms involved in acute alcohol responses might allow us to predict an individual’s predisposition to developing an alcohol use disorder. Hawkins et al. identify a novel alcohol-induced excitatory effect in C. elegans. The effect requires an acetylcholine receptor that contains the UNC-63 alpha subunit. Tolerance to the excitatory effect occurs during exposure to the drug, and this tolerance is prevented by altered function of the Sodium/Potassium transporter.
Maintenance of nucleosomal balance in cis by conserved AAA-ATPase Yta7, pp. 105–116
Laura M. Lombardi, Matthew D. Davis, and Jasper Rine
How do cells regulate the density of nucleosomes within genes? Using the highest resolution genome-wide techniques, Lombardi et al. show that the highly conserved yeast AAA-ATPase Yta7 directly promotes the proper degree of nucleosome spacing. Importantly, comprehensive double-mutant analysis demonstrates that Yta7 limits nucleosome density largely by inhibiting the histone H3/H4 chaperone Rtt106. This work identifies an important cellular antagonism which helps to maintain nucleosomal balance within genes.
Contrasting modes and tempos of venom expression evolution in two snake species, pp. 165–176
Mark J. Margres, James J. McGivern, Margaret Seavy, Kenneth P. Wray, Jack Facente, and Darin R. Rokyta
Understanding the genetic basis of adaptation requires the mapping of genotype to phenotype. To identify the processes driving patterns of phenotypic diversity, Margres et al.constructed genotype-phenotype maps and compared range-wide toxin-protein expression variation for two snake species with nearly identical ranges. Contrary to expectations, significant expression variation was only detected for one of the species. The results not only link expression variation at specific loci to divergence in a complex trait, but also have extensive conservation and biomedical implications.
A novel cryptochrome-dependent oscillator in Neurospora crassa, pp. 233–245
Imade Y. Nsa, Nirmala Karunarathna, Xiaoguang Liu, Howard Huang, Brittni Boetteger, and Deborah Bell-Pedersen
The core molecular oscillators of the conserved eukaryotic circadian clock are made up of a transcription/translation feedback loop involving clock genes. However, evidence in several model organisms suggests that the clock uses multiple molecular oscillators. Nsa et al.identified a Neurospora mutant that is rhythmic with a circadian period independent of the core FRQ/WCC oscillator. The activity of this novel oscillator requires CRYPTOCHROME, a component of the mammalian core oscillator. This mutant provides tools to unravel the complexity of the oscillator system and circadian clock evolution.
Allelic variation, aneuploidy, and nongenetic mechanisms suppress a monogenic trait in yeast, pp. 247–262
Amy Sirr, Gareth A. Cromie, Eric W. Jeffery, Teresa L. Gilbert, Catherine L. Ludlow, Adrian C. Scott, and Aimée M. Dudley
Severity of symptoms and age of onset of monogenic diseases can vary widely not only in response to environmental differences, but also due to the presence of genetic modifiers. Sirr et al. investigated the modifier genetics of a monogenic trait in a well-characterized yeast model of the human disease galactosemia. The results revealed multiple mechanisms by which the trait could be suppressed, including polymorphisms, aneuploidy of a chromosome harboring a transcriptional repressor, and a nongenetic effect.
A general unified framework to assess the sampling variance of heritability estimates using pedigree or marker-based relationships, pp. 223–232
Peter M. Visscher and Michael E. Goddard
Heritability is traditionally estimated from pedigree data by modelling the observed resemblance between relatives, and more recently, using relationships estimated from markers. Visscher and Goddard provide a single theoretical framework to calculate the asymptotic sampling variance of the heritability across a wide range of designs. The authors show that previous results are special cases of the general framework and that the variance in relationships in the sample is a key parameter in all experimental designs.
Penalized multimarker vs. single-marker regression methods for genome-wide association studies of quantitative traits, pp. 205–222
Hui Yi, Patrick Breheny, Netsanet Imam, Yongmei Liu, and Ina Hoeschele
Human genome-wide association studies (GWAS) are predominantly analyzed using single marker methods that fit an incorrect model to the data. Alternatives to Single Marker Analysis (SMA) test all or subsets of markers simultaneously and require a form of Penalized Regression. Yi et al. review Penalized Regression methods, extend them to incorporate False Discovery Rate control, investigate fusion-type penalties, assess their performance in comparison with SMA, and provide practical recommendations for the use of these methods in GWAS.