Simultaneous modeling of disease status and clinical phenotypes to increase power in genome-wide association studies, pp. 1041-1047
Michael Bilow, Fernando Crespo, Zhicheng Pan, Eleazar Eskin, and Susana Eyheramendy
Jointly modeling clinical phenotype and disease status is a promising way to increase power to detect true associations between genetics and disease in genome-wide association studies. However, standard multivariate techniques fail to effectively solve this problem because their case-control status is discrete and not continuous. Standard approaches to estimate model parameters suffer ascertainment bias in case/control studies. The authors present a novel method that resolves both of these issues for simultaneous association testing of genetic variants that have both case status and a clinical covariate.
Inferring individual inbreeding and demographic history from segments of identity by descent in Ficedula flycatcher genome sequences, pp. 1319-1334
Marty Kardos, Anna Qvarnström, and Hans Ellegren
Individual inbreeding and historical demography can be estimated by analyzing runs of homozygosity (ROH), which are indicative of identity by descent (IBD). Such analyses have so far been rare in natural populations due to limited genomic resources. Kardos et al. analyzed ROH in Ficedula flycatchers. The strongest contributors to genome-wide variation in ROH abundance were likely positive selection and increased power to detect ROH in regions with low recombination. The authors identified populations with particularly small effective population size (Ne) and estimated the size and founding time of an island population.
The relative contributions of the X chromosome and autosomes to local adaptation, pp. 1285-1304
Clémentine Lasne, Carla M. Sgrò, and Tim Connallon
Environmental conditions vary across species’ ranges, leading to natural selection for local adaptation. Nevertheless, gene flow constrains population differentiation, and may influence the genetic architecture of locally adapted phenotypes. Lasne et al. develop new models that explicitly quantify the roles of the X chromosome and autosomes in adaptation to local environmental conditions. They identify a broad scope for large-X effects in local adaptation, with X-linked inheritance enhancing adaptation to local conditions. The theory yields new predictions about the genetic architecture of local adaptation, and the genomic basis of evolutionary differentiation between populations of geographically widespread species.
Sexual dimorphism of body size is controlled by dosage of the X-chromosomal gene Myc and by the sex-determining gene tra in Drosophila, pp. 1215-1228
Kristina Wehr Mathews, Margrith Cavegn, and Monica Zwicky
Sexual dimorphism of body size is prevalent throughout the animal kingdom. Drosophila females are larger than males and a central gene of the sex-determination pathway, transformer (tra), contributes to this difference. The authors have now identified another potent regulator of size dimorphism, showing that dosage of the Myc gene regulates sex-specific growth together with tra. By escaping dosage compensation, Myc confers a growth advantage to females. Since Myc is also involved in the activation of tra, this gene is a key player in the control of sex-specific body size.
Nutritional control of chronological aging and heterochromatin in Saccharomyces cerevisiae, pp. 1179-1193
David F. McCleary and Jasper Rine
The role of Sirtuins in lifespan extension via calorie restriction (CR) in Saccharomyces cerevisiae is controversial. The authors measured chronological lifespan over a higher glucose range than typically used for studying yeast CR in minimal and rich media. In minimal medium, sir2Δ extended lifespan in high glucose with little effect in low glucose. In rich medium, sir2Δ decreased lifespan in low glucose with little effect in high glucose. In minimal medium, increasing glucose stabilized Sir-based silencing at HML, while, in rich medium, it destabilized silencing.
Chromatin regulation by the NuA4 acetyltransferase complex is mediated by essential interactions between enhancer of polycomb (Epl1) and Esa1, pp. 1125-1137
Naomi E. Searle, Ana Lilia Torres-Machorro, and Lorraine Pillus
Uncovering functions for non-catalytic subunits of macromolecular complexes is a major challenge. Enhancer of Polycomb is a deeply conserved protein with clear roles in development and cancer but it is unclear what role it plays in vivo within the NuA4 acetyltransferase complex. The authors engineered yeast genetic landscapes for cells to survive without EPL1 and in so doing, define Epl1 as a key co-factor for the essential catalytic enzyme of NuA4, Esa1. Despite having no acetyltransferase activity itself, they show that Epl1 is as critically important as Esa1 in genomic regulation.
Meiotic crossing over in maize knob heterochromatin, pp. 1101-1112
Stephen M. Stack, Lindsay A. Shearer, Leslie Lohmiller, and Lorinda K. Anderson
Crossing over is suppressed in the heterochromatin associated with centromeres and nucleolus organizers. But is this characteristic of all heterochromatin? Stack et al. examined meiotic recombination in maize knob heterochromatin. They found knob heterochromatin does not suppress crossing over when considered per unit of syn- aptonemal complex length. However, because the amount of DNA in knob heterochromatin is much higher, crossing over is suppressed in terms of genetic length per DNA amount.
Efficient estimation of realized kinship from single nucleotide polymorphism genotypes, pp. 1063-1078
Bowen Wang, Serge Sverdlov, and Elizabeth Thompson
Realized kinship has become an important component of many genetic analyses, including heritability estimation and genomic prediction. It is widely used both in human genetics and in analyses of livestock and plant populations. This paper considers estimators of realized kinship from SNP genotypes, and proposes two new estimators. The authors show that improved estimators are obtained by: optimal weighting of markers, taking physical contiguity of the genome into account, and weighting on the basis of LD.
This Month in the American Journal of Human Genetics
Who's who? Detecting and resolving sample anomalies in human DNA sequencing studies with peddy. Am. J. Hum. Genet. 100(3); 10.1016/j.ajhg.2017.01.017
Brent S. Pedersen and Aaron R. Quinlan
Advances in DNA technology have made it possible to answer diverse questions related to human health and history. But as with any process involving human intervention, the potential utility of this technology can be hampered by errors such as contamination or mislabeling. While laboratory best practices certainly are recommended, there is also a need to improve the ability to detect and correct handling errors. In presenting peddy, Pedersen and Quinlan do just that. Their fast and user-friendly software analyzes pedigree files for a variety of errors, as well as metrics of poor sequencing quality, and presents results in an interactive format that enables clear communication and rapid remediation of common sequencing pitfalls.
In CBE — Life Sciences Education (LSE)
Making the grade: using instructional feedback and evaluation to inspire evidence-based teaching, CBE-Life Sci. Educ. vol 15(4), ar75.
Peggy Brickman, Cara Gormally, and Amedee Marchand Martella
Education research has identified evidence-based methods for fostering better teaching and learning, but do current teaching evaluation practices offer supportive guidance and feedback in the use of such techniques? Brickman, et al. reviewed current practices in teaching evaluations through a national survey of faculty. Though reported as most useful, teaching evaluations by faculty peers were less common than student evaluations, especially at research institutions. Faculty requested constructive peer feedback that was rigorous, frequent, and formative; they also prefer to choose their evaluator, preferably one with education research experience. The authors state that improved teaching evaluation may be “the missing link” for expanding implementation of evidence-based teaching.
- Copyright © 2017 by the Genetics Society of America