A Bayesian Approach for Analysis of Whole-Genome Bisulfite Sequencing Data Identifies Disease-Associated Changes in DNA Methylation [Statistical Genetics and Genomics]
DNA methylation is a key epigenetic modification involved in gene regulation whose contribution to disease susceptibility remains to be fully understood. Here, we present a novel Bayesian smoothing approach (called ABBA) to detect differentially methylated regions (DMRs) from whole-genome bisulfite sequencing (WGBS). We also show how this approach can be leveraged to identify disease-associated changes in DNA methylation, suggesting mechanisms through which these alterations might affect disease. From a data modeling perspective, ABBA has the distinctive feature of automatically adapting to different correlation structures...
Source: Genetics - March 30, 2017 Category: Genetics & Stem Cells Authors: Rackham, O. J. L., Langley, S. R., Oates, T., Vradi, E., Harmston, N., Srivastava, P. K., Behmoaras, J., Dellaportas, P., Bottolo, L., Petretto, E. Tags: Statistical Genetics and Genomics Source Type: research
Genomic Rearrangements in Arabidopsis Considered as Quantitative Traits [Statistical Genetics and Genomics]
To understand the population genetics of structural variants and their effects on phenotypes, we developed an approach to mapping structural variants that segregate in a population sequenced at low coverage. We avoid calling structural variants directly. Instead, the evidence for a potential structural variant at a locus is indicated by variation in the counts of short-reads that map anomalously to that locus. These structural variant traits are treated as quantitative traits and mapped genetically, analogously to a gene expression study. Association between a structural variant trait at one locus, and genotypes at a dista...
Source: Genetics - March 30, 2017 Category: Genetics & Stem Cells Authors: Imprialou, M., Kahles, A., Steffen, J. G., Osborne, E. J., Gan, X., Lempe, J., Bhomra, A., Belfield, E., Visscher, A., Greenhalgh, R., Harberd, N. P., Goram, R., Hein, J., Robert-Seilaniantz, A., Jones, J., Stegle, O., Kover, P., Tsiantis, M., Nordborg, M Tags: Statistical Genetics and Genomics Source Type: research
The Predicted Cross Value for Genetic Introgression of Multiple Alleles [Statistical Genetics and Genomics]
We consider the plant genetic improvement challenge of introgressing multiple alleles from a homozygous donor to a recipient. First, we frame the project as an algorithmic process that can be mathematically formulated. We then introduce a novel metric for selecting breeding parents that we refer to as the predicted cross value (PCV). Unlike estimated breeding values, which represent predictions of general combining ability, the PCV predicts specific combining ability. The PCV takes estimates of recombination frequencies as an input vector and calculates the probability that a pair of parents will produce a gamete with desi...
Source: Genetics - March 30, 2017 Category: Genetics & Stem Cells Authors: Han, Y., Cameron, J. N., Wang, L., Beavis, W. D. Tags: Statistical Genetics and Genomics Source Type: research
Second-Generation Drosophila Chemical Tags: Sensitivity, Versatility, and Speed [Methods, Technology, and Resources]
Labeling and visualizing cells and subcellular structures within thick tissues, whole organs, and even intact animals is key to studying biological processes. This is particularly true for studies of neural circuits where neurons form submicron synapses but have arbors that may span millimeters in length. Traditionally, labeling is achieved by immunofluorescence; however, diffusion of antibody molecules (>100 kDa) is slow and often results in uneven labeling with very poor penetration into the center of thick specimens; these limitations can be partially addressed by extending staining protocols to over a week (Drosophi...
Source: Genetics - March 30, 2017 Category: Genetics & Stem Cells Authors: Sutcliffe, B., Ng, J., Auer, T. O., Pasche, M., Benton, R., Jefferis, G. S. X. E., Cachero, S. Tags: Methods, Technology, and Resources Source Type: research
Circadian Rhythms and Sleep in Drosophila melanogaster [Nervous System and Behaviour]
The advantages of the model organism Drosophila melanogaster, including low genetic redundancy, functional simplicity, and the ability to conduct large-scale genetic screens, have been essential for understanding the molecular nature of circadian (~24 hr) rhythms, and continue to be valuable in discovering novel regulators of circadian rhythms and sleep. In this review, we discuss the current understanding of these interrelated biological processes in Drosophila and the wider implications of this research. Clock genes period and timeless were first discovered in large-scale Drosophila genetic screens developed in the ...
Source: Genetics - March 30, 2017 Category: Genetics & Stem Cells Authors: Dubowy, C., Sehgal, A. Tags: Nervous System and Behaviour Source Type: research
Mitochondrial Replacement Therapy: Are Mito-nuclear Interactions Likely To Be a Problem? [Review]
It has been suggested that deleterious interactions between the mitochondrial and nuclear genomes could pose a problem for mitochondrial replacement therapy (MRT). This is because the mitochondrial genome is placed in a novel nuclear environment using this technique. In contrast, it is inherited with half the mother’s genome during normal reproduction, a genome that it is relatively compatible with, since the mother is alive. Here, I review the evidence of whether mito-nuclear interactions are likely to pose a problem for MRT. The majority of the available experimental evidence, both in humans and other species, sugg...
Source: Genetics - March 30, 2017 Category: Genetics & Stem Cells Authors: Eyre-Walker, A. Tags: Review Source Type: research
The Evolving Definition of the Term "Gene" [Perspectives]
This paper presents a history of the changing meanings of the term "gene," over more than a century, and a discussion of why this word, so crucial to genetics, needs redefinition today. In this account, the first two phases of 20th century genetics are designated the "classical" and the "neoclassical" periods, and the current molecular-genetic era the "modern period." While the first two stages generated increasing clarity about the nature of the gene, the present period features complexity and confusion. Initially, the term "gene" was coined to denote an abstract "unit of inheritance," to which no specific material attrib...
Source: Genetics - March 30, 2017 Category: Genetics & Stem Cells Authors: Portin, P., Wilkins, A. Tags: Perspectives Source Type: research
ISSUE HIGHLIGHTS [Issue Highlights]
(Source: Genetics)
Source: Genetics - March 30, 2017 Category: Genetics & Stem Cells Tags: Issue Highlights Source Type: research
Inferring Recent Demography from Isolation by Distance of Long Shared Sequence Blocks [Population and Evolutionary Genetics]
Recently it has become feasible to detect long blocks of nearly identical sequence shared between pairs of genomes. These identity-by-descent (IBD) blocks are direct traces of recent coalescence events and, as such, contain ample signal to infer recent demography. Here, we examine sharing of such blocks in two-dimensional populations with local migration. Using a diffusion approximation to trace genetic ancestry, we derive analytical formulas for patterns of isolation by distance of IBD blocks, which can also incorporate recent population density changes. We introduce an inference scheme that uses a composite-likelihood ap...
Source: Genetics - March 6, 2017 Category: Genetics & Stem Cells Authors: Ringbauer, H., Coop, G., Barton, N. H. Tags: Population and Evolutionary Genetics Source Type: research
Inferring Individual Inbreeding and Demographic History from Segments of Identity by Descent in Ficedula Flycatcher Genome Sequences [Population and Evolutionary Genetics]
This study provides a rare genomic glimpse into demographic history and the mechanisms underlying the genome-wide distribution of ROH. (Source: Genetics)
Source: Genetics - March 6, 2017 Category: Genetics & Stem Cells Authors: Kardos, M., Qvarnstrom, A., Ellegren, H. Tags: Population and Evolutionary Genetics Source Type: research
Dynamics and Fate of Beneficial Mutations Under Lineage Contamination by Linked Deleterious Mutations [Population and Evolutionary Genetics]
Beneficial mutations drive adaptive evolution, yet their selective advantage does not ensure their fixation. Haldane’s application of single-type branching process theory showed that genetic drift alone could cause the extinction of newly arising beneficial mutations with high probability. With linkage, deleterious mutations will affect the dynamics of beneficial mutations and might further increase their extinction probability. Here, we model the lineage dynamics of a newly arising beneficial mutation as a multitype branching process. Our approach accounts for the combined effects of drift and the stochastic accumul...
Source: Genetics - March 6, 2017 Category: Genetics & Stem Cells Authors: Penisson, S., Singh, T., Sniegowski, P., Gerrish, P. Tags: Population and Evolutionary Genetics Source Type: research
The Relative Contributions of the X Chromosome and Autosomes to Local Adaptation [Population and Evolutionary Genetics]
Models of sex chromosome and autosome evolution yield key predictions about the genomic basis of adaptive divergence, and such models have been important in guiding empirical research in comparative genomics and studies of speciation. In addition to the adaptive differentiation that occurs between species over time, selection also favors genetic divergence across geographic space, with subpopulations of single species evolving conspicuous differences in traits involved in adaptation to local environmental conditions. The potential contribution of sex chromosomes (the X or Z) to local adaptation remains unclear, as we curre...
Source: Genetics - March 6, 2017 Category: Genetics & Stem Cells Authors: Lasne, C., Sgro, C. M., Connallon, T. Tags: Population and Evolutionary Genetics Source Type: research
Fluctuating Selection in the Moran [Population and Evolutionary Genetics]
Contrary to classical population genetics theory, experiments demonstrate that fluctuating selection can protect a haploid polymorphism in the absence of frequency dependent effects on fitness. Using forward simulations with the Moran model, we confirm our analytical results showing that a fluctuating selection regime, with a mean selection coefficient of zero, promotes polymorphism. We find that increases in heterozygosity over neutral expectations are especially pronounced when fluctuations are rapid, mutation is weak, the population size is large, and the variance in selection is big. Lowering the frequency of fluctuati...
Source: Genetics - March 6, 2017 Category: Genetics & Stem Cells Authors: Dean, A. M., Lehman, C., Yi, X. Tags: Population and Evolutionary Genetics Source Type: research
julius seizure, a Drosophila Mutant, Defines a Neuronal Population Underlying Epileptogenesis [Developmental and Behavioral Genetics]
Epilepsy is a neural disorder characterized by recurrent seizures. Bang-sensitive Drosophila represent an important model for studying epilepsy and neuronal excitability. Previous work identified the bang-sensitive gene slamdance (sda) as an allele of the aminopeptidase N gene. Here we show through extensive genetic analysis, including recombination frequency, deficiency mapping, transposon insertion complementation testing, RNA interference (RNAi), and genetic rescue that the gene responsible for the seizure sensitivity is julius seizure (jus), formerly CG14509, which encodes a novel transmembrane domain protein. We also ...
Source: Genetics - March 6, 2017 Category: Genetics & Stem Cells Authors: Horne, M., Krebushevski, K., Wells, A., Tunio, N., Jarvis, C., Francisco, G., Geiss, J., Recknagel, A., Deitcher, D. L. Tags: Developmental and Behavioral Genetics Source Type: research
The Lipocalin LPR-1 Cooperates with LIN-3/EGF Signaling To Maintain Narrow Tube Integrity in Caenorhabditis elegans [Developmental and Behavioral Genetics]
Lipocalins are secreted cup-shaped glycoproteins that bind sterols, fatty acids, and other lipophilic molecules. Lipocalins have been implicated in a wide array of processes related to lipophilic cargo transport, sequestration, and signaling, and several are used as biomarkers for human disease, but the functions of most lipocalins remain poorly understood. Here we show that the Caenorhabditis elegans lipocalin LPR-1 is required to maintain apical membrane integrity and a continuous lumen in two narrow unicellular tubes, the excretory duct and pore, during a period of rapid lumen elongation. LPR-1 fusion protein is express...
Source: Genetics - March 6, 2017 Category: Genetics & Stem Cells Authors: Pu, P., Stone, C. E., Burdick, J. T., Murray, J. I., Sundaram, M. V. Tags: Developmental and Behavioral Genetics Source Type: research
