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165 results for “Genetic mutation”

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dryad28/100

Data from: Genetic regulatory network motifs constrain adaptation through curvature in the landscape of mutational (co)variance

Systems biology is accumulating a wealth of understanding about the structure of genetic regulatory networks, leading to a more complete picture of the complex genotype-phenotype relationship. However, models of multivariate phenotypic evolution based on quantitative genetics have largely not incorporated a network-based view of genetic variation. Here we model a set of two-node, two-phenotype genetic network motifs, covering a full range of regulatory interactions. We find that network interactions result in different patterns of mutational (co)variance at the phenotypic level (the M-matrix), not only across network motifs but also across phenotypic space within single motifs. This effect is due almost entirely to mutational input of additive genetic (co)variance. Variation in M has the effect of stretching and bending phenotypic space with respect to evolvability, analogous to the curvature of space-time under general relativity, and similar mathematical tools may apply in each case. We explored the consequences of curvature in mutational variation by simulating adaptation under divergent selection with gene flow. Both standing genetic variation (the G-matrix) and rate of adaptation are constrained by M, so that G and adaptive trajectories are curved across phenotypic space. Under weak selection the phenotypic mean at migration-selection balance also depends on M.

opencc-zeroDec 2012View details →

dryad28/100

Data from: The conditional nature of genetic interactions: the consequences of wild-type backgrounds on mutational interactions in a genome-wide modifier screen

The phenotypic outcome of a mutation cannot be simply mapped onto the underlying DNA variant. Instead, the phenotype is a function of the allele, the genetic background in which it occurs and the environment where the mutational effects are expressed. While the influence of genetic background on the expressivity of individual mutations is recognized, its consequences on the interactions between genes, or the genetic network they form, is largely unknown. The description of genetic networks is essential for much of biology; yet if, and how, the topologies of such networks are influenced by background is unknown. Furthermore, a comprehensive examination of the background dependent nature of genetic interactions may lead to identification of novel modifiers of biological processes. Previous work in Drosophila melanogaster demonstrated that wild-type genetic background influences the effects of an allele of scalloped (sd), with respect to both its principal consequence on wing development and its interactions with a mutation in optomotor blind. In this study we address whether the background dependence of mutational interactions is a general property of genetic systems by performing a genome wide dominant modifier screen of the sdE3 allele in two wild-type genetic backgrounds using molecularly defined deletions. We demonstrate that ~74% of all modifiers of the sdE3 phenotype are background-dependent due in part to differential sensitivity to genetic perturbation. These background dependent interactions include some with qualitative differences in the phenotypic outcome, as well as instances of sign epistasis. This suggests that genetic interactions are often contingent on genetic background, with flexibility in genetic networks due to segregating variation in populations. Such background dependent effects can substantially alter conclusions about how genes influence biological processes, the potential for genetic screens in alternative wild-type backgrounds identifying new loci that contribute to trait expression, and the inferences of the topology of genetic networks.

opencc-zeroDec 2012View details →

dryad28/100

Data from: The genetics of adaptation to discrete heterogeneous environments: frequent mutation or large-effect alleles can allow range expansion

Range expansions are complex evolutionary and ecological processes. From an evolutionary standpoint, a populations' adaptive capacity can determine the success or failure of expansion. Using individual-based simulations, we model range expansion over a two-dimensional, approximately continuous landscape. We investigate the ability of populations to adapt across patchy environmental gradients and examine how the effect sizes of mutations influence the ability to adapt to novel environments during range expansion. We find that genetic architecture and landscape patchiness both have the ability to change the outcome of adaptation and expansion over the landscape. Adaptation to new environments succeeds via many mutations of small effect or few of large effect, but not via the intermediate between these cases. Higher genetic variance contributes to increased ability to adapt, but an alternative route of successful adaptation can proceed from low genetic variance scenarios with alleles of sufficiently large effect. Steeper environmental gradients can prevent adaptation and range expansion on both linear and patchy landscapes. When the landscape is partitioned into local patches with sharp changes in phenotypic optimum, the local magnitude of change between subsequent patches in the environment determines the success of adaptation to new patches during expansion.

opencc-zeroDec 2015View details →

ClinicalTrials.gov28/100

Targeted Therapy in Treating Patients With Incurable Non-Small Cell Lung Cancer With Genetic Mutations

ClinicalTrials.gov study NCT02949843. IPD Sharing: Not stated. Countries: 1. Publications: 0.

restrictedIPD-UNDECIDEDFeb 2026View details →

ClinicalTrials.gov28/100

Study of Muscle Abnormalities in Patients With Specific Genetic Mutations

ClinicalTrials.gov study NCT00001871. IPD Sharing: Not stated. Countries: 1. Publications: 3.

restrictedIPD-UNDECIDEDFeb 2026View details →

ClinicalTrials.gov28/100

An Intervention to Increase Genetic Testing in Families Who May Share a Gene Mutation Related to Cancer Risk and An Intervention to Help Patients and Their Primary Care Providers Stay Up-to-date About

ClinicalTrials.gov study NCT05420064. IPD Sharing: YES. Countries: 1. Publications: 0.

controlledIPD-YESFeb 2026View details →

dryad28/100