scholarly journals Substitutions are boring: some arguments about parallel mutations and repetitive DNA

2018 ◽  
Author(s):  
Maximilian Oliver Press ◽  
Ashley Hall ◽  
Elizabeth Morton ◽  
Christine Queitsch
Keyword(s):  
Dna Sequences ◽  
Copy Number ◽  
Large Scale ◽  
Association Studies ◽  
Evolutionary Genetics ◽  
Common Features ◽  
Genomic Technologies ◽  
Fisher Model ◽  
The Common ◽  
Parallel Mutation

Extant genomes are largely shaped by the global transposition, copy number fluctuation, and rearrangement of DNA sequences, rather than by the substitutions of single nucleotides. Although many of these large-scale mutations have low probabilities and are unlikely to repeat, others are recurrent or predictable in their effects, leading to stereotyped genome architectures and genetic variation in both eukaryotes and prokaryotes. Such recurrent, parallel mutation modes can profoundly shape the paths taken by evolution, and directly undermine the Wright-Fisher model of evolutionary genetics. Similar patterns are also evident at the smaller scales of individual genes or short genomic sequences. The scale and extent of this ‘non-substitution’ variation has only recently come into focus through the advent of new genomic technologies; however, it still not widely included in genotype-phenotype association studies. In this review, we identify the common features of these disparate mutational phenomena and comment on the importance and interpretation of these mutational patterns.

scholarly journals CNest: A Novel Copy Number Association Discovery Method Uncovers 862 New Associations from 200,629 Whole Exome Sequence Datasets in the UK Biobank

2021 ◽  
Author(s):  
Tomas W Fitzgerald ◽  
Ewan Birney
Keyword(s):  
Copy Number ◽  
Large Scale ◽  
Association Studies ◽  
Genomic Variation ◽  
Next Generation Sequencing Data ◽  
Genome Wide Association Studies ◽  
Uk Biobank ◽  
Genome Wide ◽  
The Uk ◽  
Ngs Data

Copy number variation (CNV) has long been known to influence human traits having a rich history of research into common and rare genetic disease and although CNV is accepted as an important class of genomic variation, progress on copy number (CN) phenotype associations from Next Generation Sequencing data (NGS) has been limited, in part, due to the relative difficulty in CNV detection and an enrichment for large numbers of false positives. To date most successful CN genome wide association studies (CN-GWAS) have focused on using predictive measures of dosage intolerance or gene burden tests to gain sufficient power for detecting CN effects. Here we present a novel method for large scale CN analysis from NGS data generating robust CN estimates and allowing CN-GWAS to be performed genome wide in discovery mode. We provide a detailed analysis in the large scale UK BioBank resource and a specifically designed software package for deriving CN estimates from NGS data that are robust enough to be used for CN-GWAS. We use these methods to perform genome wide CN-GWAS analysis across 78 human traits discovering 862 genetic associations that are likely to contribute strongly to trait distributions based solely on their CN or by acting in concert with other genetic variation. Finally, we undertake an analysis comparing CNV and SNP association signals across the same traits and samples, defining specific CNV association classes based on whether they could be detected using standard SNP-GWAS in the UK Biobank.

scholarly journals Bayesian copy number detection and association in large-scale studies

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Stephen Cristiano ◽  
David McKean ◽  
Jacob Carey ◽  
Paige Bracci ◽  
Paul Brennan ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Copy Number ◽  
Large Scale ◽  
Association Studies ◽  
Regulatory Elements ◽  
Bayesian Regression ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Batch Effects ◽  
Genome Wide

Abstract Background Germline copy number variants (CNVs) increase risk for many diseases, yet detection of CNVs and quantifying their contribution to disease risk in large-scale studies is challenging due to biological and technical sources of heterogeneity that vary across the genome within and between samples. Methods We developed an approach called CNPBayes to identify latent batch effects in genome-wide association studies involving copy number, to provide probabilistic estimates of integer copy number across the estimated batches, and to fully integrate the copy number uncertainty in the association model for disease. Results Applying a hidden Markov model (HMM) to identify CNVs in a large multi-site Pancreatic Cancer Case Control study (PanC4) of 7598 participants, we found CNV inference was highly sensitive to technical noise that varied appreciably among participants. Applying CNPBayes to this dataset, we found that the major sources of technical variation were linked to sample processing by the centralized laboratory and not the individual study sites. Modeling the latent batch effects at each CNV region hierarchically, we developed probabilistic estimates of copy number that were directly incorporated in a Bayesian regression model for pancreatic cancer risk. Candidate associations aided by this approach include deletions of 8q24 near regulatory elements of the tumor oncogene MYC and of Tumor Suppressor Candidate 3 (TUSC3). Conclusions Laboratory effects may not account for the major sources of technical variation in genome-wide association studies. This study provides a robust Bayesian inferential framework for identifying latent batch effects, estimating copy number, and evaluating the role of copy number in heritable diseases.

Which insect species and why?

2021 ◽  
pp. 8-16
Author(s):  
Hanna Bjone ◽  
Elaine C. Fitches
Keyword(s):  
Large Scale ◽  
Animal Feed ◽  
Insect Species ◽  
Industrial Scale ◽  
Potential Candidate ◽  
Common Features ◽  
Feed Production ◽  
Candidate Species ◽  
The Common

Abstract This chapter describes the common features determining the suitability of insects for small- and industrial-scale farming, the main insect species currently being produced on a large scale for feed production and other potential candidate species. Natural consumption of insects by animals and which insects are suitable for which animal feed is also briefly discussed.

The labours and golden apples of maritime history: Large-scale national and international research projects in Greece

2020 ◽  
Vol 32 (2) ◽  
pp. 444-450
Author(s):  
Katerina Galani
Keyword(s):  
International Research ◽  
Large Scale ◽  
Human Interaction ◽  
Maritime History ◽  
Research Projects ◽  
Common Features ◽  
The Common ◽  
Golden Apples

Over the last decades, maritime history has evolved into one of the most dynamic, self-standing disciplines among Greek historical studies. The production of books and papers that probe the multilevel human interaction with the sea has been prolific, while Greek maritime historians exhibit an ever-growing presence in the international fora. This paper argues that the roots of this unprecedented boom lie in a series of large-scale research projects funded both by international and national agencies. It underlines the common features of these schemes that formulated a methodology, or rather a ‘school’ of maritime history, and introduces to a wider audience the most significant projects that are currently underway.

0306 Exploring the feasibility of using copy number variants as genetic markers through large-scale whole genome sequencing experiments

2016 ◽  
Vol 94 (suppl_5) ◽  
pp. 146-146
Author(s):  
D. M. Bickhart ◽  
L. Xu ◽  
J. L. Hutchison ◽  
J. B. Cole ◽  
D. J. Null ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genetic Markers ◽  
Genome Sequencing ◽  
Copy Number ◽  
Large Scale ◽  
Copy Number Variants ◽  
Whole Genome

Migraine: Genetic Variants and Clinical Phenotypes

2019 ◽  
Vol 26 (34) ◽  
pp. 6207-6221 ◽  
Author(s):  
Innocenzo Rainero ◽  
Alessandro Vacca ◽  
Flora Govone ◽  
Annalisa Gai ◽  
Lorenzo Pinessi ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Association Studies ◽  
Mthfr Gene ◽  
Genome Wide Association Studies ◽  
Clinical Phenotypes ◽  
Network Analyses ◽  
Genome Wide ◽  
Genomic Studies ◽  
The Common ◽  
The Relationship

Migraine is a common, chronic neurovascular disorder caused by a complex interaction between genetic and environmental risk factors. In the last two decades, molecular genetics of migraine have been intensively investigated. In a few cases, migraine is transmitted as a monogenic disorder, and the disease phenotype cosegregates with mutations in different genes like CACNA1A, ATP1A2, SCN1A, KCNK18, and NOTCH3. In the common forms of migraine, candidate genes as well as genome-wide association studies have shown that a large number of genetic variants may increase the risk of developing migraine. At present, few studies investigated the genotype-phenotype correlation in patients with migraine. The purpose of this review was to discuss recent studies investigating the relationship between different genetic variants and the clinical characteristics of migraine. Analysis of genotype-phenotype correlations in migraineurs is complicated by several confounding factors and, to date, only polymorphisms of the MTHFR gene have been shown to have an effect on migraine phenotype. Additional genomic studies and network analyses are needed to clarify the complex pathways underlying migraine and its clinical phenotypes.

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