scholarly journals Natural selection drives genome-wide evolution via chance genetic associations

2021 ◽  
Author(s):  
Zachariah Gompert ◽  
Jeffrey Feder ◽  
Patrik Nosil
Keyword(s):  
Natural Selection ◽  
Field Experiments ◽  
Indirect Selection ◽  
Direct Selection ◽  
Deer Mice ◽  
Major Theme ◽  
Genetic Associations ◽  
Genome Wide ◽  
Stick Insects ◽  
Causal Variants

Abstract Understanding selection's impact on the genome is a major theme in biology. Functionally-neutral genetic regions can be affected indirectly by natural selection, via their statistical association with genes under direct selection. The genomic extent of such indirect selection, particularly across loci not physically linked to those under direct selection, remains poorly understood, as does the time scale at which indirect selection occurs. Here we use field experiments and genomic data to show that widespread statistical associations with genes known to affect fitness in stick insects, deer mice and stickleback fish cause many genetic loci across the genome to be impacted indirectly by selection. We then show that statistical associations with other, unknown causal variants make aspects of evolution more predictable in stick insects. Thus, natural selection combines with chance genetic associations to affect genome-wide evolution across linked and unlinked loci and even in modest-sized populations.

scholarly journals Functional Annotation of Putative Regulatory Elements at Cancer Susceptibility Loci

2014 ◽  
Vol 13s2 ◽  
pp. CIN.S13789
Author(s):  
Stephanie A. Rosse ◽  
Paul L. Auer ◽  
Christopher S. Carlson
Keyword(s):  
Cancer Susceptibility ◽  
Association Studies ◽  
Regulatory Elements ◽  
Genome Wide Association Studies ◽  
Genetic Associations ◽  
Functional Polymorphisms ◽  
Functional Variants ◽  
Genome Wide ◽  
Regulatory Variant ◽  
Causal Variants

Most cancer-associated genetic variants identified from genome-wide association studies (GWAS) do not obviously change protein structure, leading to the hypothesis that the associations are attributable to regulatory polymorphisms. Translating genetic associations into mechanistic insights can be facilitated by knowledge of the causal regulatory variant (or variants) responsible for the statistical signal. Experimental validation of candidate functional variants is onerous, making bioinformatic approaches necessary to prioritize candidates for laboratory analysis. Thus, a systematic approach for recognizing functional (and, therefore, likely causal) variants in noncoding regions is an important step toward interpreting cancer risk loci. This review provides a detailed introduction to current regulatory variant annotations, followed by an overview of how to leverage these resources to prioritize candidate functional polymorphisms in regulatory regions.

The future of research with carnivorous plants

2018 ◽  
Author(s):  
Aaron M. Ellison ◽  
Lubomír Adamec
Keyword(s):  
Natural Selection ◽  
Population Biology ◽  
Field Experiments ◽  
Evolutionary Dynamics ◽  
Species Concept ◽  
Intraspecific Variability ◽  
Carnivorous Plants ◽  
Assisted Migration ◽  
Transcriptomic Data ◽  
Phylogenetic Framework

The material presented in the chapters of Carnivorous Plants: Physiology, Ecology, and Evolution together provide a suite of common themes that could provide a framework for increasing progress in understanding carnivorous plants. All speciose genera would benefit from more robust, intra-generic classifications in a phylogenetic framework that uses a unified species concept. As more genomic, proteomic, and transcriptomic data accrue, new insights will emerge regarding trap biochemistry and regulation; interactions with commensals; and the importance of intraspecific variability on which natural selection works. Continued elaboration of field experiments will provide new insights into basic physiology; population biology; plant-animal and plant-microbe relationships; and evolutionary dynamics, all of which will aid conservation efforts and contribute to discussions of assisted migration as the climate continues to change.

scholarly journals Protogyny in Autumn Migration: Do Male Birds ”Play Chicken”?

The Auk ◽  
2005 ◽  
Vol 122 (1) ◽  
pp. 71-81 ◽  
Author(s):  
Alexander M. Mills
Keyword(s):  
Migratory Birds ◽  
Indirect Selection ◽  
Male Competition ◽  
Autumn Migration ◽  
Direct Selection ◽  
Differential Migration ◽  
The North ◽  
Parsimonious Explanation ◽  
Ground Conditions ◽  
Wintering Ground

AbstractProtandry, the earlier arrival of males than of females on breeding areas, occurs in many taxa, including many migratory birds. Numerous hypotheses have been generated to explain protandry. Using bird-banding records, I show that protogyny, the earlier migration of females, frequently occurs in the autumn, though it is less universal and less dramatic than spring protandry. In one species, it occurs in both hatch-year and adult birds. When (1) spring and autumn, (2) departures and arrivals, and (3) breeding and wintering ground conditions are considered, hypotheses generated only to explain spring protandry can be more thoroughly evaluated. Using that approach, the most parsimonious explanation of differential migration between the sexes explains earlier male arrival in spring and later male departure in autumn through either (1) indirect selection operating on intrasexual male competition for territories or (2) direct selection operating on intersexual relations requiring males to be present on breeding territories when females are present. In autumn-protogynous species, males may ”play chicken,” balancing the benefits of remaining longer than females and protecting territories for subsequent years against the costs of remaining in the north under deteriorating conditions and delaying the acquisition of a good winter territory.Protogynie et migration automnale: Est-ce que les mâles ”jouent les dégonflés”?

scholarly journals Genome-Wide Analysis of Sex Disparities in the Genetic Architecture of Lung and Colorectal Cancers

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 686
Author(s):  
Alireza Nazarian ◽  
Alexander M. Kulminski
Keyword(s):  
Nucleotide Polymorphisms ◽  
Genetic Associations ◽  
Significance Level ◽  
Association Analyses ◽  
Complex Disorders ◽  
Specific Effects ◽  
Genome Wide ◽  
Genetic Mechanisms ◽  
Sex Disparities ◽  
Almost All

Almost all complex disorders have manifested epidemiological and clinical sex disparities which might partially arise from sex-specific genetic mechanisms. Addressing such differences can be important from a precision medicine perspective which aims to make medical interventions more personalized and effective. We investigated sex-specific genetic associations with colorectal (CRCa) and lung (LCa) cancers using genome-wide single-nucleotide polymorphisms (SNPs) data from three independent datasets. The genome-wide association analyses revealed that 33 SNPs were associated with CRCa/LCa at P < 5.0 × 10−6 neither males or females. Of these, 26 SNPs had sex-specific effects as their effect sizes were statistically different between the two sexes at a Bonferroni-adjusted significance level of 0.0015. None had proxy SNPs within their ±1 Mb regions and the closest genes to 32 SNPs were not previously associated with the corresponding cancers. The pathway enrichment analyses demonstrated the associations of 35 pathways with CRCa or LCa which were mostly implicated in immune system responses, cell cycle, and chromosome stability. The significant pathways were mostly enriched in either males or females. Our findings provided novel insights into the potential sex-specific genetic heterogeneity of CRCa and LCa at SNP and pathway levels.

scholarly journals Editing GWAS: experimental approaches to dissect and exploit disease-associated genetic variation

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Shuquan Rao ◽  
Yao Yao ◽  
Daniel E. Bauer
Keyword(s):  
Genome Editing ◽  
Genetic Variants ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Functional Studies ◽  
Functional Genetics ◽  
Genome Wide ◽  
Causal Variants ◽  
Experimental Approaches

AbstractGenome-wide association studies (GWAS) have uncovered thousands of genetic variants that influence risk for human diseases and traits. Yet understanding the mechanisms by which these genetic variants, mainly noncoding, have an impact on associated diseases and traits remains a significant hurdle. In this review, we discuss emerging experimental approaches that are being applied for functional studies of causal variants and translational advances from GWAS findings to disease prevention and treatment. We highlight the use of genome editing technologies in GWAS functional studies to modify genomic sequences, with proof-of-principle examples. We discuss the challenges in interrogating causal variants, points for consideration in experimental design and interpretation of GWAS locus mechanisms, and the potential for novel therapeutic opportunities. With the accumulation of knowledge of functional genetics, therapeutic genome editing based on GWAS discoveries will become increasingly feasible.

scholarly journals Genome-wide association analysis of metabolic syndrome quantitative traits in the GENNID multiethnic family study

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Jia Y. Wan ◽  
Deborah L. Goodman ◽  
Emileigh L. Willems ◽  
Alexis R. Freedland ◽  
Trina M. Norden-Krichmar ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Family Study ◽  
Genome Wide Association ◽  
European American ◽  
Japanese American ◽  
Genetic Associations ◽  
Chromosome 11 ◽  
Genome Wide ◽  
American Families

Abstract Background To identify genetic associations of quantitative metabolic syndrome (MetS) traits and characterize heterogeneity across ethnic groups. Methods Data was collected from GENetics of Noninsulin dependent Diabetes Mellitus (GENNID), a multiethnic resource of Type 2 diabetic families and included 1520 subjects in 259 African-American, European-American, Japanese-Americans, and Mexican-American families. We focused on eight MetS traits: weight, waist circumference, systolic and diastolic blood pressure, high-density lipoprotein, triglycerides, fasting glucose, and insulin. Using genotyped and imputed data from Illumina’s Multiethnic array, we conducted genome-wide association analyses with linear mixed models for all ethnicities, except for the smaller Japanese-American group, where we used additive genetic models with gene-dropping. Results Findings included ethnic-specific genetic associations and heterogeneity across ethnicities. Most significant associations were outside our candidate linkage regions and were coincident within a gene or intergenic region, with two exceptions in European-American families: (a) within previously identified linkage region on chromosome 2, two significant GLI2-TFCP2L1 associations with weight, and (b) one chromosome 11 variant near CADM1-LINC00900 with pleiotropic blood pressure effects. Conclusions This multiethnic family study found genetic heterogeneity and coincident associations (with one case of pleiotropy), highlighting the importance of including diverse populations in genetic research and illustrating the complex genetic architecture underlying MetS.

scholarly journals Genome-wide fine-mapping identifies pleiotropic and functional variants that predict many traits across global cattle populations

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ruidong Xiang ◽  
Iona M. MacLeod ◽  
Hans D. Daetwyler ◽  
Gerben de Jong ◽  
Erin O’Connor ◽  
...  
Keyword(s):  
Dairy Cattle ◽  
Chromosome Segment ◽  
Multiple Traits ◽  
Functional Variants ◽  
Genome Wide ◽  
The Usa ◽  
Pleiotropic Qtl ◽  
Causal Variants ◽  
Genetic Value ◽  
Bayesian Mixture Models

AbstractThe difficulty in finding causative mutations has hampered their use in genomic prediction. Here, we present a methodology to fine-map potentially causal variants genome-wide by integrating the functional, evolutionary and pleiotropic information of variants using GWAS, variant clustering and Bayesian mixture models. Our analysis of 17 million sequence variants in 44,000+ Australian dairy cattle for 34 traits suggests, on average, one pleiotropic QTL existing in each 50 kb chromosome-segment. We selected a set of 80k variants representing potentially causal variants within each chromosome segment to develop a bovine XT-50K genotyping array. The custom array contains many pleiotropic variants with biological functions, including splicing QTLs and variants at conserved sites across 100 vertebrate species. This biology-informed custom array outperformed the standard array in predicting genetic value of multiple traits across populations in independent datasets of 90,000+ dairy cattle from the USA, Australia and New Zealand.

scholarly journals Age by Single Nucleotide Polymorphism Interactions on Bronchodilator Response in Asthmatics

2021 ◽  
Vol 11 (1) ◽  
pp. 59
Author(s):  
Kirsten Voorhies ◽  
Joanne E. Sordillo ◽  
Michael McGeachie ◽  
Elizabeth Ampleford ◽  
Alberta L. Wang ◽  
...  
Keyword(s):  
Candidate Genes ◽  
P Value ◽  
Genome Wide Association Studies ◽  
Genetic Associations ◽  
Single Nucleotide ◽  
Significance Level ◽  
Bronchodilator Response ◽  
Genome Wide ◽  
A Genome ◽  
Β2 Agonists

An unaddressed and important issue is the role age plays in modulating response to short acting β2-agonists in individuals with asthma. The objective of this study was to identify whether age modifies genetic associations of single nucleotide polymorphisms (SNPs) with bronchodilator response (BDR) to β2-agonists. Using three cohorts with a total of 892 subjects, we ran a genome wide interaction study (GWIS) for each cohort to examine SNP by age interactions with BDR. A fixed effect meta-analysis was used to combine the results. In order to determine if previously identified BDR SNPs had an age interaction, we also examined 16 polymorphisms in candidate genes from two published genome wide association studies (GWAS) of BDR. There were no significant SNP by age interactions on BDR using the genome wide significance level of 5 × 10−8. Using a suggestive significance level of 5 × 10−6, three interactions, including one for a SNP within PRAG1 (rs4840337), were significant and replicated at the significance level of 0.05. Considering candidate genes from two previous GWAS of BDR, three SNPs (rs10476900 (near ADRB2) [p-value = 0.009], rs10827492 (CREM) [p-value = 0.02], and rs72646209 (NCOA3) [p-value = 0.02]) had a marginally significant interaction with age on BDR (p < 0.05). Our results suggest age may be an important modifier of genetic associations for BDR in asthma.

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