scholarly journals Analysis of genetic variation contributing to measured speed in Thoroughbreds identifies genomic regions involved in the transcriptional response to exercise

2019 ◽  
Vol 50 (6) ◽  
pp. 670-685 ◽  
Author(s):  
G. Farries ◽  
K. F. Gough ◽  
A. C. Parnell ◽  
B. A. McGivney ◽  
C. L. McGivney ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Transcriptional Response ◽  
Measured Speed ◽  
Genomic Regions ◽  
Response To Exercise

scholarly journals Genetic variation in recombination rate in the pig

2021 ◽  
Vol 53 (1) ◽  
Author(s):  
Martin Johnsson ◽  
Andrew Whalen ◽  
Roger Ros-Freixedes ◽  
Gregor Gorjanc ◽  
Ching-Yi Chen ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Recombination Rate ◽  
Large Scale ◽  
Genome Wide Association Study ◽  
Genetic Material ◽  
A Genome ◽  
Pig Genome ◽  
Genetic Length ◽  
Trait Locus ◽  
Genomic Regions

Abstract Background Meiotic recombination results in the exchange of genetic material between homologous chromosomes. Recombination rate varies between different parts of the genome, between individuals, and is influenced by genetics. In this paper, we assessed the genetic variation in recombination rate along the genome and between individuals in the pig using multilocus iterative peeling on 150,000 individuals across nine genotyped pedigrees. We used these data to estimate the heritability of recombination and perform a genome-wide association study of recombination in the pig. Results Our results confirmed known features of the recombination landscape of the pig genome, including differences in genetic length of chromosomes and marked sex differences. The recombination landscape was repeatable between lines, but at the same time, there were differences in average autosome-wide recombination rate between lines. The heritability of autosome-wide recombination rate was low but not zero (on average 0.07 for females and 0.05 for males). We found six genomic regions that are associated with recombination rate, among which five harbour known candidate genes involved in recombination: RNF212, SHOC1, SYCP2, MSH4 and HFM1. Conclusions Our results on the variation in recombination rate in the pig genome agree with those reported for other vertebrates, with a low but nonzero heritability, and the identification of a major quantitative trait locus for recombination rate that is homologous to that detected in several other species. This work also highlights the utility of using large-scale livestock data to understand biological processes.

scholarly journals The dynamic effect of regulatory genetic variation on the in vivo ER stress transcriptional response

2021 ◽  
Author(s):  
Nikki D. Russell ◽  
Clement Y. Chow
Keyword(s):  
Genetic Variation ◽  
Stress Response ◽  
Er Stress ◽  
Transcriptional Response ◽  
Mouse Strains ◽  
Transcriptional Responses ◽  
Er Stress Response ◽  
Multiple Environments ◽  
Context Specific

AbstractGenotype x Environment (GxE) interactions occur when environmental conditions drastically change the effect of a genetic variant. In order to truly understand the effect of genetic variation, we need to incorporate multiple environments into our analyses. Many variants, under steady state conditions, may be silent or even have the opposite effect under stress conditions. This study uses an in vivo mouse model to investigate how the effect of genetic variation changes with tissue type and cellular stress. Endoplasmic reticulum (ER) stress occurs when misfolded proteins accumulate in the ER. This triggers the unfolded protein response (UPR), a large transcriptional response which attempts to return the cell to homeostasis. This transcriptional response, despite being a well conserved, basic cellular process, is highly variable across different genetic backgrounds, making it an ideal system to study GxE effects. In this study, we sought to better understand how genetic variation alters expression across tissues, in the presence and absence of ER stress. The use of different mouse strains and their F1s allow us to also identify context specific cis- and trans-regulatory mechanisms underlying variable transcriptional responses. We found hundreds of genes that respond to ER stress in a tissue- and/or genotype-dependent manner. Genotype-dependent ER stress-responsive genes are enriched for processes such as protein folding, apoptosis, and protein transport, indicating that some of the variability occurs in canonical ER stress factors. The majority of regulatory mechanisms underlying these variable transcriptional responses derive from cis-regulatory variation and are unique to a given tissue or ER stress state. This study demonstrates the need for incorporating multiple environments in future studies to better elucidate the effect of any particular genetic factor in basic biological pathways, like the ER stress response.Author SummaryThe effect of genetic variation is dependent on environmental context. Here we use genetically diverse mouse strains to understand how genetic variation interacts with stress state to produce variable transcriptional profiles. In this study, we take advantage of the endoplasmic reticulum (ER) stress response which is a large transcriptional response to misfolded proteins. Using this system, we uncovered tissue- and ER stress-specific effects of genetic variation on gene expression. Genes with genotype-dependent variable expression levels in response to ER stress were enriched for canonical ER stress functions, such as protein folding and transport. These variable effects of genetic variation are driven by unique sets of regulatory variation that are only active under context-specific circumstances. The results of this study highlight the importance of including multiple environments and genetic backgrounds when studying the ER stress response and other cellular pathways.

Analyzing the Effects of Genetic Variation in Noncoding Genomic Regions

2018 ◽  
pp. 119-144 ◽  
Author(s):  
Yasmina A. Mansur ◽  
Elena Rojano ◽  
Juan A.G. Ranea ◽  
James R. Perkins
Keyword(s):  
Genetic Variation ◽  
Genomic Regions

scholarly journals Genetic Variation and Mood Response to Exercise in the TIGER Study (OR08-08-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Graham Salmun ◽  
Molly Bray
Keyword(s):  
Heart Rate ◽  
Genetic Variation ◽  
Mood State ◽  
Kidney Diseases ◽  
Exercise Session ◽  
Specific Gene ◽  
Drd2 Gene ◽  
Minor Alleles ◽  
Major Allele ◽  
Response To Exercise

Abstract Objectives Our primary objective is to determine how mood response to exercise is influenced by genetic variation, controlling for exercise quantity and quality. Methods The Training Interventions and Genetics of Exercise Response (TIGER) Study is a prospective cohort study, in which sedentary subjects (18–35y, <30 min/wk for 30d prior to enrollment) participated in a 15-week program, exercising within a prescribed (65–85% maximum heart rate reserve) target heart rate zone for 3 d/wk. Before and after each exercise session, a subset of subjects (n = 247) completed a 10 cm visual analog scale (VAS: 0–100) for four mood states: fatigue, tension, depression, and hunger. Multiple linear regression was performed to examine the association between variation in DRD2, BDNF, and FTO genes and change in mood state following exercise, controlling for gender, exercise duration, and intensity. Results Exercise was associated on average with reduced feelings of fatigue (−3.18 ± 16.37), tension (−3.85 ± 12.97), and depression (−5.12 ± 8.20), and increased feelings of hunger (6.06 ± 10.54). Carriers of the major allele (A) in rs1362570 for the FTO gene experienced greater reductions in tension following exercise (AA or AG: −5.19 ± 1.08 vs GG: −1.16 ± 1.24, P < 0.02, respectively). Homozygotes for the major allele (A) in rs1799978 for the DRD2 gene displayed reduced feelings of tension in response to exercise, while those with one or more minor alleles reported increased tension (AA: −4.69 ± 0.89 vs AG or GG: + 2.25 ± 2.16, P < 0.005). Homozygotes for the major alleles in rs151948, rs1362570, and rs1799978 (for BDNF, FTO, & DRD2 genes, respectively) served as strong predictors for changes in feelings of tension following exercise, controlling for gender and exercise parameters (P < 0.001). Subjects with one or more minor alleles (A) in rs1800498 for DRD2 gene displayed greater increases in hunger in response to exercise (AA or AG: 7.17 ± 0.85 vs GG: 3.96 ± 1.09, P < 0.03). Conclusions Specific gene polymorphisms, exercise intensity, duration, and gender may influence, in part, the variable mood response to exercise. Funding Sources Funding for this research was provided by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health Grant.

scholarly journals Genetic Variation of Citrus Tristeza VirusIsolates from California and Spain: Evidence for Mixed Infections and Recombination

2001 ◽  
Vol 75 (17) ◽  
pp. 8054-8062 ◽  
Author(s):  
Luis Rubio ◽  
Marı́a Angeles Ayllón ◽  
Ping Kong ◽  
Andres Fernández ◽  
MaryLou Polek ◽  
...  
Keyword(s):  
Population Structure ◽  
Genetic Variation ◽  
Citrus Tristeza Virus ◽  
Geographic Origin ◽  
Mixed Infections ◽  
Sequence Variants ◽  
Genomic Regions ◽  
Tristeza Virus ◽  
Major Sequence ◽  
Citrus Tristeza

ABSTRACT We examined the population structure and genetic variation of four genomic regions within and between 30 Citrus tristeza virus (CTV) isolates from Spain and California. Our analyses showed that most isolates contained a population of sequence variants, with one being predominant. Four isolates showed two major sequence variants in some genomic regions. The two major variants of three of these isolates showed very low nucleotide identity to each other but were very similar to those of other isolates, suggesting the possibility of mixed infections with two divergent isolates. Incongruencies of phylogenetic relationships in the different genomic regions and statistical analyses suggested that the genomes of some CTV sequence variants originated by recombination events between diverged sequence variants. No correlation was observed between geographic origin and nucleotide distance, and thus from a genetic view, the Spanish and Californian isolates analyzed here could be considered members of the same population.

scholarly journals Genetic population structure constrains local adaptation in sticklebacks

2020 ◽  
Author(s):  
Petri Kemppainen ◽  
Zitong Li ◽  
Pasi Rastas ◽  
Ari Löytynoja ◽  
Bohao Fang ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Isolation By Distance ◽  
Regulatory Element ◽  
Morphological Data ◽  
Genetic Isolation ◽  
Genetic Population ◽  
Population Structuring ◽  
Different Populations ◽  
Trait Locus ◽  
Genomic Regions

AbstractRepeated and independent adaptation to specific environmental conditions from standing genetic variation is common. However, if genetic variation is limited, the evolution of similar locally adapted traits may be restricted to genetically different and potentially less optimal solutions, or prevented from happening altogether. Using a quantitative trait locus (QTL) mapping approach, we identified the genomic regions responsible for the repeated pelvic reduction (PR) in three crosses between nine-spined stickleback populations expressing full and reduced pelvic structures. In one cross, PR mapped to linkage group 7 (LG7) containing the gene Pitx1, known to control pelvic reduction also in the three-spined stickleback. In the two other crosses, PR was polygenic and attributed to ten novel QTL, of which 90% were unique to specific crosses. When screening the genomes from 27 different populations for deletions in the Pitx1 regulatory element, these were only found in the population in which PR mapped to LG7, even though the morphological data indicated large effect QTL for PR in several other populations as well. Consistent with the available theory and simulations parameterised on empirical data, we hypothesise that the observed variability in genetic architecture of PR is due to heterogeneity in the spatial distribution of standing genetic variation caused by strong population structuring and genetic isolation by distance in the sea.

scholarly journals Sites of active gene regulation in the prenatal frontal cortex and their role in neuropsychiatric disorders

2021 ◽  
Author(s):  
Manuela R. Kouakou ◽  
Darren Cameron ◽  
Eilis Hannon ◽  
Emma L. Dempster ◽  
Jonathan Mill ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Major Depressive Disorder ◽  
Genetic Variation ◽  
Frontal Cortex ◽  
Fetal Brain ◽  
Neuropsychiatric Disorders ◽  
Open Chromatin ◽  
Major Depressive ◽  
Genomic Regions ◽  
Neuropsychiatric Conditions

Common genetic variation appears to largely influence risk for neuropsychiatric disorders through effects on gene regulation. It is therefore possible to shed light on the biology of these conditions by testing for enrichment of associated genetic variation within regulatory genomic regions operating in specific tissues or cell types. Here, we have used ATAC-Seq to map open chromatin (an index of active regulatory genomic regions) in bulk tissue, NeuN+ and NeuN- nuclei from the prenatal human frontal cortex, and tested enrichment of SNP heritability for 5 neuropsychiatric disorders (autism spectrum disorder, ADHD, bipolar disorder, major depressive disorder and schizophrenia) within these regions. We observed significant enrichment of SNP heritability for ADHD, major depressive disorder and schizophrenia within open chromatin regions mapped in bulk fetal frontal cortex, and for all 5 tested neuropsychiatric conditions when we restricted these sites to those overlapping histone modifications indicative of enhancers (H3K4me1) or promoters (H3K4me3) in fetal brain. SNP heritability for neuropsychiatric disorders was significantly enriched in open chromatin regions identified in fetal frontal cortex NeuN- as well as NeuN+ nuclei overlapping fetal brain H3K4me1 or H3K4me3 sites. We additionally demonstrate the utility of our mapped open chromatin regions for prioritizing potentially functional SNPs at genome-wide significant risk loci for neuropsychiatric disorders. Our data provide evidence for an early neurodevelopmental component to a range of neuropsychiatric conditions and highlight an important role for regulatory genomic regions active within both NeuN+ and NeuN- cells of the prenatal brain.

scholarly journals FANCD2 tunes the UPR preventing mitochondrial stress-­induced common fragile site instability

2019 ◽  
Author(s):  
Philippe Fernandes ◽  
Benoit Miotto ◽  
Claude Saint-Ruf ◽  
Viola Nähse ◽  
Silvia Ravera ◽  
...  
Keyword(s):  
Gene Expression ◽  
Genome Instability ◽  
Fragile Site ◽  
Transcriptional Response ◽  
Genomic Analysis ◽  
Fragile Sites ◽  
The Unfolded Protein Response ◽  
And Function ◽  
Large Genes ◽  
Genomic Regions

AbstractCommon fragile sites (CFSs) are genomic regions frequently involved in cancer-associated rearrangements. Most CFSs lie within large genes, and their instability relies on transcription- and replication-dependent mechanisms. Here, we uncover a role for the UBL5-dependent branch of the unfolded protein response pathway (UPR) in the maintenance of CFS stability. We show that genetic or pharmacological UPR activation induces CFS gene expression and concomitant relocalization of FANCD2, a master regulator of CFS stability, to CFSs. Furthermore, a genomic analysis of FANCD2 binding sites identified an enrichment for mitochondrial UPR transcriptional response elements in FANCD2 bound regions. We demonstrated that depletion of FANCD2 increases CFS gene transcription and their instability while also inducing mitochondrial dysfunction and triggering the activation of the UPR pathway. Depletion of UBL5, a mediator of the UPR, but not ATF4, reduces CFS gene expression and breakage in FANCD2-depleted cells. We thus demonstrate that FANCD2 recruitment and function at CFSs depends on transcription and UPR signaling, and in absence of transcription or UBL5, FANCD2 is dispensable for CFS stability. We propose that FANCD2 coordinates nuclear and mitochondrial activities by tuning the UPR to prevent genome instability.

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