scholarly journals Genetic Basis of Aerobically Supported Voluntary Exercise: Results from a Selection Experiment with House Mice

Genetics ◽  
2020 ◽  
Vol 216 (3) ◽  
pp. 781-804
Author(s):  
David A. Hillis ◽  
Liran Yadgary ◽  
George M. Weinstock ◽  
Fernando Pardo-Manuel de Villena ◽  
Daniel Pomp ◽  
...  
Keyword(s):  
Wheel Running ◽  
Allele Frequencies ◽  
Limb Bud ◽  
Exercise Behavior ◽  
Voluntary Exercise ◽  
Selection Experiment ◽  
Nucleotide Polymorphisms ◽  
Athletic Ability ◽  
Laboratory Rodents ◽  
Genomic Regions

The biological basis of exercise behavior is increasingly relevant for maintaining healthy lifestyles. Various quantitative genetic studies and selection experiments have conclusively demonstrated substantial heritability for exercise behavior in both humans and laboratory rodents. In the “High Runner” selection experiment, four replicate lines of Mus domesticus were bred for high voluntary wheel running (HR), along with four nonselected control (C) lines. After 61 generations, the genomes of 79 mice (9–10 from each line) were fully sequenced and single nucleotide polymorphisms (SNPs) were identified. We used nested ANOVA with MIVQUE estimation and other approaches to compare allele frequencies between the HR and C lines for both SNPs and haplotypes. Approximately 61 genomic regions, across all somatic chromosomes, showed evidence of differentiation; 12 of these regions were differentiated by all methods of analysis. Gene function was inferred largely using Panther gene ontology terms and KO phenotypes associated with genes of interest. Some of the differentiated genes are known to be associated with behavior/motivational systems and/or athletic ability, including Sorl1, Dach1, and Cdh10. Sorl1 is a sorting protein associated with cholinergic neuron morphology, vascular wound healing, and metabolism. Dach1 is associated with limb bud development and neural differentiation. Cdh10 is a calcium ion binding protein associated with phrenic neurons. Overall, these results indicate that selective breeding for high voluntary exercise has resulted in changes in allele frequencies for multiple genes associated with both motivation and ability for endurance exercise, providing candidate genes that may explain phenotypic changes observed in previous studies.

scholarly journals Enhanced genetic differentiation of Japanese chum salmon identified from a meta-analysis of allele frequencies

2019 ◽  
Author(s):  
Shuichi Kitada ◽  
Hirohisa Kishino
Keyword(s):  
Population Structure ◽  
Genetic Differentiation ◽  
Chum Salmon ◽  
Meta Analysis ◽  
Distribution Range ◽  
Allele Frequencies ◽  
Geographical Information ◽  
Data Sets ◽  
Nucleotide Polymorphisms ◽  
Athletic Ability

AbstractThe number of individuals returning to Japan, the location of the world’s largest chum salmon hatchery program, has declined substantially over two decades. To find the genetic cause of this severe decline never previously experienced, we analyzed published genetic data sets for adult chum salmon, namely, 10 microsatellites, 53 single nucleotide polymorphisms (SNPs) and a combined mitochondrial DNA locus (mtDNA3), and three isozymes, from 576 locations in the distribution range (n = 76,363). The SNPs were selected for stock identification to achieve high accuracy, were highly differentiated in the distribution range and included important genes related to reproduction, growth and immune responses. By contrasting the genetic differentiation of these genes with the population structure estimated from the neutral microsatellite markers, we identified genes that distort the neutral population structure. We matched the sampling locations of SNPs and isozymes with those of microsatellites based on geographical information, and performed regression analyses of SNP and isozyme allele frequencies of matched locations on the population structure. TreeMix analysis indicated two admixture events, from Japan/Korea to Russia and the Alaskan Peninsula. Meta-analysis of allele frequencies identified three outliers, mtDNA3 (control region and NADH-3), GnRH373 (gonadotropin-releasing hormone) and U502241 (unknown), which showed enhanced differentiation in Japanese/Korean populations compared with the others. GnRH improves stream odor discrimination and has increased expression in adult chum salmon brains during homing migration, suggesting that the current admixture was caused by GnRH373 differentiation. mtDNA plays a key role in endurance exercise training, energy metabolism and oxygen consumption, suggesting that the significant reduction in mtDNA3 allele frequencies reduced aerobic athletic ability, as observed in YouTube videos. Our analyses relied on limited data sets, though they were the best available. Clearly, genome-wide data will be needed to fully address this issue.

scholarly journals Genetic architecture of voluntary exercise in an advanced intercross line of mice

2010 ◽  
Vol 42 (2) ◽  
pp. 190-200 ◽  
Author(s):  
Scott A. Kelly ◽  
Derrick L. Nehrenberg ◽  
Jeremy L. Peirce ◽  
Kunjie Hua ◽  
Brian M. Steffy ◽  
...  
Keyword(s):  
Genetic Basis ◽  
Wheel Running ◽  
Voluntary Exercise ◽  
Maximum Speed ◽  
Voluntary Activity ◽  
Advanced Intercross Line ◽  
Time Period ◽  
The Mean ◽  
Genomic Regions ◽  
Insight Into

Exercise is essential for health, yet the amount, duration, and intensity that individuals engage in are strikingly variable, even under prescription. Our focus was to identify the locations and effects of quantitative trait loci (QTL) controlling genetic predisposition for exercise-related traits, utilizing a large advanced intercross line (AIL) of mice. This AIL (G4) population originated from a reciprocal cross between mice with genetic propensity for increased voluntary exercise [high-runner (HR) line, selectively bred for increased wheel running] and the inbred strain C57BL/6J. After adjusting for family structure, we detected 32 significant and 13 suggestive QTL representing both daily running traits (distance, duration, average speed, and maximum speed) and the mean of these traits on days 5 and 6 (the selection criteria for HR) of a 6-day test conducted at 8 wk of age, with many colocalizing to similar genomic regions. Additionally, seven significant and five suggestive QTL were observed for the slope and intercept of a linear regression across all 6 days of running, some representing a combination of the daily traits. We also observed two significant and two suggestive QTL for body mass before exercise. These results, from a well-defined animal model, reinforce a genetic basis for the predisposition to engage in voluntary exercise, dissect this predisposition into daily segments across a continuous time period, and present unique QTL that may provide insight into the initiation, continuation, and temporal pattern of voluntary activity in mammals.

scholarly journals Genome-wide association study in almost 195,000 individuals identifies 50 previously unidentified genetic loci for eye color

2021 ◽  
Vol 7 (11) ◽  
pp. eabd1239
Author(s):  
Mark Simcoe ◽  
Ana Valdes ◽  
Fan Liu ◽  
Nicholas A. Furlotte ◽  
David M. Evans ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Color Variation ◽  
Genome Wide Association ◽  
Nucleotide Polymorphisms ◽  
Melanin Pigmentation ◽  
Eye Color ◽  
Human Eye ◽  
Genome Wide ◽  
Genomic Regions

Human eye color is highly heritable, but its genetic architecture is not yet fully understood. We report the results of the largest genome-wide association study for eye color to date, involving up to 192,986 European participants from 10 populations. We identify 124 independent associations arising from 61 discrete genomic regions, including 50 previously unidentified. We find evidence for genes involved in melanin pigmentation, but we also find associations with genes involved in iris morphology and structure. Further analyses in 1636 Asian participants from two populations suggest that iris pigmentation variation in Asians is genetically similar to Europeans, albeit with smaller effect sizes. Our findings collectively explain 53.2% (95% confidence interval, 45.4 to 61.0%) of eye color variation using common single-nucleotide polymorphisms. Overall, our study outcomes demonstrate that the genetic complexity of human eye color considerably exceeds previous knowledge and expectations, highlighting eye color as a genetically highly complex human trait.

scholarly journals Voluntary exercise and cardiac remodeling in a myocardial infarction model

Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 545-555
Author(s):  
Hamad Al Shahi ◽  
Tomoyasu Kadoguchi ◽  
Kazunori Shimada ◽  
Kosuke Fukao ◽  
Satoshi Matsushita ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Cardiac Remodeling ◽  
Skeletal Muscles ◽  
Wheel Running ◽  
Voluntary Exercise ◽  
Fibroblast Growth Factor 21 ◽  
Expression Levels ◽  
Factor Α ◽  
Necrosis Factor

AbstractWe investigated the effects of voluntary exercise after myocardial infarction (MI) on cardiac function, remodeling, and inflammation. Male C57BL/6J mice were divided into the following four groups: sedentary + sham (Sed-Sh), sedentary + MI (Sed-MI), exercise + sham (Ex-Sh), and exercise + MI (Ex-MI). MI induction was performed by ligation of the left coronary artery. Exercise consisting of voluntary wheel running started after the operation and continued for 4 weeks. The Ex-MI mice had significantly increased cardiac function compared with the Sed-MI mice. The Ex-MI mice showed significantly reduced expression levels of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and IL-10 in the infarcted area of the left ventricle compared with the Sed-MI mice. In the Ex-MI mice, the expression levels of fibrosis-related genes including collagen I and III were decreased compared to the Sed-MI mice, and the expression levels of IL-1β, IL-6, follistatin-like 1, fibroblast growth factor 21, and mitochondrial function-related genes were significantly elevated in skeletal muscle compared with the Sed mice. The plasma levels of IL-6 were also significantly elevated in the Ex-MI group compared with the Sed-MI groups. These findings suggest that voluntary exercise after MI may improve in cardiac remodeling associated with anti-inflammatory effects in the myocardium and myokine production in the skeletal muscles.

scholarly journals Genetic Variants in Smoking-Related Genes in Two Smoking Cessation Programs: A Cross-Sectional Study

2021 ◽  
Vol 18 (12) ◽  
pp. 6597
Author(s):  
Gloria Pérez-Rubio ◽  
Luis Alberto López-Flores ◽  
Ana Paula Cupertino ◽  
Francisco Cartujano-Barrera ◽  
Luz Myriam Reynales-Shigematsu ◽  
...  
Keyword(s):  
Smoking Cessation ◽  
Cross Sectional Study ◽  
Nucleotide Polymorphisms ◽  
Sectional Study ◽  
Cross Sectional ◽  
Single Nucleotide ◽  
Genotype Frequencies ◽  
Quitting Smoking ◽  
Genes Encoding ◽  
Genomic Regions

Previous studies have identified variants in genes encoding proteins associated with the degree of addiction, smoking onset, and cessation. We aimed to describe thirty-one single nucleotide polymorphisms (SNPs) in seven candidate genomic regions spanning six genes associated with tobacco-smoking in a cross-sectional study from two different interventions for quitting smoking: (1) thirty-eight smokers were recruited via multimedia to participate in e-Decídete! program (e-Dec) and (2) ninety-four attended an institutional smoking cessation program on-site. SNPs genotyping was done by real-time PCR using TaqMan probes. The analysis of alleles and genotypes was carried out using the EpiInfo v7. on-site subjects had more years smoking and tobacco index than e-Dec smokers (p < 0.05, both); in CYP2A6 we found differences in the rs28399433 (p < 0.01), the e-Dec group had a higher frequency of TT genotype (0.78 vs. 0.35), and TG genotype frequency was higher in the on-site group (0.63 vs. 0.18), same as GG genotype (0.03 vs. 0.02). Moreover, three SNPs in NRXN1, two in CHRNA3, and two in CHRNA5 had differences in genotype frequencies (p < 0.01). Cigarettes per day were different (p < 0.05) in the metabolizer classification by CYP2A6 alleles. In conclusion, subjects attending a mobile smoking cessation intervention smoked fewer cigarettes per day, by fewer years, and by fewer cumulative pack-years. There were differences in the genotype frequencies of SNPs in genes related to nicotine metabolism and nicotine dependence. Slow metabolizers smoked more cigarettes per day than intermediate and normal metabolizers.

scholarly journals Allele frequencies of single nucleotide polymorphisms of clinically important drug-metabolizing enzymes CYP2C9, CYP2C19, and CYP3A4 in a Thai population

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rattanaporn Sukprasong ◽  
Sumonrat Chuwongwattana ◽  
Napatrupron Koomdee ◽  
Thawinee Jantararoungtong ◽  
Santirhat Prommas ◽  
...  
Keyword(s):  
Snp Genotyping ◽  
Allele Frequencies ◽  
Nucleotide Polymorphisms ◽  
Poor Metabolizer ◽  
Thai Population ◽  
Metabolizing Enzymes ◽  
Single Nucleotide ◽  
Genotyping Assay ◽  
Intermediate Metabolizer ◽  
Important Drug

AbstractPrior knowledge of allele frequencies of cytochrome P450 polymorphisms in a population is crucial for the revision and optimization of existing medication choices and doses. In the current study, the frequency of the CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*3, CYP2C19*6, CYP2C19*17, and CYP3A4 (rs4646437) alleles in a Thai population across different regions of Thailand was examined. Tests for polymorphisms of CYP2C9 and CYP3A4 were performed using TaqMan SNP genotyping assay and CYP2C19 was performed using two different methods; TaqMan SNP genotyping assay and Luminex x Tag V3. The blood samples were collected from 1205 unrelated healthy individuals across different regions within Thailand. Polymorphisms of CYP2C9 and CYP2C19 were transformed into phenotypes, which included normal metabolizer (NM), intermediate metabolizer (IM), poor metabolizer (PM), and rapid metabolizers (RM). The CYP2C9 allele frequencies among the Thai population were 0.08% and 5.27% for the CYP2C9*2 and CYP2C9*3 alleles, respectively. The CYP2C19 allele frequencies among the Thai population were 25.60%, 2.50%, 0.10%, and 1.80% for the CYP2C19*2, CYP2C19*3, CYP2C19*6, and CYP2C19*17 alleles, respectively. The allele frequency of the CYP3A4 (rs4646437) variant allele was 28.50% in the Thai population. The frequency of the CYP2C9*3 allele was significantly lower among the Northern Thai population (P < 0.001). The frequency of the CYP2C19*17 allele was significantly higher in the Southern Thai population (P < 0.001). Our results may provide an understanding of the ethnic differences in drug responses and support for the utilization of pharmacogenomics testing in clinical practice.

scholarly journals Parent-of-origin effects on voluntary exercise levels and body composition in mice

2010 ◽  
Vol 40 (2) ◽  
pp. 111-120 ◽  
Author(s):  
Scott A. Kelly ◽  
Derrick L. Nehrenberg ◽  
Kunjie Hua ◽  
Ryan R. Gordon ◽  
Theodore Garland ◽  
...  
Keyword(s):  
Body Composition ◽  
Body Fat ◽  
Wheel Running ◽  
Voluntary Exercise ◽  
Phenotypic Variance ◽  
In Utero Environment ◽  
Dependent Activity ◽  
Health Related ◽  
Parent Of Origin ◽  
Origin Effects

Despite the health-related benefits of exercise, many people do not engage in enough activity to realize the rewards, and little is known regarding the genetic or environmental components that account for this individual variation. We created and phenotyped a large G4 advanced intercross line originating from reciprocal crosses between mice with genetic propensity for increased voluntary exercise (HR line) and the inbred strain C57BL/6J. G4 females (compared to males) ran significantly more when provided access to a running wheel and were smaller with a greater percentage of body fat pre- and postwheel access. Change in body composition resulting from a 6-day exposure to wheels varied between the sexes with females generally regulating energy balance more precisely in the presence of exercise. We observed parent-of-origin effects on most voluntary wheel running and body composition traits, which accounted for 3–13% of the total phenotypic variance pooled across sexes. G4 individuals descended from progenitor (F0) crosses of HR♀ and C57BL/6J♂ ran greater distances, spent more time running, ran at higher maximum speeds/day, and had lower percent body fat and higher percent lean mass than mice descended from reciprocal progenitor crosses (C57BL/6J♀ × HR♂). For some traits, significant interactions between parent of origin and sex were observed. We discuss these results in the context of sex dependent activity and weight loss patterns, the contribution of parent-of-origin effects to predisposition for voluntary exercise, and the genetic (i.e., X-linked or mtDNA variations), epigenetic (i.e., genomic imprinting), and environmental (i.e., in utero environment or maternal care) phenomena potentially modulating these effects.

scholarly journals A NOTE ON PHASING LONG GENOMIC REGIONS USING LOCAL HAPLOTYPE PREDICTIONS

2006 ◽  
Vol 04 (03) ◽  
pp. 639-647 ◽  
Author(s):  
ELEAZAR ESKIN ◽  
RODED SHARAN ◽  
ERAN HALPERIN
Keyword(s):  
Large Scale ◽  
Computational Cost ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Novel Approach ◽  
Maximum Likelihood Criterion ◽  
The Common ◽  
Genomic Regions ◽  
High Computational Cost ◽  
Combining Information

The common approaches for haplotype inference from genotype data are targeted toward phasing short genomic regions. Longer regions are often tackled in a heuristic manner, due to the high computational cost. Here, we describe a novel approach for phasing genotypes over long regions, which is based on combining information from local predictions on short, overlapping regions. The phasing is done in a way, which maximizes a natural maximum likelihood criterion. Among other things, this criterion takes into account the physical length between neighboring single nucleotide polymorphisms. The approach is very efficient and is applied to several large scale datasets and is shown to be successful in two recent benchmarking studies (Zaitlen et al., in press; Marchini et al., in preparation). Our method is publicly available via a webserver at .

Beneficial effects of voluntary wheel running on the properties of dystrophic mouse muscle

1996 ◽  
Vol 80 (2) ◽  
pp. 670-679 ◽  
Author(s):  
A. Hayes ◽  
D. A. Williams
Keyword(s):  
Skeletal Muscles ◽  
Wheel Running ◽  
Voluntary Exercise ◽  
Mdx Mice ◽  
Free Access ◽  
Type I ◽  
Fiber Types ◽  
Force Output ◽  
Mouse Muscle ◽  
Beneficial Effects

Effects of voluntary exercise on the isometric contractile, fatigue, and histochemical properties of hindlimb dystrophic (mdx and 129ReJ dy/dy) skeletal muscles were investigated. Mice were allowed free access to a voluntary running wheel at 4 wk of age for a duration of 16 (mdx) or 5 (dy/dy) wk. Running performance of mdx mice (approximately 4 km/day at 1.6 km/h) was inferior to normal mice (approximately 6.5 km/day at 2.1 km/h). However, exercise improved the force output (approximately 15%) and the fatigue resistance of both C57BL/10 and mdx soleus muscles. These changes coincided with increased proportions of smaller type I fibers and decreased proportions of larger type IIa fibers in the mdx soleus. The extensor digitorum longus of mdx, but not of normal, mice also exhibited improved resistance to fatigue and conversion towards oxidative fiber types. The dy/dy animals were capable of exercising, yet ran significantly less than normal animals (approximately 0.5 km/day). Despite this, running increased the force output of the plantaris muscle (approximately 50%). Taken together, the results showed that exercise can have beneficial effects on dystrophic skeletal muscles.

scholarly journals Allele frequency divergence reveals ubiquitous influence of positive selection in Drosophila

2021 ◽  
Author(s):  
Jason Bertram
Keyword(s):  
Allele Frequency ◽  
Evolutionary Biology ◽  
Polymorphic Locus ◽  
Purifying Selection ◽  
Allele Frequencies ◽  
Intermediate Allele ◽  
Genome Wide ◽  
Signature Of Selection ◽  
Basic Objective ◽  
Genomic Regions

Resolving the role of natural selection is a basic objective of evolutionary biology. It is generally difficult to detect the influence of selection because ubiquitous non-selective stochastic change in allele frequencies (genetic drift) degrades evidence of selection. As a result, selection scans typically only identify genomic regions that have undergone episodes of intense selection. Yet it seems likely such episodes are the exception; the norm is more likely to involve subtle, concurrent selective changes at a large number of loci. We develop a new theoretical approach that uncovers a previously undocumented genome-wide signature of selection in the collective divergence of allele frequencies over time. Applying our approach to temporally-resolved allele frequency measurements from laboratory and wild Drosophila populations, we quantify the selective contribution to allele frequency divergence and find that selection has substantial effects on much of the genome. We further quantify the magnitude of the total selection coefficient (a measure of the combined effects of direct and linked selection) at a typical polymorphic locus, and find this to be large (of order 1%) even though most mutations are not directly under selection. We find that selective allele frequency divergence is substantial at intermediate allele frequencies, which we argue is most parsimoniously explained by positive --- not purifying --- selection. Thus, in these populations most mutations are far from evolving neutrally in the short term (tens of generations), including mutations with neutral fitness effects, and the result cannot be explained simply as a purging of deleterious mutations.

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