Role of Overlapping Generations in Maintaining Genetic Variation in a Fluctuating Environment

A Niemann–Pick C1-like-1 egy szterolfelismerő domént tartalmazó membránfehérje, amelyet nagy számban expresszálnak csúcsi felszínükön a bélhámsejtek. Az utóbbi évek vizsgálatai azt igazolták, hogy ez a fehérje szükséges a szabad koleszterin bejutásához a bélhámsejtekbe a bél lumenéből. Biokémiai vizsgálatok azt igazolták, hogy a Niemann–Pick C1-like-1-hez kötődik az ezetimib, amely egy hatékony koleszterinfelszívódást gátló szer. A bélből történő koleszterinfelszívódás ütemében és az ezetimibkezelés hatékonyságában tapasztalt egyéni eltérések hátterében felmerült néhány Niemann–Pick C1-like-1 génvariáció oki szerepe.

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Variation in the morphology and flowering time of cluster clover (Trifolium glomeratum L.) and its relationship to distribution in southern Australia

Australian Journal of Agricultural Research ◽

10.1071/ar9951027 ◽

1995 ◽

Vol 46 (5) ◽

pp. 1027 ◽

Cited By ~ 14

Author(s):

FP Smith ◽

PS Cocks ◽

MA Ewing

Keyword(s):

Genetic Variation ◽

Flowering Time ◽

Seed Mass ◽

Annual Rainfall ◽

Strongly Correlated ◽

Summer Maximum ◽

Maximum Temperatures ◽

Pattern Of Variation ◽

Growth Habits

Cluster clover is a widely distributed and ecologically successful introduced legume in southern Australia. In an attempt to understand the role of genetic variation in this success, morphological and physiological traits were measured in 94 accessions from southern Australia and 6 from the Mediterranean basin. Flowering time ranged from 105 to 185 days after sowing, but was not strongly correlated with annual rainfall or length of growing season at the site of collection. Variation in other traits partitioned the populations into two morphs which, apart from flowering time and leaf marker, were largely homogeneous. The morphs differed significantly in floret number per inflorescence (22 v. 32-37) and seed mass (379 8g v. 523 8g), had different growth habits and strong within-morph associations between leaf markers and stipule and petal coloration. The morphs differed in their distributions within southern Australia and the pattern of distribution was related to summer maximum temperatures, winter minimum temperatures and spring rainfall. These results demonstrate that genetic variation has been important to the success of cluster clover and suggests that the variation is organized. The pattern of variation observed and its relationship to ecogeography is consistent with findings for other highly inbreeding species. A map of the species distribution in Western Australia is presented.

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The Role of Genetic Variation in Thiopurine Methyltransferase Activity and Efficacy and/or Side Effects of Azathioprine Therapy in Dermatologic Patients

Archives of Dermatology ◽

10.1001/archderm.1995.01690210119023 ◽

1995 ◽

Vol 131 (9) ◽

pp. 1087 ◽

Cited By ~ 1

Author(s):

Alexander Anstey

Keyword(s):

Genetic Variation ◽

Side Effects ◽

Thiopurine Methyltransferase ◽

Methyltransferase Activity ◽

Azathioprine Therapy

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Genetic Variation of Serotonin Function and Cognitive Control

Journal of Cognitive Neuroscience ◽

10.1162/jocn.2007.19.12.1923 ◽

2007 ◽

Vol 19 (12) ◽

pp. 1923-1931 ◽

Cited By ~ 55

Author(s):

Alexander Strobel ◽

Gesine Dreisbach ◽

Johannes Müller ◽

Thomas Goschke ◽

Burkhard Brocke ◽

...

Keyword(s):

Genetic Variation ◽

Cognitive Control ◽

Personality Traits ◽

Anxiety And Depression ◽

Continuous Performance ◽

Continuous Performance Task ◽

Performance Task ◽

The Impact ◽

Related Personality

Although it is widely accepted that serotonin plays a pivotal role in the modulation of anxiety- and depression-related personality traits as well as in the pathogenesis of anxiety disorders and depression, the role of serotonin in cognition is less clear. In the present study, we investigated the involvement of serotonin in cognitive behaviors by examining the impact of genetic variation in key regulators of serotonergic neurotransmission on behavioral measures in a cognitive control task. Eighty-five healthy participants performed a cued continuous performance task (the AX Continuous Performance Task [AXCPT]) and were genotyped for polymorphisms in the transcriptional control regions of the tryptophan hydroxylase 2 gene (TPH2 G-703T; rs4570625) and the serotonin transporter gene (5-HTTLPR). The core result was that individuals lacking the rare TPH2 T allele were not faster than T allele carriers, but committed fewer errors and were less variable in responding. These findings parallel those of a recent study where an enhancement of executive control in individuals without the rare TPH2 T/T genotype was observed. Together with recent evidence that individuals without the T allele exhibit higher scores in anxiety- and depression-related personality traits, our results underscore the role of the TPH2 G-703T polymorphism in the modulation of behavior and raise the intriguing possibility that genetic variants associated with higher negative emotionality may have beneficial effects on some cognitive functions.

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Genetic resistance of Eucalyptus globulus to autumn gum moth defoliation and the role of cuticular waxes

Canadian Journal of Forest Research ◽

10.1139/x02-118 ◽

2002 ◽

Vol 32 (11) ◽

pp. 1961-1969 ◽

Cited By ~ 39

Author(s):

T H Jones ◽

B M Potts ◽

R E Vaillancourt ◽

N W Davies

Keyword(s):

Genetic Variation ◽

Eucalyptus Globulus ◽

Field Trial ◽

Genetic Resistance ◽

Cuticular Wax ◽

Wax Esters ◽

Broad Sense ◽

Broad Sense Heritability ◽

Cuticular Waxes

This study investigated the association between resistance of Eucalyptus globulus Labill. to autumn gum moth (Mnesempala privata Guenée) defoliation and cuticular wax compounds. In a field trial consisting of clonally replicated F2 families of E. globulus, situated in Tasmania, Australia, significant genetic variation in resistance was detected in two of three F2 families. The broad-sense heritability for defoliation within families ranged from 0.24 to 0.33. The 15 most resistant and the 15 most susceptible genotypes within each variable family were compared for their relative levels of 26 cuticular wax compounds. While no significant correlation between resistance and total wax yield estimates was found, significant differences were detected between resistant and susceptible classes in the relative quantities of several aliphatic phenylethyl and benzyl wax esters within both families. This association does not appear to be a response induced by defoliation. The broad-sense heritabilities of the variation in these compounds were high (0.820.94). Our findings suggest that these wax compounds are a mechanism of genetic resistance to autumn gum moth in E. globulus.

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Collaborative Cross Founder Expression Analysis (CCFEA)

10.1101/2021.03.04.422591 ◽

2021 ◽

Author(s):

Richard R Green ◽

Renee C Ireton ◽

Martin Ferris ◽

Kathleen Muenzen ◽

David R Crosslin ◽

...

Keyword(s):

Gene Expression ◽

Genetic Variation ◽

Gene Expression Data ◽

Viral Infections ◽

Collaborative Cross ◽

Visualization Tool ◽

Expression Data ◽

Individual Gene ◽

Rnaseq Data

To understand the role of genetic variation in SARS and Influenza infections we developed CCFEA, a shiny visualization tool using public RNAseq data from the collaborative cross (CC) founder strains (A/J, C57BL/6J, 129s1/SvImJ, NOD/ShILtJ, NZO/HILtJ, CAST/EiJ, PWK/PhJ, and WSB/EiJ). Individual gene expression data is displayed across founders, viral infections and days post infection.

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Investigation of the genetic variation in ACE2 on the structural recognition by the novel coronavirus (SARS-CoV-2)

10.21203/rs.3.rs-29037/v2 ◽

2020 ◽

Author(s):

Xingyi Guo ◽

Zhishan Chen ◽

Yumin Xia ◽

Weiqiang Lin ◽

Hongzhi Li

Keyword(s):

Genetic Variation ◽

The Novel ◽

S Protein ◽

Angiotensin Converting Enzyme 2 ◽

Missense Variants ◽

Catalytic Metal ◽

Using Data ◽

Novel Coronavirus ◽

Insight Into

Abstract Background: The outbreak of coronavirus disease (COVID-19) was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), through its surface spike glycoprotein (S-protein) recognition on the receptor Angiotensin-converting enzyme 2 (ACE2) in humans. However, it remains unclear how genetic variations in ACE2 may affect its function and structure, and consequently alter the recognition by SARS-CoV-2. Methods: We have systemically characterized missense variants in the gene ACE2 using data from the Genome Aggregation Database (gnomAD; N = 141,456). To investigate the putative deleterious role of missense variants, six existing functional prediction tools were applied to evaluate their impact. We further analyzed the structural flexibility of ACE2 and its protein-protein interface with the S-protein of SARS-CoV-2 using our developed Legion Interfaces Analysis (LiAn) program.Results: Here, we characterized a total of 12 ACE2 putative deleterious missense variants. Of those 12 variants, we further showed that p.His378Arg could directly weaken the binding of catalytic metal atom to decrease ACE2 activity and p.Ser19Pro could distort the most important helix to the S-protein. Another seven missense variants may affect secondary structures (i.e. p.Gly211Arg; p.Asp206Gly; p.Arg219Cys; p.Arg219His, p.Lys341Arg, p.Ile468Val, and p.Ser547Cys), whereas p.Ile468Val with AF = 0.01 is only present in Asian.Conclusions: We provide strong evidence of putative deleterious missense variants in ACE2 that are present in specific populations, which could disrupt the function and structure of ACE2. These findings provide novel insight into the genetic variation in ACE2 which may affect the SARS-CoV-2 recognition and infection, and COVID-19 susceptibility and treatment.

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APOC3 genetic variation, serum triglycerides, and risk of coronary artery disease in Asian Indians, Europeans, and other ethnic groups

Lipids in Health and Disease ◽

10.1186/s12944-021-01531-8 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Shiwali Goyal ◽

Yosuke Tanigawa ◽

Weihua Zhang ◽

Jin-Fang Chai ◽

Marcio Almeida ◽

...

Keyword(s):

Coronary Artery Disease ◽

Genetic Variation ◽

Coronary Artery ◽

American Indians ◽

Asian Indians ◽

Small Subset ◽

Serum Triglycerides ◽

Artery Disease ◽

Cad Risk

Abstract Background Hypertriglyceridemia has emerged as a critical coronary artery disease (CAD) risk factor. Rare loss-of-function (LoF) variants in apolipoprotein C-III have been reported to reduce triglycerides (TG) and are cardioprotective in American Indians and Europeans. However, there is a lack of data in other Europeans and non-Europeans. Also, whether genetically increased plasma TG due to ApoC-III is causally associated with increased CAD risk is still unclear and inconsistent. The objectives of this study were to verify the cardioprotective role of earlier reported six LoF variants of APOC3 in South Asians and other multi-ethnic cohorts and to evaluate the causal association of TG raising common variants for increasing CAD risk. Methods We performed gene-centric and Mendelian randomization analyses and evaluated the role of genetic variation encompassing APOC3 for affecting circulating TG and the risk for developing CAD. Results One rare LoF variant (rs138326449) with a 37% reduction in TG was associated with lowered risk for CAD in Europeans (p = 0.007), but we could not confirm this association in Asian Indians (p = 0.641). Our data could not validate the cardioprotective role of other five LoF variants analysed. A common variant rs5128 in the APOC3 was strongly associated with elevated TG levels showing a p-value 2.8 × 10− 424. Measures of plasma ApoC-III in a small subset of Sikhs revealed a 37% increase in ApoC-III concentrations among homozygous mutant carriers than the wild-type carriers of rs5128. A genetically instrumented per 1SD increment of plasma TG level of 15 mg/dL would cause a mild increase (3%) in the risk for CAD (p = 0.042). Conclusions Our results highlight the challenges of inclusion of rare variant information in clinical risk assessment and the generalizability of implementation of ApoC-III inhibition for treating atherosclerotic disease. More studies would be needed to confirm whether genetically raised TG and ApoC-III concentrations would increase CAD risk.

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The crucial role of genome-wide genetic variation in conservation

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2104642118 ◽

2021 ◽

Vol 118 (48) ◽

pp. e2104642118

Author(s):

Marty Kardos ◽

Ellie E. Armstrong ◽

Sarah W. Fitzpatrick ◽

Samantha Hauser ◽

Philip W. Hedrick ◽

...

Keyword(s):

Genetic Variation ◽

Environmental Changes ◽

Population Viability ◽

Adaptive Potential ◽

Biodiversity Crisis ◽

Genome Wide ◽

Simulation Based ◽

Functional Genetic Variation

The unprecedented rate of extinction calls for efficient use of genetics to help conserve biodiversity. Several recent genomic and simulation-based studies have argued that the field of conservation biology has placed too much focus on conserving genome-wide genetic variation, and that the field should instead focus on managing the subset of functional genetic variation that is thought to affect fitness. Here, we critically evaluate the feasibility and likely benefits of this approach in conservation. We find that population genetics theory and empirical results show that conserving genome-wide genetic variation is generally the best approach to prevent inbreeding depression and loss of adaptive potential from driving populations toward extinction. Focusing conservation efforts on presumably functional genetic variation will only be feasible occasionally, often misleading, and counterproductive when prioritized over genome-wide genetic variation. Given the increasing rate of habitat loss and other environmental changes, failure to recognize the detrimental effects of lost genome-wide genetic variation on long-term population viability will only worsen the biodiversity crisis.

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