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1.
BMC Bioinformatics ; 21(1): 491, 2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33129253

RESUMO

BACKGROUND: Advances in genotyping and phenotyping techniques have enabled the acquisition of a great amount of data. Consequently, there is an interest in multivariate statistical analyses that identify genomic regions likely to contain causal mutations affecting multiple traits (i.e., pleiotropy). As the demand for multivariate analyses increases, it is imperative that optimal tools are available to assess their performance. To facilitate the testing and validation of these multivariate approaches, we developed simplePHENOTYPES, an R/CRAN package that simulates pleiotropy, partial pleiotropy, and spurious pleiotropy in a wide range of genetic architectures, including additive, dominance and epistatic models. RESULTS: We illustrate simplePHENOTYPES' ability to simulate thousands of phenotypes in less than one minute. We then provide two vignettes illustrating how to simulate sets of correlated traits in simplePHENOTYPES. Finally, we demonstrate the use of results from simplePHENOTYPES in a standard GWAS software, as well as the equivalence of simulated phenotypes from simplePHENOTYPES and other packages with similar capabilities. CONCLUSIONS: simplePHENOTYPES is a R/CRAN package that makes it possible to simulate multiple traits controlled by loci with varying degrees of pleiotropy. Its ability to interface with both commonly-used marker data formats and downstream quantitative genetics software and packages should facilitate a rigorous assessment of both existing and emerging statistical GWAS and GS approaches. simplePHENOTYPES is also available at https://github.com/samuelbfernandes/simplePHENOTYPES .


Assuntos
Simulação por Computador , Epistasia Genética , Ligação Genética , Pleiotropia Genética , Software , Frequência do Gene/genética , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Desequilíbrio de Ligação/genética , Análise Multivariada , Fenótipo , Característica Quantitativa Herdável , Fluxo de Trabalho
2.
Anim Sci J ; 91(1): e13467, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33043536

RESUMO

The objective of this study was to estimate genetic parameters for first calving reproductive traits and growth curve characteristics in Japanese Black cattle. The Gompertz growth function was fitted to body weight-age data to obtain the mature weight (MWT) and rate of maturing (ROM) of cows. Data of reproductive traits including the first service conception rate (CR) for heifers, age at the first calving (AFC), and gestation length for the first calving were collected. Records of 3,204 animals were used for analysis. Genetic parameters were estimated using a linear uni- and bivariate animal model. The heritability estimates were moderate (0.29 for ROM) and high (0.57 for MWT) for growth curve parameters and low (0.03-0.11) for reproductive traits. There was a negative genetic correlation between MWT and ROM (-0.26), suggesting that an animal with a faster ROM would show a lower MWT. CR was negatively correlated with MWT (-0.42) but significantly and positively correlated with ROM (0.91). There was a negative genetic correlation between AFC and MWT (-0.49). These results suggest that a heifer with a faster ROM and lower MWT would show a higher CR. Meanwhile, a heifer with a lower MWT would show a higher AFC.


Assuntos
Bovinos/crescimento & desenvolvimento , Bovinos/genética , Bovinos/fisiologia , Estudos de Associação Genética/veterinária , Característica Quantitativa Herdável , Reprodução/genética , Animais , Feminino , Fertilização/genética , Gravidez/genética
3.
Nat Commun ; 11(1): 4954, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-33009396

RESUMO

Genetic variation is of crucial importance for crop improvement. Landraces are valuable sources of diversity, but for quantitative traits efficient strategies for their targeted utilization are lacking. Here, we map haplotype-trait associations at high resolution in ~1000 doubled-haploid lines derived from three maize landraces to make their native diversity for early development traits accessible for elite germplasm improvement. A comparative genomic analysis of the discovered haplotypes in the landrace-derived lines and a panel of 65 breeding lines, both genotyped with 600k SNPs, points to untapped beneficial variation for target traits in the landraces. The superior phenotypic performance of lines carrying favorable landrace haplotypes as compared to breeding lines with alternative haplotypes confirms these findings. Stability of haplotype effects across populations and environments as well as their limited effects on undesired traits indicate that our strategy has high potential for harnessing beneficial haplotype variation for quantitative traits from genetic resources.


Assuntos
Haplótipos/genética , Característica Quantitativa Herdável , Zea mays/genética , Biblioteca Gênica , Variação Genética , Genoma de Planta , Estudo de Associação Genômica Ampla , Haploidia , Melhoramento Vegetal , Análise de Componente Principal , Zea mays/crescimento & desenvolvimento
4.
Anim Sci J ; 91(1): e13450, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32881233

RESUMO

Mycoplasma pneumonia of swine (MPS) is caused by Mycoplasma hyopneumoniae (M.hp) and is a common chronic respiratory disease of pigs. Recently, a genetically selected variant of the Landrace pig (Miyagino L2) has a lower incidence of pulmonary MPS lesions. We investigated the pathological and immunological characteristics of MPS resistance in these pigs (n = 24) by comparing with the normal landrace pig (control: n = 24). The pathological MPS lung lesion score in MPS-selected landrace pigs was significantly lower than in the control. The gene expression of interleukin (IL)-12p40, which acts as a chemoattractant and a component of the bioactive cytokines IL-12 and IL-23, was significantly higher at the hilar lymph nodes, lung, and spleen in MPS-selected landrace pigs than in control landrace pigs, and these were negatively correlated with the macroscopic MPS lung lesion score. In summary, we demonstrate that resistance against MPS in Miyagino L2 pigs is associated with IL-12p40 up-regulation, in comparison with normal landrace pigs without the MPS vaccine. In addition, a comparative study of macroscopic MPS lung lesions and IL-12p40 gene expression in lung and hilar lymph nodes may lead to beneficial selection traits for the genetic selection for MPS resistance in pigs.


Assuntos
Subunidade p40 da Interleucina-12/genética , Subunidade p40 da Interleucina-12/metabolismo , Pulmão/imunologia , Linfonodos/imunologia , Pneumonia Suína Micoplasmática/genética , Pneumonia Suína Micoplasmática/imunologia , Suínos/genética , Suínos/imunologia , Animais , Expressão Gênica , Predisposição Genética para Doença , Masculino , Característica Quantitativa Herdável , Seleção Genética , Regulação para Cima/genética
5.
Proc Natl Acad Sci U S A ; 117(36): 22323-22330, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32848059

RESUMO

Distinguishing which traits have evolved under natural selection, as opposed to neutral evolution, is a major goal of evolutionary biology. Several tests have been proposed to accomplish this, but these either rely on false assumptions or suffer from low power. Here, I introduce an approach to detecting selection that makes minimal assumptions and only requires phenotypic data from ∼10 individuals. The test compares the phenotypic difference between two populations to what would be expected by chance under neutral evolution, which can be estimated from the phenotypic distribution of an F2 cross between those populations. Simulations show that the test is robust to variation in the number of loci affecting the trait, the distribution of locus effect sizes, heritability, dominance, and epistasis. Comparing its performance to the QTL sign test-an existing test of selection that requires both genotype and phenotype data-the new test achieves comparable power with 50- to 100-fold fewer individuals (and no genotype data). Applying the test to empirical data spanning over a century shows strong directional selection in many crops, as well as on naturally selected traits such as head shape in Hawaiian Drosophila and skin color in humans. Applied to gene expression data, the test reveals that the strength of stabilizing selection acting on mRNA levels in a species is strongly associated with that species' effective population size. In sum, this test is applicable to phenotypic data from almost any genetic cross, allowing selection to be detected more easily and powerfully than previously possible.


Assuntos
Cruzamentos Genéticos , Modelos Genéticos , Seleção Genética/genética , Animais , Produtos Agrícolas/genética , Drosophila/anatomia & histologia , Drosophila/genética , Evolução Molecular , Variação Genética/genética , Humanos , Fenótipo , Locos de Características Quantitativas/genética , Característica Quantitativa Herdável , Saccharomyces cerevisiae/genética , Pigmentação da Pele/genética
6.
Am J Trop Med Hyg ; 103(3): 976-985, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32748773

RESUMO

Gene drive technologies represent powerful tools to develop vector control strategies that will complement the current approaches to mitigate arthropod-borne infectious diseases. The characteristics of gene drive technologies have raised additional concerns to those for standard genetically engineered organisms. This generates a need for adaptive governance that has not been met yet because of the rapid rate of progress in gene drive research. For the eventual release of gene drive insects into wild populations, an international governance network would be helpful in guiding scientists, stakeholders, public opinion, and affected communities in its use. We examined the current institutions and governing bodies among various continents that could have an impact on gene drive governance or the potential to adapt to its future use. Possible governance strategies also are proposed that seek to bridge gaps and promote an ethically sound policy framework. Ideally, governance strategies should be developed before or at the same pace as gene drive research to anticipate field releases and maximize their impact as a public health tool. However, this is not likely to happen as it takes years to develop global accords, and some countries may choose to move ahead independently on the new technology.


Assuntos
Culicidae/genética , Tecnologia de Impulso Genético/legislação & jurisprudência , Cooperação Internacional/legislação & jurisprudência , Controle de Mosquitos/legislação & jurisprudência , Mosquitos Vetores/genética , Agricultura/ética , Agricultura/métodos , Animais , Animais Geneticamente Modificados , Pesquisa Biomédica/ética , Pesquisa Biomédica/métodos , Tecnologia de Impulso Genético/ética , Humanos , Controle de Mosquitos/organização & administração , Saúde Pública , Característica Quantitativa Herdável
7.
Nat Commun ; 11(1): 3865, 2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32737319

RESUMO

Polygenic scores (PGS) have been widely used to predict disease risk using variants identified from genome-wide association studies (GWAS). To date, most GWAS have been conducted in populations of European ancestry, which limits the use of GWAS-derived PGS in non-European ancestry populations. Here, we derive a theoretical model of the relative accuracy (RA) of PGS across ancestries. We show through extensive simulations that the RA of PGS based on genome-wide significant SNPs can be predicted accurately from modelling linkage disequilibrium (LD), minor allele frequencies (MAF), cross-population correlations of causal SNP effects and heritability. We find that LD and MAF differences between ancestries can explain between 70 and 80% of the loss of RA of European-based PGS in African ancestry for traits like body mass index and type 2 diabetes. Our results suggest that causal variants underlying common genetic variation identified in European ancestry GWAS are mostly shared across continents.


Assuntos
Asma/genética , Diabetes Mellitus Tipo 2/genética , Hipertensão/genética , Modelos Genéticos , Herança Multifatorial , Polimorfismo de Nucleotídeo Único , Adulto , África/epidemiologia , Idoso , Alelos , Ásia/epidemiologia , Asma/diagnóstico , Asma/epidemiologia , Asma/etnologia , Índice de Massa Corporal , Colesterol/sangue , Simulação por Computador , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etnologia , Europa (Continente)/epidemiologia , Feminino , Frequência do Gene , Estudo de Associação Genômica Ampla , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Hipertensão/etnologia , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Prognóstico , Característica Quantitativa Herdável , Risco
8.
Nat Commun ; 11(1): 4020, 2020 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-32782262

RESUMO

While variance components analysis has emerged as a powerful tool in complex trait genetics, existing methods for fitting variance components do not scale well to large-scale datasets of genetic variation. Here, we present a method for variance components analysis that is accurate and efficient: capable of estimating one hundred variance components on a million individuals genotyped at a million SNPs in a few hours. We illustrate the utility of our method in estimating and partitioning variation in a trait explained by genotyped SNPs (SNP-heritability). Analyzing 22 traits with genotypes from 300,000 individuals across about 8 million common and low frequency SNPs, we observe that per-allele squared effect size increases with decreasing minor allele frequency (MAF) and linkage disequilibrium (LD) consistent with the action of negative selection. Partitioning heritability across 28 functional annotations, we observe enrichment of heritability in FANTOM5 enhancers in asthma, eczema, thyroid and autoimmune disorders.


Assuntos
Variação Genética/genética , Genoma Humano/genética , Modelos Genéticos , Alelos , Frequência do Gene , Genótipo , Humanos , Desequilíbrio de Ligação , Herança Multifatorial/genética , Fenótipo , Polimorfismo de Nucleotídeo Único , Característica Quantitativa Herdável
9.
Proc Natl Acad Sci U S A ; 117(32): 18924-18933, 2020 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-32753378

RESUMO

The reconciliation between Mendelian inheritance of discrete traits and the genetically based correlation between relatives for quantitative traits was Fisher's infinitesimal model of a large number of genetic variants, each with very small effects, whose causal effects could not be individually identified. The development of genome-wide genetic association studies (GWAS) raised the hope that it would be possible to identify single polymorphic variants with identifiable functional effects on complex traits. It soon became clear that, with larger and larger GWAS on more and more complex traits, most of the significant associations had such small effects, that identifying their individual functional effects was essentially hopeless. Polygenic risk scores that provide an overall estimate of the genetic propensity to a trait at the individual level have been developed using GWAS data. These provide useful identification of groups of individuals with substantially increased risks, which can lead to recommendations of medical treatments or behavioral modifications to reduce risks. However, each such claim will require extensive investigation to justify its practical application. The challenge now is to use limited genetic association studies to find individually identifiable variants of significant functional effect that can help to understand the molecular basis of complex diseases and traits, and so lead to improved disease prevention and treatment. This can best be achieved by 1) the study of rare variants, often chosen by careful candidate assessment, and 2) the careful choice of phenotypes, often extremes of a quantitative variable, or traits with relatively high heritability.


Assuntos
Estudo de Associação Genômica Ampla , Herança Multifatorial , Variação Genética , Humanos , Modelos Genéticos , Fenótipo , Característica Quantitativa Herdável
10.
Nat Genet ; 52(9): 939-949, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32601472

RESUMO

N6-methyladenosine (m6A) plays important roles in regulating messenger RNA processing. Despite rapid progress in this field, little is known about the genetic determinants of m6A modification and their role in common diseases. In this study, we mapped the quantitative trait loci (QTLs) of m6A peaks in 60 Yoruba (YRI) lymphoblastoid cell lines. We found that m6A QTLs are largely independent of expression and splicing QTLs and are enriched with binding sites of RNA-binding proteins, RNA structure-changing variants and transcriptional features. Joint analysis of the QTLs of m6A and related molecular traits suggests that the downstream effects of m6A are heterogeneous and context dependent. We identified proteins that mediate m6A effects on translation. Through integration with data from genome-wide association studies, we show that m6A QTLs contribute to the heritability of various immune and blood-related traits at levels comparable to splicing QTLs and roughly half of expression QTLs. By leveraging m6A QTLs in a transcriptome-wide association study framework, we identified putative risk genes of these traits.


Assuntos
Adenosina/análogos & derivados , RNA Mensageiro/genética , Adenosina/genética , Mapeamento Cromossômico/métodos , Testes Genéticos/métodos , Variação Genética/genética , Estudo de Associação Genômica Ampla/métodos , Humanos , Fenótipo , Locos de Características Quantitativas/genética , Característica Quantitativa Herdável , Processamento de RNA/genética , Transcriptoma/genética
11.
Anim Sci J ; 91(1): e13417, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32662131

RESUMO

The performance of the two-trait animal model that regards the first parity and later parities as two different traits in estimating genetic parameters for number of born alive (NBA) was examined using real and simulated data. Genetic parameters for NBA were estimated in purebred Landrace and Large White pigs using a single-trait repeatability model (Model 1) that regards all parities as the same trait and a two-trait animal model (Model 2) that regards the first and the later parities as different traits. For Model 2, the permanent environmental effect was fitted to only the records of the later parities. Heritability for NBA estimated using Model 1 was 0.12 for Landrace and 0.11 for Large White. Estimated heritability for NBA of the first parity and the later parities was 0.21 and 0.16, respectively, for Landrace; 0.18 and 0.16, respectively, for Large White obtained using Model 2, and higher than those in both breeds obtained using Model 1. Further results based on data simulated using the Monte Carlo method suggest that estimated additive genetic variance could be more biased using Model 2 than Model 1.


Assuntos
Cruzamento/estatística & dados numéricos , Simulação por Computador , Tamanho da Ninhada de Vivíparos/genética , Modelos Animais , Modelos Genéticos , Paridade/genética , Parto/genética , Animais , Feminino , Método de Monte Carlo , Gravidez , Característica Quantitativa Herdável , Suínos
12.
Anim Sci J ; 91(1): e13426, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32672407

RESUMO

Circulating leptin concentrations could potentially be used as a predictor of production traits in cattle. This study aimed to clarify the correlations between circulating leptin concentrations and growth performance, carcass traits, and meat quality indexes in finishing bulls fed high-concentrate diets (concentrate-to-forage ratio 70:30). Fifty-seven Simmental × Luxi F1 crossbred bulls were used for 112-day finishing experiment. Circulating leptin concentrations and relevant indexes of growth performance, and carcass traits and meat quality were measured during or after finishing trail. The results indicated that the leptin concentrations tended to be negatively correlated with dry matter intake (DMI) (r = -.233, p = .081), and were positively correlated with 12th-rib fat thickness (r = .330, p = .012), marbling score (r = .336, p = .011), and intramuscular fat content (r = .368, p = .021). Moreover, the leptin concentrations were negatively correlated with cholesterol content (r = -.339, p = .037) and were not correlated with sensory indexes including tenderness, juiciness, and like flavor (p > .05). In conclusion, circulating leptin concentrations may potentially be used as a predictor of carcass traits related to content of fat and beef quality traits related to content of cholesterol in finishing bulls fed high-concentrate diets.


Assuntos
Fenômenos Fisiológicos da Nutrição Animal , Bovinos/sangue , Bovinos/crescimento & desenvolvimento , Dieta/veterinária , Qualidade dos Alimentos , Leptina/sangue , Característica Quantitativa Herdável , Carne Vermelha , Animais , Distribuição da Gordura Corporal , Bovinos/genética , Bovinos/metabolismo , Colesterol/sangue , Ingestão de Alimentos , Masculino
13.
Proc Natl Acad Sci U S A ; 117(30): 17680-17687, 2020 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-32665436

RESUMO

Smartphones enjoy high adoption rates around the globe. Rarely more than an arm's length away, these sensor-rich devices can easily be repurposed to collect rich and extensive records of their users' behaviors (e.g., location, communication, media consumption), posing serious threats to individual privacy. Here we examine the extent to which individuals' Big Five personality dimensions can be predicted on the basis of six different classes of behavioral information collected via sensor and log data harvested from smartphones. Taking a machine-learning approach, we predict personality at broad domain ([Formula: see text] = 0.37) and narrow facet levels ([Formula: see text] = 0.40) based on behavioral data collected from 624 volunteers over 30 consecutive days (25,347,089 logging events). Our cross-validated results reveal that specific patterns in behaviors in the domains of 1) communication and social behavior, 2) music consumption, 3) app usage, 4) mobility, 5) overall phone activity, and 6) day- and night-time activity are distinctively predictive of the Big Five personality traits. The accuracy of these predictions is similar to that found for predictions based on digital footprints from social media platforms and demonstrates the possibility of obtaining information about individuals' private traits from behavioral patterns passively collected from their smartphones. Overall, our results point to both the benefits (e.g., in research settings) and dangers (e.g., privacy implications, psychological targeting) presented by the widespread collection and modeling of behavioral data obtained from smartphones.


Assuntos
Aprendizado de Máquina , Personalidade , Smartphone , Comportamento Social , Humanos , Modelos Teóricos , Privacidade , Característica Quantitativa Herdável , Reprodutibilidade dos Testes
14.
PLoS One ; 15(6): e0233752, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32526769

RESUMO

Sugarcane (Saccharum spp.) is an important economic crop, supplying up to 80% of the table sugar and ~60% of bio-ethanol worldwide. Due to population growth and dwindling fossil-fuel reserves, the demand for sugar and bio-ethanol requires significant improvement in sugarcane production. Breeding sugarcane cultivars with high-performance agronomic traits is undoubtedly the most efficient way to achieve this goal. Therefore, evaluating agronomic traits and dissecting underlying loci are critically important for this aim steps in providing genetic resources and molecular markers for selection. In this study, we assembled a diversity panel of 236 elite sugarcane germplasms originally collected from 12 countries. We evaluated 28 agronomic traits in the diversity panel with three replicates. The diversity panel was genotyped using amplified fragment length polymorphism markers, and a total of 1,359 markers were generated. Through the genome-wide association study, we identified three markers significantly associated with three traits evaluated at a stringent threshold (P < 0.05 after Bonferroni correction). The genotypes of the three associated markers grouped respective trait values into two distinct groups, supporting the reliability of these markers for breeding selection. Our study provides putative molecular markers linked to agronomic traits for breeding robust sugarcane cultivars. Additionally, this study emphasized the importance of sugarcane germplasm introduced from other countries and suggested that the use of these germplasms in breeding programs depends on local industrial needs.


Assuntos
Produtos Agrícolas/genética , Polimorfismo Genético , Saccharum/genética , Sementes/genética , Produtos Agrícolas/crescimento & desenvolvimento , Estudo de Associação Genômica Ampla , Melhoramento Vegetal , Locos de Características Quantitativas , Característica Quantitativa Herdável , Saccharum/crescimento & desenvolvimento , Sementes/metabolismo
15.
Proc Biol Sci ; 287(1928): 20201029, 2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-32517627

RESUMO

In social insects, cuticular hydrocarbons function in nest-mate recognition and also provide a waxy barrier against desiccation, but basic evolutionary features, including the heritability of hydrocarbon profiles and how they are shaped by natural selection are largely unknown. We used a new pharaoh ant (Monomorium pharaonis) laboratory mapping population to estimate the heritability of individual cuticular hydrocarbons, genetic correlations between hydrocarbons, and fitness consequences of phenotypic variation in the hydrocarbons. Individual hydrocarbons had low to moderate estimated heritability, indicating that some compounds provide more information about genetic relatedness and can also better respond to natural selection. Strong genetic correlations between compounds are likely to constrain independent evolutionary trajectories, which is expected, given that many hydrocarbons share biosynthetic pathways. Variation in cuticular hydrocarbons was associated with variation in colony productivity, with some hydrocarbons experiencing strong directional selection. Altogether, this study builds on our knowledge of the genetic architecture of the social insect hydrocarbon profile and indicates that hydrocarbon variation is shaped by natural selection.


Assuntos
Formigas/fisiologia , Hidrocarbonetos/metabolismo , Seleção Genética , Animais , Formigas/genética , Característica Quantitativa Herdável
16.
Nat Commun ; 11(1): 2865, 2020 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-32513961

RESUMO

Linking epigenetic marks to clinical outcomes improves insight into molecular processes, disease prediction, and therapeutic target identification. Here, a statistical approach is presented to infer the epigenetic architecture of complex disease, determine the variation captured by epigenetic effects, and estimate phenotype-epigenetic probe associations jointly. Implicitly adjusting for probe correlations, data structure (cell-count or relatedness), and single-nucleotide polymorphism (SNP) marker effects, improves association estimates and in 9,448 individuals, 75.7% (95% CI 71.70-79.3) of body mass index (BMI) variation and 45.6% (95% CI 37.3-51.9) of cigarette consumption variation was captured by whole blood methylation array data. Pathway-linked probes of blood cholesterol, lipid transport and sterol metabolism for BMI, and xenobiotic stimuli response for smoking, showed >1.5 times larger associations with >95% posterior inclusion probability. Prediction accuracy improved by 28.7% for BMI and 10.2% for smoking over a LASSO model, with age-, and tissue-specificity, implying associations are a phenotypic consequence rather than causal.


Assuntos
Epigênese Genética , Característica Quantitativa Herdável , Adulto , Algoritmos , Teorema de Bayes , Biomarcadores/análise , Índice de Massa Corporal , Simulação por Computador , Metilação de DNA/genética , Humanos , Anotação de Sequência Molecular , Especificidade de Órgãos/genética , Reprodutibilidade dos Testes
17.
Genet Sel Evol ; 52(1): 34, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32590928

RESUMO

BACKGROUND: Pasteurellosis (Pasteurella infection) is one of the most common bacterial infections in rabbits on commercial farms and in laboratory facilities. Curative treatments using antibiotics are only partly efficient, with frequent relapses. Breeding rabbits for improved genetic resistance to pasteurellosis is a sustainable alternative approach. In this study, we infected 964 crossbred rabbits from six sire lines experimentally with Pasteurella multocida. After post-mortem examination and bacteriological analyses, abscess, bacteria, and resistance scores were derived for each rabbit based on the extent of lesions and bacterial dissemination in the body. This is the first study to use such an experimental design and response traits to measure resistance to pasteurellosis in a rabbit population. We investigated the genetic variation of these traits in order to identify potential selection criteria. We also estimated genetic correlations of resistance to pasteurellosis in the experimental population with traits that are under selection in the breeding populations (number of kits born alive and weaning weight). RESULTS: Heritability estimates for the novel response traits, abscess, bacteria, and resistance scores, ranged from 0.08 (± 0.05) to 0.16 (± 0.06). The resistance score showed very strong negative genetic correlation estimates with abscess (- 0.99 ± 0.05) and bacteria scores (- 0.98 ± 0.07). A very high positive genetic correlation of 0.99 ± 0.16 was estimated between abscess and bacteria scores. Estimates of genetic correlations of the resistance score with average daily gain traits for the first and second week after inoculation were 0.98 (± 0.06) and 0.70 (± 0.14), respectively. Estimates of genetic correlations of the disease-related traits with average daily gain pre-inoculation were favorable but with high standard errors. Estimates of genetic and phenotypic correlations of the disease-related traits with commercial selection traits were not significantly different from zero. CONCLUSIONS: Disease response traits are heritable and are highly correlated with each other, but do not show any significant genetic correlations with commercial selection traits. Thus, the prevalence of pasteurellosis could be decreased by selecting more resistant rabbits on any one of the disease response traits with a limited impact on the selection traits, which would allow implementation of a breeding program to improve resistance to pasteurellosis in rabbits.


Assuntos
Cruzamento/métodos , Resistência à Doença/genética , Infecções por Pasteurella/genética , Animais , Peso Corporal/genética , Feminino , Genótipo , Masculino , Pasteurella/genética , Pasteurella/patogenicidade , Fenótipo , Característica Quantitativa Herdável , Coelhos , Desmame
18.
Proc Natl Acad Sci U S A ; 117(20): 10769-10777, 2020 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-32376635

RESUMO

Researchers commonly rely on human dental morphological features in order to reconstruct genetic affinities among past individuals and populations, particularly since teeth are often the best preserved part of a human skeleton. Tooth form is considered to be highly heritable and selectively neutral and, therefore, to be an excellent proxy for DNA when none is available. However, until today, it remains poorly understood whether certain dental traits or trait combinations preserve neutral genomic signatures to a greater degree than others. Here, we address this long-standing research gap by systematically testing the utility of 27 common dental traits and >134 million possible trait combinations in reflecting neutral genomic variation in a worldwide sample of modern human populations. Our analyses reveal that not all traits are equally well-suited for reconstructing population affinities. Whereas some traits largely reflect neutral variation and therefore evolved primarily as a result of genetic drift, others can be linked to nonstochastic processes such as natural selection or hominin admixture. We also demonstrate that reconstructions of population affinity based on many traits are not necessarily more reliable than those based on only a few traits. Importantly, we find a set of highly diagnostic trait combinations that preserve neutral genetic signals best (up to [Formula: see text] r = 0.580; 95% r range = 0.293 to 0.758; P = 0.001). We propose that these trait combinations should be prioritized in future research, as they allow for more accurate inferences about past human population dynamics when using dental morphology as a proxy for DNA.


Assuntos
Variação Genética , Genética Populacional/métodos , Característica Quantitativa Herdável , Dente/anatomia & histologia , Genética Populacional/normas , Humanos
19.
Nat Commun ; 11(1): 2085, 2020 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-32350251

RESUMO

Allopolyploidy generates diversity by increasing the number of copies and sources of chromosomes. Many of the best-known evolutionary radiations, crops, and industrial organisms are ancient or recent allopolyploids. Allopolyploidy promotes differentiation and facilitates adaptation to new environments, but the tools to test its limits are lacking. Here we develop an iterative method of Hybrid Production (iHyPr) to combine the genomes of multiple budding yeast species, generating Saccharomyces allopolyploids of at least six species. When making synthetic hybrids, chromosomal instability and cell size increase dramatically as additional copies of the genome are added. The six-species hybrids initially grow slowly, but they rapidly regain fitness and adapt, even as they retain traits from multiple species. These new synthetic yeast hybrids and the iHyPr method have potential applications for the study of polyploidy, genome stability, chromosome segregation, and bioenergy.


Assuntos
Hibridização Genética , Saccharomyces/genética , Evolução Molecular Direcionada , Tamanho do Genoma , Genoma Fúngico , Instabilidade Genômica , Genótipo , Padrões de Herança/genética , Mitocôndrias/genética , Fenótipo , Característica Quantitativa Herdável
20.
PLoS Genet ; 16(5): e1008612, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32427991

RESUMO

Estimating the polygenicity (proportion of causally associated single nucleotide polymorphisms (SNPs)) and discoverability (effect size variance) of causal SNPs for human traits is currently of considerable interest. SNP-heritability is proportional to the product of these quantities. We present a basic model, using detailed linkage disequilibrium structure from a reference panel of 11 million SNPs, to estimate these quantities from genome-wide association studies (GWAS) summary statistics. We apply the model to diverse phenotypes and validate the implementation with simulations. We find model polygenicities (as a fraction of the reference panel) ranging from ≃ 2 × 10-5 to ≃ 4 × 10-3, with discoverabilities similarly ranging over two orders of magnitude. A power analysis allows us to estimate the proportions of phenotypic variance explained additively by causal SNPs reaching genome-wide significance at current sample sizes, and map out sample sizes required to explain larger portions of additive SNP heritability. The model also allows for estimating residual inflation (or deflation from over-correcting of z-scores), and assessing compatibility of replication and discovery GWAS summary statistics.


Assuntos
Estudos de Associação Genética , Heterogeneidade Genética , Padrões de Herança/fisiologia , Modelos Genéticos , Polimorfismo de Nucleotídeo Único , Simulação por Computador , Estudos de Associação Genética/métodos , Estudos de Associação Genética/estatística & dados numéricos , Genética Populacional , Estudo de Associação Genômica Ampla/métodos , Estudo de Associação Genômica Ampla/estatística & dados numéricos , Heterozigoto , Humanos , Desequilíbrio de Ligação , Herança Multifatorial , Distribuição Normal , Fenótipo , Característica Quantitativa Herdável
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