Progress of genome wide association study in domestic animals

Domestic animals are invaluable resources for study of the molecular architecture of complex traits. Although the mapping of quantitative trait loci (QTL) responsible for economically important traits in domestic animals has achieved remarkable results in recent decades, not all of the genetic variation in the complex traits has been captured because of the low density of markers used in QTL mapping studies. The genome wide association study (GWAS), which utilizes high-density single-nucleotide polymorphism (SNP), provides a new way to tackle this issue. Encouraging achievements in dissection of the genetic mechanisms of complex diseases in humans have resulted from the use of GWAS. At present, GWAS has been applied to the field of domestic animal breeding and genetics, and some advances have been made. Many genes or markers that affect economic traits of interest in domestic animals have been identified. In this review, advances in the use of GWAS in domestic animals are described

Genome-Wide Association Study and Selective Sweep Analysis Reveal the Genetic Architecture of Body Weights in a Chicken F2 Resource Population

Rapid growth is one of the most important economic traits in broiler breeding programs. Identifying markers and genes for growth traits may not only benefit marker-assisted selection (MAS)/genomic selection (GS) but also provide important information for understanding the genetic architecture of growth traits in broilers. In the present study, an F2 resource population derived from a cross between the broiler and Baier yellow chicken (a Chinese local breed) was used and body weights from 1 to 12 weeks of age [body weight (BW) 1–BW12)] were measured. A total of 519 F2 birds were genome re-sequenced, and a combination of genome-wide association study (GWAS) and selective sweep analysis was carried out to characterize the genetic architecture affecting chicken body weight comprehensively. As a result, 1,539 SNPs with significant effects on body weights at different weeks of age were identified using a genome-wide efficient mixed-model association (GEMMA) package. These SNPs were distributed on chromosomes 1 and 4. Besides, windows under selection identified for BW1–BW12 varied from 1,581 to 2,265. A total of 42 genes were also identified with significant effects on BW1–BW12 based on both GWAS and selective sweep analysis. Among these genes, diacylglycerol kinase eta (DGKH), deleted in lymphocytic leukemia (DLEU7), forkhead box O17 (FOXO1), karyopherin subunit alpha 3 (KPNA3), calcium binding protein 39 like (CAB39L), potassium voltage-gated channel interacting protein 4 (KCNIP4), and slit guidance ligand 2 (SLIT2) were considered as important genes for broiler growth based on their basic functions. The results of this study may supply important information for understanding the genetic architecture of growth traits in broilers

Differential expression of six genes and correlation with fatness traits in a unique broiler population

AbstractPrevious results from genome wide association studies (GWASs) in chickens divergently selected for abdominal fat content of Northeast Agricultural University (NEAUHLF) showed that many single nucleotide polymorphism (SNP) variants were associated with abdominal fat content. Of them, six top significant SNPs at the genome level were located within SRD5A3, SGCZ, DLC1, GBE1, GALNT9 and DNAJB6 genes. Here, expression levels of these six candidate genes were investigated in abdominal fat and liver tissue between fat and lean broilers from the 14th generation population of NEAUHLF. The results showed that expression levels of SRD5A3, SGCZ and DNAJB6 in the abdominal fat and SRD5A3, DLC1, GALNT9, DNAJB6 and GBE1 in the liver tissue differed significantly between the fat and lean birds, and were correlated with abdominal fat traits. The findings will provide important references for further function investigation of the six candidate genes involved in abdominal fat deposition in chickens

Integration of the Vegetation Phenology Module Improves Ecohydrological Simulation by the SWAT-Carbon Model

Vegetation phenology and hydrological cycles are closely interacted from leaf and species levels to watershed and global scales. As one of the most sensitive biological indicators of climate change, plant phenology is essential to be simulated accurately in hydrological models. Despite the Soil and Water Assessment Tool (SWAT) has been widely used for estimating hydrological cycles, its lack of integration with the phenology module has led to substantial uncertainties. In this study, we developed a process-based vegetation phenology module and coupled it with the SWAT-Carbon model to investigate the effects of vegetation dynamics on runoff in the upper reaches of Jinsha River watershed in China. The modified SWAT-Carbon model showed reasonable performance in phenology simulation, with root mean square error (RMSE) of 9.89 days for the start-of-season (SOS) and 7.51 days for the end-of-season (EOS). Simulations of both vegetation dynamics and runoff were also substantially improved compared to the original model. Specifically, the simulation of leaf area index significantly improved with the coefficient of determination (R2) increased by 0.62, the Nash–Sutcliffe efficiency (NSE) increased by 2.45, and the absolute percent bias (PBIAS) decreased by 69.0 % on average. Additionally, daily runoff simulation also showed notably improvement, particularly noticeable in June and October, with R2 rising by 0.22 and NSE rising by 0.43 on average. Our findings highlight the importance of integrating vegetation phenology into hydrological models to enhance modeling performance

Evaluation of the efficacy and safety of intravenous remdesivir in adult patients with severe COVID-19: study protocol for a phase 3 randomized, double-blind, placebo-controlled, multicentre trial.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by a novel corinavirus (later named SARS-CoV-2 virus), was fistly reported in Wuhan, Hubei Province, China towards the end of 2019. Large-scale spread within China and internationally led the World Health Organization to declare a Public Health Emergency of International Concern on 30th January 2020. The clinical manifestations of COVID-19 virus infection include asymptomatic infection, mild upper respiratory symptoms, severe viral pneumonia with respiratory failure, and even death. There are no antivirals of proven clinical efficacy in coronavirus infections. Remdesivir (GS-5734), a nucleoside analogue, has inhibitory effects on animal and human highly pathogenic coronaviruses, including MERS-CoV and SARS-CoV, in in vitro and in vivo experiments. It is also inhibitory against the COVID-19 virus in vitro. The aim of this study is to assess the efficacy and safety of remdesivir in adult patients with severe COVID-19. METHODS: The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. This is a phase 3, randomized, double-blind, placebo-controlled, multicentre trial. Adults (≥ 18 years) with laboratory-confirmed COVID-19 virus infection, severe pneumonia signs or symptoms, and radiologically confirmed severe pneumonia are randomly assigned in a 2:1 ratio to intravenously administered remdesivir or placebo for 10 days. The primary endpoint is time to clinical improvement (censored at day 28), defined as the time (in days) from randomization of study treatment (remdesivir or placebo) until a decline of two categories on a six-category ordinal scale of clinical status (1 = discharged; 6 = death) or live discharge from hospital. One interim analysis for efficacy and futility will be conducted once half of the total number of events required has been observed. DISCUSSION: This is the first randomized, placebo-controlled trial in COVID-19. Enrolment began in sites in Wuhan, Hubei Province, China on 6th February 2020. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04257656. Registered on 6 February 2020

Association of inpatient use of angiotensin converting enzyme inhibitors and angiotensin II receptor blockers with mortality among patients with hypertension hospitalized with COVID-19

Rationale: Use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) is a major concern for clinicians treating coronavirus disease 2019 (COVID-19) in patients with hypertension. Objective: To determine the association between in-hospital use of ACEI/ARB and all-cause mortality in COVID-19 patients with hypertension. Methods and Results: This retrospective, multi-center study included 1128 adult patients with hypertension diagnosed with COVID-19, including 188 taking ACEI/ARB (ACEI/ARB group; median age 64 [IQR 55-68] years; 53.2% men) and 940 without using ACEI/ARB (non-ACEI/ARB group; median age 64 [IQR 57-69]; 53.5% men), who were admitted to nine hospitals in Hubei Province, China from December 31, 2019 to February 20, 2020. Unadjusted mortality rate was lower in the ACEI/ARB group versus the non-ACEI/ARB group (3.7% vs. 9.8%; P = 0.01). In mixed-effect Cox model treating site as a random effect, after adjusting for age, gender, comorbidities, and in-hospital medications, the detected risk for all-cause mortality was lower in the ACEI/ARB group versus the non-ACEI/ARB group (adjusted HR, 0.42; 95% CI, 0.19-0.92; P =0.03). In a propensity score-matched analysis followed by adjusting imbalanced variables in mixed-effect Cox model, the results consistently demonstrated lower risk of COVID-19 mortality in patients who received ACEI/ARB versus those who did not receive ACEI/ARB (adjusted HR, 0.37; 95% CI, 0.15-0.89; P = 0.03). Further subgroup propensity score-matched analysis indicated that, compared to use of other antihypertensive drugs, ACEI/ARB was also associated with decreased mortality (adjusted HR, 0.30; 95%CI, 0.12-0.70; P = 0.01) in COVID-19 patients with hypertension. Conclusions: Among hospitalized COVID-19 patients with hypertension, inpatient use of ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB non-users. While study interpretation needs to consider the potential for residual confounders, it is unlikely that in-hospital use of ACEI/ARB was associated with an increased mortality risk

Construction of biorthogonal multiwavelets

AbstractThere are perfect formulas for the constructions of biorthogonal uniwavelets. Let φ(x)=∑k∈Zpkφ(2x−k),φ̃(x)=∑k∈Zp̃kφ̃(2x−k) be a pair of biorthogonal uniscaling functions, then a pair of biorthogonal uniwavelet associated with the above biorthogonal uniscaling functions can be easily expressed as ψ(x)=∑k∈Z(−1)k−1p̃1−kφ(2x−k),ψ̃(x)=∑k∈Z(−1)k−1p1−kφ̃(2x−k). However, it seems that there is not such a good formula of similar structure for biorthogonal multiwavelets. In this paper, we will give a procedure for constructing compactly supported biorthogonal multiwavelets, which makes construction of biorthogonal multiwavelets easy like in the construction of biorthogonal uniwavelet. Our approach is also suitable for the case of compactly supported orthogonal multiwavelets. Four examples for constructing multiwavelets are given