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1.
BMC Genomics ; 22(1): 538, 2021 Jul 13.
Article in English | MEDLINE | ID: mdl-34256689

ABSTRACT

BACKGROUND: Although inbreeding caused by the mating of animals related through a recent common ancestor is expected to have more harmful effects on phenotypes than ancient inbreeding (old inbreeding), estimating these effects requires a clear definition of recent (new) and ancient (old) inbreeding. Several methods have been proposed to classify inbreeding using pedigree and genomic data. Unfortunately, these methods are largely based on heuristic criteria such as the number of generations from a common ancestor or length of runs of homozygosity (ROH) segments. To mitigate these deficiencies, this study aimed to develop a method to classify pedigree and genomic inbreeding into recent and ancient classes based on a grid search algorithm driven by the assumption that new inbreeding tends to have a more pronounced detrimental effect on traits. The proposed method was tested using a cattle population characterized by a deep pedigree. RESULTS: Effects of recent and ancient inbreeding were assessed on four growth traits (birth, weaning and yearling weights and average daily gain). Thresholds to classify inbreeding into recent and ancient classes were trait-specific and varied across traits and sources of information. Using pedigree information, inbreeding generated in the last 10 to 11 generations was considered as recent. When genomic information (ROH) was used, thresholds ranged between four to seven generations, indicating, in part, the ability of ROH segments to characterize the harmful effects of inbreeding in shorter periods of time. Nevertheless, using the proposed classification method, the discrimination between new and old inbreeding was less robust when ROH segments were used compared to pedigree. Using several model comparison criteria, the proposed approach was generally better than existing methods. Recent inbreeding appeared to be more harmful across the growth traits analyzed. However, both new and old inbreeding were found to be associated with decreased yearling weight and average daily gain. CONCLUSIONS: The proposed method provided a more objective quantitative approach for the classification of inbreeding. The proposed method detected a clear divergence in the effects of old and recent inbreeding using pedigree data and it was superior to existing methods for all analyzed traits. Using ROH data, the discrimination between old and recent inbreeding was less clear and the proposed method was superior to existing approaches for two out of the four analyzed traits. Deleterious effects of recent inbreeding were detected sooner (fewer generations) using genomic information than pedigree. Difference in the results using genomic and pedigree information could be due to the dissimilarity in the number of generations to a common ancestor. Additionally, the uncertainty associated with the identification of ROH segments and associated inbreeding could have an effect on the results. Potential biases in the estimation of inbreeding effects may occur when new and old inbreeding are discriminated based on arbitrary thresholds. To minimize the impact of inbreeding, mating designs should take the different inbreeding origins into consideration.


Subject(s)
Inbreeding , Polymorphism, Single Nucleotide , Animals , Cattle/genetics , Genomics , Homozygote , Pedigree , Phenotype
2.
Anim Biotechnol ; 31(3): 203-208, 2020 Jun.
Article in English | MEDLINE | ID: mdl-30950314

ABSTRACT

The dietary requirement for cysteine is not determined in poultry since it is not an essential amino acid. The cysteine need is expected to be met through the transsulfuration pathway where homocysteine, a precursor of methionine, is converted to cysteine. Cysteine is a major component of plumage, and the degree to which cysteine is involved in plumage and other keratized proteins are unknown. We randomly assigned chicks to control and treatment (deficient in cysteine) diets for 49 d. The thickness of the skin layers, feather follicle length, and thickness were measured at days 10, 24, 34, and 49. We also measured the hepatic mRNA expressions of cystathionine beta synthase (CBS), cystathionine γ-lyase (CTL), cysteine dioxygenase (CDO), and glutathione synthetase (GSS). Chickens fed the treatment diet had reduced epidermis thickness and shorter feather follicles compared with the controls. The chicken fed the treatment diet also had increased mRNA expression of CBS and CTL indicating a disruption of the transsulfuration pathway. The treatment chickens also had a decreased hepatic CDO and increased GSS mRNA expressions which are in concordance with the homeostatic regulation of cysteine. Compromised cysteine metabolism could affect thermoregulation and subsequently affect feed efficiency and welfare of the birds.


Subject(s)
Cysteine , Diet/veterinary , Feathers , Glutathione/metabolism , Skin , Animals , Chickens , Cysteine/metabolism , Cysteine/pharmacology , Feathers/chemistry , Feathers/drug effects , Feathers/growth & development , Feathers/metabolism , Male , Metabolic Networks and Pathways/drug effects , Metabolic Networks and Pathways/genetics , Skin/chemistry , Skin/drug effects , Skin/growth & development , Skin/metabolism , Sulfur/metabolism
3.
BMC Genet ; 20(1): 21, 2019 02 22.
Article in English | MEDLINE | ID: mdl-30795734

ABSTRACT

BACKGROUND: It becomes clear that the increase in the density of marker panels and even the use of sequence data didn't result in any meaningful increase in the accuracy of genomic selection (GS) using either regression (RM) or variance component (VC) approaches. This is in part due to the limitations of current methods. Association model are well over-parameterized and suffer from severe co-linearity and lack of statistical power. Even when the variant effects are not directly estimated using VC based approaches, the genomic relationships didn't improve after the marker density exceeded a certain threshold. SNP prioritization-based fixation index (FST) scores were used to track the majority of significant QTL and to reduce the dimensionality of the association model. RESULTS: Two populations with average LD between adjacent markers of 0.3 (P1) and 0.7 (P2) were simulated. In both populations, the genomic data consisted of 400 K SNP markers distributed on 10 chromosomes. The density of simulated genomic data mimics roughly 1.2 million SNP markers in the bovine genome. The genomic relationship matrix (G) was calculated for each set of selected SNPs based on their FST score and similar numbers of SNPs were selected randomly for comparison. Using all 400 K SNPs, 46% of the off-diagonal elements (OD) were between - 0.01 and 0.01. The same portion was 31, 23 and 16% when 80 K, 40 K and 20 K SNPs were selected based on FST scores. For randomly selected 20 K SNP subsets, around 33% of the OD fell within the same range. Genomic similarity computed using SNPs selected based on FST scores was always higher than using the same number of SNPs selected randomly. Maximum accuracies of 0.741 and 0.828 were achieved when 20 and 10 K SNPs were selected based on FST scores in P1 and P2, respectively. CONCLUSIONS: Genomic similarity could be maximized by the decrease in the number of selected SNPs, but it also leads to a decrease in the percentage of genetic variation explained by the selected markers. Finding the balance between these two parameters could optimize the accuracy of GS in the presence of high density marker panels.


Subject(s)
Breeding , Genetic Markers/genetics , Genomics , Polymorphism, Genetic , Animals , Body Weight/genetics , Linkage Disequilibrium , Livestock/genetics , Polymorphism, Single Nucleotide , Quantitative Trait Loci/genetics , Weaning
4.
Anim Biotechnol ; 30(2): 175-179, 2019 Apr.
Article in English | MEDLINE | ID: mdl-29708051

ABSTRACT

Cysteine is a nonessential amino acid in poultry nutrition. Poultry diets are deficient in cysteine, but the bird's cysteine need is met through the transsulfuration pathway (TSP) where homocysteine is converted to cysteine: a process catalyzed by cystathionine ß-synthase (CBS) and cystathionine γ-lyase (CTH). Cysteine is also a major component of keratinized protein found in feathers, but the extent to which cysteine is involved in feather and skin development in poultry is unknown. We randomly assigned chicks to control and treatment (control diet plus 100 mg/kg body weight of propargylglycine which is an inhibitor of CTH) diets. The thickness of skin layers, primary feather follicle parameters, growth, and mRNA expression of CBS and CTH were measured. Inhibition of TSP corresponded with the upregulation of liver mRNA of both CBS and CTH and reduction in growth from 35 to 40 days of age. The epidermis thickness, feather follicle length, and diameter were reduced from 10 to 40 days of age. Incorporation of cysteine into keratinized protein may be more sensitive to the level of available cysteine than into nonkeratinized proteins. Thus, disruption of the TSP could affect the thermoregulatory ability of the bird.


Subject(s)
Alkynes/pharmacology , Chickens/metabolism , Cystathionine beta-Synthase/metabolism , Cystathionine gamma-Lyase/antagonists & inhibitors , Enzyme Inhibitors/pharmacology , Glycine/analogs & derivatives , Metabolic Networks and Pathways/drug effects , Animals , Chickens/genetics , Chickens/growth & development , Cystathionine beta-Synthase/genetics , Cystathionine gamma-Lyase/genetics , Cystathionine gamma-Lyase/metabolism , Cysteine/deficiency , Diet/veterinary , Feathers/drug effects , Feathers/growth & development , Gene Expression Regulation, Developmental/drug effects , Glycine/pharmacology , Liver/drug effects , Random Allocation , Skin/drug effects , Sulfur/metabolism , Up-Regulation/drug effects
5.
Int J Biometeorol ; 63(12): 1569-1584, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31352522

ABSTRACT

Heat stress (HS) causes oxidative stress and cellular changes in an attempt to detoxify the harmful effects of reactive oxygen species (ROS). However, how ROS affect different organs in chickens under acute and chronic HS is relatively unknown. We investigated the cellular enzyme activity and biomarker changes in the liver and Pectoralis (P) major muscle in broiler chickens subjected to both acute and chronic HS. Forty-eight broiler chickens at 14 days old were randomly assigned to either 25 °C (control) or 35 °C (heat-stressed) for 12 days. Five birds per treatment at 1 and 12 days post-HS were euthanized, and the liver and P. major muscle were sampled. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione (GSH), glutathione reductase (GR), glutathione S-transferase (GST) activity as well as 8-hydroxy-2'-deoxyguanosine (8-OHdG), advanced glycation end product (AGE), malondialdehyde (MDA), and protein carbonyl (PCO) were analyzed as biomarkers for DNA, carbohydrate, lipid, and protein oxidation, respectively. The SOD, CAT, and GSH-GPx activity levels in the liver and the P. major muscle changed under HS; however, some of the changes were tissue-specific or dependent on the duration of the HS. There were increased liver 8-OHdG during chronic HS and also increased liver AGE levels during both acute and chronic HS indicating significant carbohydrate and DNA oxidations. In the P. major muscle, we observed significant increases in lipid peroxidation and protein oxidation which may reflect that this tissue is less resilient to oxidative damage under heat stress. We show that heat stress caused tissue-specific changes to levels of oxidation biomarkers in chicken.


Subject(s)
Antioxidants , Chickens , Animals , Biomarkers , Catalase , Glutathione , Glutathione Peroxidase , Heat-Shock Response , Lipid Peroxidation , Oxidative Stress , Superoxide Dismutase
6.
BMC Genet ; 19(1): 13, 2018 02 15.
Article in English | MEDLINE | ID: mdl-29448946

ABSTRACT

CORRECTION TO: BMC GENETICS (2018) 19:4 DOI: 10.1186/S12863-017-0595-2: The original version of this article [1], published on 5 January 2018, contained 3 formatting errors. In this Correction the affected parts of the article are shown. The original article has been updated.

7.
BMC Genet ; 19(1): 4, 2018 01 05.
Article in English | MEDLINE | ID: mdl-29304753

ABSTRACT

BACKGROUND: The availability of high-density (HD) marker panels, genome wide variants and sequence data creates an unprecedented opportunity to dissect the genetic basis of complex traits, enhance genomic selection (GS) and identify causal variants of disease. The disproportional increase in the number of parameters in the genetic association model compared to the number of phenotypes has led to further deterioration in statistical power and an increase in co-linearity and false positive rates. At best, HD panels do not significantly improve GS accuracy and, at worst, reduce accuracy. This is true for both regression and variance component approaches. To remedy this situation, some form of single nucleotide polymorphisms (SNP) filtering or external information is needed. Current methods for prioritizing SNP markers (i.e. BayesB, BayesCπ) are sensitive to the increased co-linearity in HD panels which could limit their performance. RESULTS: In this study, the usefulness of FST, a measure of allele frequency variation among populations, as an external source of information in GS was evaluated. A simulation was carried out for a trait with heritability of 0.4. Data was divided into three subpopulations based on phenotype distribution (bottom 5%, middle 90%, top 5%). Marker data were simulated to mimic a 770 K and 1.5 million SNP marker panel. A ten-chromosome genome with 200 K and 400 K SNPs was simulated. Several scenarios with varying distributions for the quantitative trait loci (QTL) effects were simulated. Using all 200 K markers and no filtering, the accuracy of genomic prediction was 0.77. When marker effects were simulated from a gamma distribution, SNPs pre-selected based on the 99.5, 99.0 and 97.5% quantile of the FST score distribution resulted in an accuracy of 0.725, 0.797, and 0.853, respectively. Similar results were observed under other simulation scenarios. Clearly, the accuracy obtained using all SNPs can be easily achieved using only 0.5 to 1% of all markers. CONCLUSIONS: These results indicate that SNP filtering using already available external information could increase the accuracy of GS. This is especially important as next-generation sequencing technology becomes more affordable and accessible to human, animal and plant applications.


Subject(s)
Models, Genetic , Polymorphism, Single Nucleotide , Selection, Genetic , Animals , Breeding , Female , Genetics, Population , Humans , Male , Plants/genetics , Quantitative Trait, Heritable
8.
Mol Biol Rep ; 45(3): 389-394, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29619655

ABSTRACT

Heat stress causes critical molecular dysfunction that affects productivity in chickens. Thus, the purpose of this study was to evaluate the effect of heat stress (HS) on the expression of select genes in the oxidation/antioxidation machinery in the liver of chickens. Chickens at 14 days of age were randomly assigned to two treatment groups and kept under either a constant normal temperature (25 °C) or high temperature (35 °C) in individual cages for 12 days. mRNA expression of Nrf2, oxidants NADPH(NOX): [NOX1, NOX2, NOX3, NOX4, NOX5 and DUOX2], and antioxidants [SOD1, CAT, GR, GPx1, NQO1] in the liver were analyzed at 1 and 12 days post-HS. We show that, HS changes the mRNA expression of oxidants thereby increasing cellular reactive oxygen species (ROS). Additionally, persistent HS up-regulates SOD which converts superoxides to hydrogen peroxide. We further demonstrated the dynamic relationship between catalase, GSH peroxidase (GPx) and NADPH under both acute and chronic heat stress. The pentose phosphate pathway could be important under HS since it generates NADPH which serves as a cofactor for GPx. Also, methionine, a precursor of cysteine has been shown to have reducing properties and thereby makes for an alternative fuel for redox processes. Genes in the ROS and antioxidant generation pathways may provide insight into nutritional intervention strategies, especially the use of methionine and/or cysteine when birds are suffering from heat stress.


Subject(s)
Chickens/genetics , Heat-Shock Response/genetics , Liver/metabolism , Animals , Antioxidants/metabolism , Catalase/metabolism , Gene Expression Profiling/methods , Glutathione/metabolism , Glutathione Peroxidase/genetics , Glutathione Peroxidase/metabolism , Hot Temperature/adverse effects , Hydrogen Peroxide/metabolism , Male , NADP/metabolism , Oxidants/metabolism , Oxidation-Reduction/drug effects , Oxidative Stress/drug effects , Pentose Phosphate Pathway/genetics , Pentose Phosphate Pathway/physiology , Reactive Oxygen Species/metabolism
9.
Int J Biometeorol ; 61(12): 2111-2118, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28799035

ABSTRACT

The aim of this study was to investigate the effect of heat stress (HS) on digestibility of protein and fat and the expression of nutrient transporters in broilers. Forty-eight male Cobb500 chicks were used in this study. At day 14, birds were randomly divided into two groups and kept under either constant normal temperature (25 °C) or high temperature (35 °C) in individual cages. Five birds per treatment at 1 and 12 days post-treatment were euthanized, and Pectoralis major (P. major) and ileum were sampled for gene expression analysis. At day 33, ileal contents were collected and used for digestibility analysis. The total consumption and retention of protein and fat were significantly lower in the HS group compared to the control group. Meanwhile, the retention of crude protein per BWG was significantly higher in the HS group compared to the control group. In P. major and ileum tissues at day 1, transporters FATP1 and SGLT1 were down-regulated in the HS group. Meanwhile, FABP1 and PepT1 were down-regulated only in the ileum of the HS group. The converse was shown in P. major. The nutrient transporter FABP1 at day 12 post-HS was down-regulated in the P. major and ileum, but GLUT1 and PepT2 were down-regulated only in the ileum, and PepT1 was down-regulated only in the P. major compared with the control group. These changes in nutrient transporters suggest that high ambient temperature might change the ileum and P. major lipids, glucose, and oligopeptide transporters.


Subject(s)
Chickens , Dietary Proteins , Fatty Acid-Binding Proteins/genetics , Heat Stress Disorders/genetics , Pectoralis Muscles/metabolism , Peptide Transporter 1/genetics , Animals , Avian Proteins/genetics , Chickens/genetics , Chickens/metabolism , Dietary Fats , Down-Regulation , Energy Metabolism , Gene Expression , Heat Stress Disorders/metabolism , Heat Stress Disorders/veterinary , Hot Temperature/adverse effects , Ileum/metabolism , Male , Poultry Products
10.
Mol Genet Genomics ; 290(5): 1673-82, 2015 Oct.
Article in English | MEDLINE | ID: mdl-25782841

ABSTRACT

Feed efficiency phenotypes defined by genotypes or gene markers are unknown. To date, there are only limited studies on global gene expression profiling on feed efficiency. The objective of this study was to identify genes and pathways associated with residual feed intake (RFI) through transcriptional profiling of duodenum at two different ages in a chicken population divergently selected for low (LRFI) or high (HRFI) RFI. The global gene expression differences in LRFI and HRFI were assessed by the Affymetrix GeneChip(®) Chicken Genome Array and RT-PCR using duodenal tissue on days 35 and 42. The Ingenuity Pathway Analysis program was used to identify canonical and gene network pathways associated with RFI. A global view of gene expression differences between LRFI and HRFI suggest that RFI can be explained by differences in cell division, growth, proliferation and apoptosis, protein synthesis, lipid metabolism, and molecular transport of cellular molecules. Chickens selected for improved RFI achieve efficiency by reducing feed intake with a nominal or no change in weight gain by either up-regulating CD36, PPARα, HMGCS2, GCG or down-regulating PCSK2, CALB1, SAT1, and SGK1 genes within the lipid metabolism, small molecule biochemistry, molecular transport, cell death, and protein synthesis molecular and cellular functions. Chickens selected for reduced RFI via reduced feed intake with no change in weight gain achieve feed efficiency for growth by the up-regulation of genes that reduce appetite with increased cellular oxidative stress, prolonged cell cycle, DNA damage, and apoptosis in addition to increased oxidation of dietary fat and efficient fatty acids transported from the intestines.


Subject(s)
Animal Feed , Chickens/physiology , Poultry Products , Transcriptome , Animals , Chickens/genetics , Chickens/growth & development , Gene Expression Profiling , Transcription, Genetic
11.
PLoS One ; 19(2): e0296350, 2024.
Article in English | MEDLINE | ID: mdl-38394169

ABSTRACT

Eimeria (E.) maxima parasite infects chickens' midgut disrupting the jejunal and ileal mucosa causing high morbidity and mortality. Heat stress (HS) is a seasonal stressor that impacts biological functions leading to poor performance. This study elucidates how HS, E. maxima infection, and their combination affect the ileum transcriptome. Two-hundred and forty 2-week-old males Ross708 chickens were randomly allocated into four treatment groups: thermoneutral-control (TNc), thermoneutral-infected (TNi), heat-stress control (HSc), and heat stress-infected (HSi), with 6 replicates each of 10 birds. Infected groups received 200x103 sporulated E. maxima oocysts/bird, and heat-treated groups were raised at 35°C. At 6-day post-treatment, ileums of five randomly selected chickens per group were sampled, RNA was extracted and sequenced. A total of 413, 3377, 1908, and 2304 DEGs were identified when applying the comparisons: TNc vs HSc, TNc vs TNi, HSi vs HSc, and TNi vs HSi, respectively, at cutoff ≥1.2-fold change (FDR: q<0.05). HSc vs TNc showed upregulation of lipid metabolic pathways and degradation/metabolism of multiple amino acids; and downregulation of most immune-related and protein synthesis pathways. TNc vs TNi displayed upregulation of most of immune-associated pathways and eukaryotic mRNA maturation pathways; and downregulation of fatty acid metabolism and multiple amino acid metabolism pathways including tryptophan. Comparing HSi versus HSc and TNi revealed that combining the two stressors restored the expression of some cellular functions, e.g., oxidative phosphorylation and protein synthesis; and downregulate immune response pathways associated with E. maxima infection. During E. maxima infection under HS the calcium signaling pathway was downregulated, including genes responsible for increasing the cytoplasmic calcium concentration; and tryptophan metabolism was upregulated, including genes that contribute to catabolizing tryptophan through serotonin and indole pathways; which might result in reducing the cytoplasmic pool of nutrients and calcium available for the parasite to scavenge and consequently might affect the parasite's reproductive ability.


Subject(s)
Coccidiosis , Eimeria , Poultry Diseases , Male , Animals , Eimeria/genetics , Chickens/genetics , Transcriptome , Tryptophan/genetics , Calcium , Immunity , Heat-Shock Response/genetics , Meat
12.
Biostatistics ; 13(2): 217-27, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22285993

ABSTRACT

Single-nucleotide polymorphisms (SNPs), believed to determine human differences, are widely used to predict risk of diseases. Typically, clinical samples are limited and/or the sampling cost is high. Thus, it is essential to determine an adequate sample size needed to build a classifier based on SNPs. Such a classifier would facilitate correct classifications, while keeping the sample size to a minimum, thereby making the studies cost-effective. For coded SNP data from 2 classes, an optimal classifier and an approximation to its probability of correct classification (PCC) are derived. A linear classifier is constructed and an approximation to its PCC is also derived. These approximations are validated through a variety of Monte Carlo simulations. A sample size determination algorithm based on the criterion, which ensures that the difference between the 2 approximate PCCs is below a threshold, is given and its effectiveness is illustrated via simulations. For the HapMap data on Chinese and Japanese populations, a linear classifier is built using 51 independent SNPs, and the required total sample sizes are determined using our algorithm, as the threshold varies. For example, when the threshold value is 0.05, our algorithm determines a total sample size of 166 (83 for Chinese and 83 for Japanese) that satisfies the criterion.


Subject(s)
Polymorphism, Single Nucleotide , Algorithms , Asian People/classification , Asian People/genetics , Biostatistics , Genetics, Population/statistics & numerical data , HapMap Project , Humans , Models, Statistical , Monte Carlo Method , Probability , Sample Size
13.
Bioinformatics ; 28(3): 403-10, 2012 Feb 01.
Article in English | MEDLINE | ID: mdl-22135417

ABSTRACT

MOTIVATION: Recently, gene-coexpression relationships have been found to be often conditional and dynamic. Many studies have suggested that single nucleotide polymorphisms (SNPs) have impacts on gene expression variations in human populations. RESULTS: The SNPxGE(2) database contains the computationally predicted human SNP-coexpression associations, i.e. the differential coexpression between two genes is associated with the genotypes of an SNP. These data were generated from a large-scale association study that was based on the HapMap phase I data, which covered 269 individuals from 4 human populations, 556 873 SNPs and 15 000 gene expression profiles. In order to reduce the computational cost, the SNP-coexpression associations were assessed using gap/substitution models, proven to have a comparable power to logistic regression models. The results, at a false discovery rate (FDR) cutoff of 0.1, consisted of 44 769 and 50 792 SNP-coexpression associations based on single and pooled populations, respectively, and can be queried in the SNPxGE(2) database via either gene symbol or reference SNP ID. For each reported association, a detailed information page is provided. AVAILABILITY: http://lambchop.ads.uga.edu/snpxge2/index.php CONTACT: wyp1125@uga.edu, rrekaya@uga.edu.


Subject(s)
Databases, Genetic , Polymorphism, Single Nucleotide , Disease/genetics , Gene Expression Profiling , Genetics, Medical , HapMap Project , Humans , Oligonucleotide Array Sequence Analysis
14.
BMC Genet ; 14: 124, 2013 Dec 26.
Article in English | MEDLINE | ID: mdl-24369108

ABSTRACT

BACKGROUND: Misclassification has been shown to have a high prevalence in binary responses in both livestock and human populations. Leaving these errors uncorrected before analyses will have a negative impact on the overall goal of genome-wide association studies (GWAS) including reducing predictive power. A liability threshold model that contemplates misclassification was developed to assess the effects of mis-diagnostic errors on GWAS. Four simulated scenarios of case-control datasets were generated. Each dataset consisted of 2000 individuals and was analyzed with varying odds ratios of the influential SNPs and misclassification rates of 5% and 10%. RESULTS: Analyses of binary responses subject to misclassification resulted in underestimation of influential SNPs and failed to estimate the true magnitude and direction of the effects. Once the misclassification algorithm was applied there was a 12% to 29% increase in accuracy, and a substantial reduction in bias. The proposed method was able to capture the majority of the most significant SNPs that were not identified in the analysis of the misclassified data. In fact, in one of the simulation scenarios, 33% of the influential SNPs were not identified using the misclassified data, compared with the analysis using the data without misclassification. However, using the proposed method, only 13% were not identified. Furthermore, the proposed method was able to identify with high probability a large portion of the truly misclassified observations. CONCLUSIONS: The proposed model provides a statistical tool to correct or at least attenuate the negative effects of misclassified binary responses in GWAS. Across different levels of misclassification probability as well as odds ratios of significant SNPs, the model proved to be robust. In fact, SNP effects, and misclassification probability were accurately estimated and the truly misclassified observations were identified with high probabilities compared to non-misclassified responses. This study was limited to situations where the misclassification probability was assumed to be the same in cases and controls which is not always the case based on real human disease data. Thus, it is of interest to evaluate the performance of the proposed model in that situation which is the current focus of our research.


Subject(s)
Genome-Wide Association Study , Algorithms , Humans , Odds Ratio , Phenotype , Polymorphism, Single Nucleotide , Probability
15.
Poult Sci ; 92(10): 2600-5, 2013 Oct.
Article in English | MEDLINE | ID: mdl-24046405

ABSTRACT

For 50 yr, residual feed intake (RFI) has remained a black box even though many researchers have touted it as a more biological estimate of efficiency of feed utilization than feed conversion ratio (FCR). We successfully dissected the efficiency of feed utilization by decomposing the components of RFI and ascertained the contributions of its components. Currently, a fixed effect model is used to predict RFI, which we term RFIF. We used a random effect model to predict RFIR, which allowed a separate estimation of RFI for maintenance (RFIM) and for growth (RFIG) and also ascertained their respective efficiencies. Judged by residual variance, R(2) and deviance information criterion, the random effect model was superior to the traditional fixed effect model used to generate RFIF. Under the traditional method, the h(2) of RFIF was 0.13 but h(2) of RFIR was 0.35. The heritability of RFIM and RFIG were moderate (~0.50), but the genetic correlation between them was highly negative (-0.95), suggesting that these 2 efficiencies contribute in an opposing way toward RFI. As a result, there should be caution in ascribing a biological basis to RFI. Under the current methodology, a biological basis can be ascribed to RFIM and RFIG. Selecting on RFIM will lead to smaller but efficient birds. The genetic gains in feed efficiency will be achieved by reductions in feed required for maintenance. The RFIG is not an efficiency parameter and should not be used as a sole criterion for selection. The ability of the current method to estimate efficiency values for metabolic BW and BW gain provides geneticists with additional parameters to use to discriminate between animals with similar RFIR. It also provides the flexibility to impose weights on RFIM and RFIG to meet a desired objective.


Subject(s)
Animal Husbandry/methods , Animal Nutritional Physiological Phenomena , Chickens/physiology , Eating , Animal Feed , Animals , Chickens/genetics , Female , Male , Models, Biological , Weight Gain
16.
Poult Sci ; 92(9): 2535-40, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23960139

ABSTRACT

Misclassification of dependent variables is a major issue in many areas of science that can arise when indirect markers are used to classify subjects or continuous traits are treated as categorical. In human medicine, this can have significant impacts on diagnostic accuracy. In animal science applications, misclassification can negatively affect both the accuracy of selection and the ability to ascertain the biological mechanisms for traits of interest. When dealing with traits influenced by genetic factors, genomic markers, such as SNP, can provide direct measurements of the underlying mechanisms controlling phenotypic responses. Unfortunately, in the presence of misclassification in the discrete dependent variables, the robustness of the analysis and the validity of the results could be severely compromised. To quantify the impact of misclassification on genome-wide association studies for binary responses, a real databased simulation was carried out. The simulated data consisted of 2,400 animals genotyped for 50K SNP. A binary trait with heritability equal to 0.10 and prevalence of 20% was generated. A rate of 1, 5, and 10% misclassification was artificially introduced to the true binary responses. Using a latent-threshold model, 3 analyses were carried out for each misclassification rate using 1) the true data (M1), 2) the contaminated data and ignoring misclassification (M2), and 3) the contaminated data and accounting for misclassification (M3). The results indicate that ignoring misclassification, when it exists in the data such as in M2, will lead to major deterioration in the performance of the model. When misclassification was contemplated in the model (M2), the results indicated a strong capacity of the procedure in dealing with potential misclassification in the training set. In fact, a large portion of miscoded samples in the training set was identified and corrected. The results of this study suggest that the proposed method is adequate and effective for practical genome-wide association studies for binary response classification.


Subject(s)
Computer Simulation , Genome-Wide Association Study/methods , Polymorphism, Single Nucleotide , Poultry/genetics , Animals , Models, Genetic , Research Design
17.
Poult Sci ; 102(10): 102993, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37611453

ABSTRACT

Heavy selection for growth in turkeys has led to a decay in leg soundness and walking ability. In this study, different models and traits were used to investigate the genetic relationships between body weight (BW) and walking ability (WA) in a turkey population. The data consisted of BW and WA traits collected on 276,059 male birds. Body weight was measured at 12 and 20 wk and WA at 20 wk of age. For WA, birds were scored based on a 1 (bad) to 6 (good) grading system. Due to the small number of records with scores 5 and 6, birds with WA scores of 4, 5, and 6 were grouped together resulting in only 4 classes. Additionally, a binary classification of WA (scores 1 and 2 = Similarly, an estimate of the genetic correlation between WA and BW at 20 wk was -0.45, indicating a more pronounced class 1; scores 3, 4, 5, and 6 = class 2) was evaluated. The inheritability estimates of WA ranged between 0.25 and 0.27 depending on the number of classes. The Heritability of BW at 12 and 20 wk was 0.44 and 0.51, respectively. The genetic correlation between WA and BW at 12 wk was around -0.35, indicating that heavy birds tend to have poor WA. antagonistic relationship between BW and WA. The genetic correlation between BW at 12 and 20 wk was positive and high (0.80). The residual correlation between WA and BW at 12 and 20 wk of age was -0.07 and -0.02, respectively. The residual correlation between body weight traits was 0.57. Similar results were observed when a binary classification was adopted for WA. The probability of an individual with a given genetic merit expressing a certain class of WA was determined for different fixed effect designations. Predictive probabilities clearly showed that birds when hatched in the winter would have a small chance to exhibit good WA phenotypes.


Subject(s)
Chickens , Turkeys , Male , Animals , Turkeys/physiology , Body Weight/genetics , Linear Models , Walking
18.
Animals (Basel) ; 13(18)2023 Sep 20.
Article in English | MEDLINE | ID: mdl-37760379

ABSTRACT

The aim of this study was to investigate the potential non-linear relationship between growth and walking ability (WA). The phenotypic data included body weights at 12 and 20 weeks and WA at 20 weeks of age measured on 276,059 male turkeys. The growth rate at three age periods (0 to 12, 12 to 20 and 0 to 20 weeks) was calculated. Each bird was assigned to one of the quartiles of the growth rate distribution for each age period. Between the first and fourth quartiles, the incidence of score 1 (bad WA) increased by 31, 18, and 33% for the first, second, and third age periods, respectively. For good WA (scores 4, 5, and 6), the incidence decreased by 55, 66, and 72% between the first and fourth quartiles for the first, second, and third age periods, respectively. Estimates of heritability of WA ranged between 0.18 and 0.26. The genetic correlations between adjacent growth rate quartiles were high and decayed as the interval between quartiles increased. The magnitude of the variation in the incidence of walking scores and genetic correlations across the growth rate quartiles point towards a non-linear relationship between growth and mobility suggesting other factors may affect walking ability.

19.
Animals (Basel) ; 13(18)2023 Sep 14.
Article in English | MEDLINE | ID: mdl-37760311

ABSTRACT

Glucose level in birds' tissue decreases due to heat stress (HS)-induced reduction in feed intake (FI); impairing metabolism and growth. The effect of glucose supplementation on the performance of broiler chickens was evaluated under thermoneutral (TN) and HS conditions. Glucose was supplemented at 0 and 6% under TN-(25 °C) and HS-(25 °C-35 °C-25 °C) conditions. The treatments were TN + 0%-glucose (TN0); TN + 6%-glucose (TN6), HS + 0%-glucose (HS0) and HS + 6%-glucose (HS6). There were 6 replicates (19 birds each)/treatment. Heat and glucose supplementation were applied from d28-35. At d35, Pectoralis (P.) major was sampled from one bird/replicate to determine glucose transporters' mRNA expression. Heat application lowered (p < 0.05) FI, body weight gain, and increased feed and water conversion ratios. Glucose supplementation increased total energy intake by 4.9 and 3.2% in TN and HS groups, respectively but reduced FI under TN and HS conditions. The P. major- and drumstick-yield reduced (p < 0.05) in HS0 compared to TN0, TN6 and HS6. Under HS, glucose supplementation improved eviscerated carcass weight by 9% and P. major yield by 14%. Glucose supplementation increased SGLT1 expression with/without heat treatment while HS independently increased the expression of GLUT 1, 5 and 10. Glucose supplementation under HS could improve performance of broilers.

20.
Poult Sci ; 102(11): 102973, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37633082

ABSTRACT

Even though water is the most essential nutrient for poultry production, adequate data on individual water intake in broiler chickens and its relationship with other traits of economic importance is scant. Water is provided to chickens in an unrestricted manner in spite of being a finite resource. Climate change continues to affect water sources and efficient bird use of water is long overdue. Understanding the biological basis of water intake is essential for sustainability of the poultry industry. Individual water and feed intake, and growth data was collected on 520 commercial broilers aged 14 to 42 days. We introduced the concepts of water conversion ratio (WCR) and residual water intake (RWI) as parameters that can be used to assess water intake efficiency. Water conversion ratio was defined as the amount of water consumed per unit of body weight gain, and RWI was defined as the difference between the actual water intake (WI) of a given bird and the expected WI by an average bird from the population with the same metabolic body weight, feed intake (FI) and body weight gain (BWG). The correlation between WI and FI was positive (r=0.77; P<0.0001), and the correlation between WI and BWG was positive (r=0.80; P<0.0001). Based on the distribution of RWI, the bottom 5 birds (LRWI) and the top 5 birds (HRWI) for RWI were selected for mRNA expression differences. The average broiler consumed about 7.8 L (± 1L) of water from 14 to 42 days of age. The mRNA expression of arginine vasopressin (AVP) antidiuretic hormone, calcium sensing receptor (CasR), sodium channel epithelial 1 subunit alpha (SCNN1A) and SCNN1D in the hypothalamus was upregulated in the LRWI group compared to the HRWI group. Similarly, kidney aquaporins (AQP) 2, 3, and 4 were upregulated in the LRWI group compared with the HRWI group. Given that water was provided ad libitum, the up-regulation of AVP and AQP gene mRNA expressions seem to indicate that the LRWI birds were more efficient in water reabsorption in the kidney compared to their HRWI counterparts. Increased water reabsorption will reduce the amount of water consumed to attain hydration. The water reabsorption potential was reflected in the excreta moisture levels as the LRWI birds had significantly lower excreta moisture than the HRWI birds. Excreta moisture level require further studies and could be considered as a potential proxy trait for water intake.


Subject(s)
Chickens , Drinking , Animals , Chickens/physiology , Poultry , Body Weight , Weight Gain/physiology , Water , RNA, Messenger , Animal Feed/analysis , Diet/veterinary
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