scholarly journals Comparison of granddaughter design and general pedigree design analysis of QTL in dairy cattle: a simulation study

2011 ◽  
Vol 50 (No. 12) ◽  
pp. 545-552 ◽  
Author(s):  
G. Freyer ◽  
N. Vukasinovic
Keyword(s):  
Dairy Cattle ◽  
Variance Component Model ◽  
Polygenic Effect ◽  
Relationship Matrix ◽  
Variance Matrix ◽  
General Pedigree ◽  
Identical By Descent ◽  
Complex Pedigree ◽  
Higher Power ◽  
Daughter Design

Traditional methods for detection and mapping of quantitative trait loci (QTL) in dairy cattle populations are usually based on daughter design (DD) or granddaughter design (GDD). Although these designs are well established and usually successful in detecting QTL, they consider sire families independently of each other, thereby ignoring relationships among other animals in the population and consequently, reducing the power of QTL detection. In this study we compared a traditional GDD with a general pedigree design (GPD) and assessed the precision and power of both methods for detecting and locating QTL in a simulated complex pedigree. QTL analyses were performed under the variance component model containing a random QTL and a random polygenic effect. The covariance matrix of the polygenic effect was a standard additive relationship matrix. The (co)variance matrix of the random QTL effect contained probabilities that QTL alleles shared by two individuals were identical by descent (IBD). In the GDD analysis, IBD probabilities were calculated using sires’ and daughters’ marker genotypes. In the GPD analysis, IBD probabilities were obtained using a deterministic approach. The estimation of QTL position and variance components was conducted using REML algorithm. Although both methods were able to locate the region of the QTL properly, the GPD method showed better precision of QTL position estimates in most cases and significantly higher power than the GDD method.  

scholarly journals On the use of whole-genome sequence data for across-breed genomic prediction and fine-scale mapping of QTL

2021 ◽  
Vol 53 (1) ◽  
Author(s):  
Theo Meuwissen ◽  
Irene van den Berg ◽  
Mike Goddard
Keyword(s):  
Variable Selection ◽  
Genome Sequence ◽  
Genomic Prediction ◽  
Milk Fat ◽  
Genotype Imputation ◽  
Whole Genome Sequence ◽  
Genomic Relationship Matrix ◽  
Polygenic Effect ◽  
Relationship Matrix ◽  
Whole Genome

Abstract Background Whole-genome sequence (WGS) data are increasingly available on large numbers of individuals in animal and plant breeding and in human genetics through second-generation resequencing technologies, 1000 genomes projects, and large-scale genotype imputation from lower marker densities. Here, we present a computationally fast implementation of a variable selection genomic prediction method, that could handle WGS data on more than 35,000 individuals, test its accuracy for across-breed predictions and assess its quantitative trait locus (QTL) mapping precision. Methods The Monte Carlo Markov chain (MCMC) variable selection model (Bayes GC) fits simultaneously a genomic best linear unbiased prediction (GBLUP) term, i.e. a polygenic effect whose correlations are described by a genomic relationship matrix (G), and a Bayes C term, i.e. a set of single nucleotide polymorphisms (SNPs) with large effects selected by the model. Computational speed is improved by a Metropolis–Hastings sampling that directs computations to the SNPs, which are, a priori, most likely to be included into the model. Speed is also improved by running many relatively short MCMC chains. Memory requirements are reduced by storing the genotype matrix in binary form. The model was tested on a WGS dataset containing Holstein, Jersey and Australian Red cattle. The data contained 4,809,520 genotypes on 35,549 individuals together with their milk, fat and protein yields, and fat and protein percentage traits. Results The prediction accuracies of the Jersey individuals improved by 1.5% when using across-breed GBLUP compared to within-breed predictions. Using WGS instead of 600 k SNP-chip data yielded on average a 3% accuracy improvement for Australian Red cows. QTL were fine-mapped by locating the SNP with the highest posterior probability of being included in the model. Various QTL known from the literature were rediscovered, and a new SNP affecting milk production was discovered on chromosome 20 at 34.501126 Mb. Due to the high mapping precision, it was clear that many of the discovered QTL were the same across the five dairy traits. Conclusions Across-breed Bayes GC genomic prediction improved prediction accuracies compared to GBLUP. The combination of across-breed WGS data and Bayesian genomic prediction proved remarkably effective for the fine-mapping of QTL.

scholarly journals 330 A hybrid model for genomic selection using prioritized SNPs based on FST scores in the presence of non-genotyped animals

2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 51-51
Author(s):  
Sajjad Toghiani ◽  
Ling-Yun Chang ◽  
El H Hay ◽  
Andrew J Roberts ◽  
Samuel E Aggrey ◽  
...  
Keyword(s):  
Genomic Selection ◽  
Hybrid Approach ◽  
Computational Cost ◽  
Simulated Data ◽  
Snp Markers ◽  
Genomic Relationship Matrix ◽  
Polygenic Effect ◽  
Relationship Matrix ◽  
Continuous Increase ◽  
Missing Genotypes

Abstract The dramatic advancement in genotyping technology has greatly reduced the complexity and cost of genotyping. The continuous increase in the density of marker panels is resulting in little to no improvement in the accuracy of genomic selection. Direct inversion of the genomic relationship matrix is infeasible for some livestock populations due to the excessive computational cost. In addition, most animals in genetic evaluation programs are non-genotyped. Including these animals in a genomic evaluation requires the imputation of the missing genotypes when using regression methods. To overcome these challenges, a hybrid approach is proposed. This approach fits a subset of SNP markers selected based on FST scores and a classical polygenic effect. The method was first tested using only genotyped animals and then extended to accommodate non-genotyped animals. The proposed approach was evaluated using simulated data for a trait with heritability of 0.1 and 0.4 and weaning weight in a crossbred beef cattle population. When all animals were genotyped, the hybrid approach using only 2.5% of prioritized SNPs exceeded the prediction accuracies of BayesB, BayesC, and GBLUP by more than 7%. When non-genotyped animals were incorporated, the proposed approach significantly outperformed ss-GBLUP method in terms of prediction accuracy under both simulated heritability scenarios. Although the results seem to depend on the genetic complexity of the trait, the proposed approach resulted in higher prediction accuracies than current methods. Furthermore, its computational costs in terms of CPU time and peak memory are substantially lower than the current methods.

scholarly journals On the Estimation of Heritability with Family-Based and Population-Based Samples

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Youngdoe Kim ◽  
Young Lee ◽  
Sungyoung Lee ◽  
Nam Hee Kim ◽  
Jeongmin Lim ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Large Scale ◽  
Density Lipoprotein ◽  
Population Based ◽  
Variance Component Analysis ◽  
Polygenic Effect ◽  
Relationship Matrix ◽  
Phenotypic Variance ◽  
Heritability Estimates ◽  
Family Based

For a family-based sample, the phenotypic variance-covariance matrix can be parameterized to include the variance of a polygenic effect that has then been estimated using a variance component analysis. However, with the advent of large-scale genomic data, the genetic relationship matrix (GRM) can be estimated and can be utilized to parameterize the variance of a polygenic effect for population-based samples. Therefore narrow sense heritability, which is both population and trait specific, can be estimated with both population- and family-based samples. In this study we estimate heritability from both family-based and population-based samples, collected in Korea, and the heritability estimates from the pooled samples were, for height, 0.60; body mass index (BMI), 0.32; log-transformed triglycerides (log TG), 0.24; total cholesterol (TCHL), 0.30; high-density lipoprotein (HDL), 0.38; low-density lipoprotein (LDL), 0.29; systolic blood pressure (SBP), 0.23; and diastolic blood pressure (DBP), 0.24. Furthermore, we found differences in how heritability is estimated—in particular the amount of variance attributable to common environment in twins can be substantial—which indicates heritability estimates should be interpreted with caution.

scholarly journals 334 Investigating core-dependent changes in predictions using the algorithm for proven and young in ssGBLUP

2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 50-50
Author(s):  
Daniela Lourenco ◽  
Shogo Tsuruta ◽  
Ivan Pocrnic ◽  
Ignacy Misztal
Keyword(s):  
Dairy Cattle ◽  
Large Scale ◽  
Growth Traits ◽  
Optimal Number ◽  
Single Step ◽  
Eigenvalue Decomposition ◽  
Genomic Relationship Matrix ◽  
Relationship Matrix ◽  
Direct Inversion ◽  
Lower Accuracy

Abstract Large-scale single-step GBLUP (ssGBLUP) evaluations rely on techniques to approximate or avoid the inversion of the genomic relationship matrix (G). The algorithm for proven and young (APY) was developed to create the inverse of G without explicit inversion, and relies on the clustering of genotyped animals into two groups, namely core and non-core. Although the correlation between GEBV from regular ssGBLUP and APY ssGBLUP is greater than 0.99 when the appropriate number of core animals is used, reranking is still observed when different core groups are used. We investigated which animals are more suitable to reranking and how the changes in GEBV can be minimized. Datasets from beef and dairy cattle, and pigs were used. The beef cattle data comprised phenotypes on 3 growth traits for up to 6.8M animals, pedigree for 8.2M, and genotypes for 66k. A dairy cattle data with 9M phenotypes for udder depth, 10M animals in pedigree, and 570K genotyped was used. The pig dataset had up to 770k phenotypes recorded on 4 traits, pedigree for 2.6M animals and genotypes for 54k. Investigations included using several different core groups, increasing the number of core animals beyond the optimal number obtained by the eigenvalue decomposition, and comparisons with GEBV from ssGBLUP with direct inversion (except for dairy). Additionally, observed changes were compared with possible changes based on SE of GEBV. In all datasets, larger changes in GEBV by using different core groups were observed for animals with lower accuracy. The observed changes relative to standard deviations of GEBV were, on average, 5% and ranged from 0 to 30%. Increasing the number of core animals beyond the optimal value helped to asymptotically reduce changes in GEBV. Although core-dependent changes in GEBV exist, they are small and can be reduced with larger core groups.

scholarly journals 10 Can single-step genome-wide association analysis (ssGWAA) account for population structure?

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 9-10
Author(s):  
Enrico Mancin
Keyword(s):  
Population Structure ◽  
Beef Cattle ◽  
Dairy Cattle ◽  
Association Analysis ◽  
Single Step ◽  
Genome Wide Association ◽  
Relationship Matrix ◽  
Cattle Population ◽  
Genome Wide Association Analysis ◽  
Genome Wide

Abstract Several methods are available for genome-wide association analysis, including the classical GWAA (cGWAA) based on fixed, single-SNP regression; efficient mixed-model association expedited (EMMAX) that fits single-SNP regressions together with a relationship matrix to account for population structure; and single-step GWAA (ssGWAA) where all data, including non-genotyped animals, are used. The objectives of this study were to: 1) investigate the ability of ssGWAA to account for population structure and correctly identify quantitative trait nucleotides (QTN); and 2) compare ssGWAA with cGWAA and EMMAX. Three simulated datasets were used, which mimic fish, beef cattle, and dairy cattle populations. The fish population was composed of 2,040 fish, out of which 1,040 were genotyped and had phenotypes for a trait with heritability of 0.25. The beef cattle population had 6,010 animals in the pedigree, but only 1,500 with phenotypes (h2 = 0.35) and genotypes. Lastly, the dairy cattle population had 40,800 pedigreed animals, of which 20,000 females had phenotypes (h2 = 0.32) and 2,400 males were genotyped. All phenotypes, pedigree, and genotypes were used in ssGWAA, whereas only genotypes and phenotypes were used in cGWAA and EMMAX for the fish and beef cattle analyses. For the dairy cattle analysis using the last two methods, deregressed proofs had to be used instead of phenotypes. The ability to correctly identify QTN and the number of statistically significant SNP (P < 0.05/number of SNP) was assessed among methods. In all populations, cGWAA was able to identify some of the strongest QTN but showed a large number of false positives. EMMAX and ssGWAA did not show false associations and correctly identified the top QTN, with more signals observed in ssGWAA. The ssGWAA accounts for population structure and is a proper association method, especially for livestock populations where sparse genotyping is a reality and phenotypes may not be recorded in genotyped animals.

scholarly journals Importance of correcting genomic relationships in single-locus QTL mapping model with an Advanced Backcross population

2021 ◽  
Author(s):  
Boby Mathew ◽  
Jens Léon ◽  
Said Dadshani ◽  
Klaus Pillen ◽  
Mikko J Sillanpää ◽  
...  
Keyword(s):  
Qtl Mapping ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Allele Frequencies ◽  
Genomic Relationship Matrix ◽  
Polygenic Effect ◽  
Relationship Matrix ◽  
Mendelian Segregation ◽  
Backcross Population ◽  
Advanced Backcross

Abstract Advanced Backcross (AB) populations have been widely used to identify and utilize beneficial alleles in various crops such as rice, tomato, wheat and barley. For the development of an AB population, a controlled crossing scheme is used and this controlled crossing along with the selection (both natural and artificial) of agronomically-adapted alleles during the development of AB population may lead to unbalanced allele frequencies in the population. However, it is commonly believed that interval mapping mapping of traits in experimental crosses such as AB populations are immune to the deviations from the expected frequencies under Mendelian segregation. Using two AB populations and simulated data sets as examples, we describe the severity of the problem caused by unbalanced allele frequencies in quantitative trait loci (QTL) mapping and demonstrate how it can be corrected using the linear mixed model having a polygenic effect with the covariance structure (genomic relationship matrix) calculated from molecular markers.

scholarly journals Determination of Allele Frequencies for Quantitative Trait Loci in Commercial Animal Populations

2005 ◽  
Author(s):  
Joel I. Weller ◽  
Harris A. Lewin ◽  
Micha Ron
Keyword(s):  
Mammary Gland ◽  
Dairy Cattle ◽  
Single Gene ◽  
Allele Frequencies ◽  
Causative Mutation ◽  
Economic Traits ◽  
Allelic Frequencies ◽  
Animal Populations ◽  
Israeli Population ◽  
Daughter Design

Individual loci affecting economic traits in dairy cattle (ETL) have been detected via linkage to genetic markers by application of the granddaughter design in the US population and the daughter design in the Israeli population. From these analyses it is not possible to determine allelic frequencies in the population at large, or whether the same alleles are segregating in different families. We proposed to answer this question by application of the "modified granddaughter design", in which granddaughters with a common maternal grandsire are both genotyped and analyzed for the economic traits. The objectives of the proposal were: 1) to fine map three segregating ETL previously detected by a daughter design analysis of the Israeli dairy cattle population; 2) to determine the effects of ETL alleles in different families relative to the population mean; 3) for each ETL, to determine the number of alleles and allele frequencies. The ETL on Bostaurusautosome (BT A) 6 chiefly affecting protein concentration was localized to a 4 cM chromosomal segment centered on the microsatellite BM143 by the daughter design. The modified granddaughter design was applied to a single family. The frequency of the allele increasing protein percent was estimated at 0.63+0.06. The hypothesis of equal allelic frequencies was rejected at p<0.05. Segregation of this ETL in the Israeli population was confirmed. The genes IBSP, SPP1, and LAP3 located adjacent to BM143 in the whole genome cattle- human comparative map were used as anchors for the human genome sequence and bovine BAC clones. Fifteen genes within 2 cM upstream of BM143 were located in the orthologous syntenic groups on HSA4q22 and HSA4p15. Only a single gene, SLIT2, was located within 2 cM downstream of BM143 in the orthologous HSA4p15 region. The order of these genes, as derived from physical mapping of BAC end sequences, was identical to the order within the orthologous syntenic groups on HSA4: FAM13A1, HERC3. CEB1, FLJ20637, PP2C-like, ABCG2, PKD2. SPP, MEP, IBSP, LAP3, EG1. KIAA1276, HCAPG, MLR1, BM143, and SLIT2. Four hundred and twenty AI bulls with genetic evaluations were genotyped for 12 SNPs identified in 10 of these genes, and for BM143. Seven SNPs displayed highly significant linkage disequilibrium effects on protein percentage (P<0.000l) with the greatest effect for SPP1. None of SNP genotypes for two sires heterozygous for the ETL, and six sires homozygous for the ETL completely corresponded to the causative mutation. The expression of SPP 1 and ABCG2 in the mammary gland corresponded to the lactation curve, as determined by microarray and QPCR assays, but not in the liver. Anti-sense SPP1 transgenic mice displayed abnormal mammary gland differentiation and milk secretion. Thus SPP 1 is a prime candidate gene for this ETL. We confirmed that DGAT1 is the ETL segregating on BTA 14 that chiefly effects fat concentration, and that the polymorphism is due to a missense mutation in an exon. Four hundred Israeli Holstein bulls were genotyped for this polymorphism, and the change in allelic frequency over the last 20 years was monitored.   

A simple method of pedigree evaluation in dairy cattle

1959 ◽  
Vol 1 (2) ◽  
pp. 167-174 ◽  
Author(s):  
Alan Robertson
Keyword(s):  
Dairy Cattle ◽  
Approximate Method ◽  
Simple Method ◽  
Loss Of Information ◽  
Equivalent Number ◽  
Complex Pedigree

A simple but approximate method of pedigree evaluation is presented with particular reference to dairy cattle. It involves the expression of information available on any animal in the pedigree in terms of the equivalent number of ‘standard progeny records’. Formulae are given for the transfer of evidence from generation to generation within the pedigree. The application to one rather complex pedigree is illustrated and it is shown that the loss of information through the approximation is small.

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