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Durum wheat is an important crop for the human diet and its consumption is gaining popularity. In order to ensure that durum wheat production maintains the pace with the increase in demand, it is necessary to raise productivity by approximately 1.5% per year. To deliver this level of annual genetic gain the incorporation of molecular strategies has been proposed as a key solution. Here, four RILs populations were used to conduct QTL discovery for grain yield (GY) and 1,000 kernel weight (TKW). A total of 576 individuals were sown at three locations in Morocco and one in Lebanon. These individuals were genotyped by sequencing with 3,202 high-confidence polymorphic markers, to derive a consensus genetic map of 2,705.7 cM, which was used to impute any missing data. Six QTLs were found to be associated with GY and independent from flowering time on chromosomes 2B, 4A, 5B, 7A and 7B, explaining a phenotypic variation (PV) ranging from 4.3 to 13.4%. The same populations were used to train genomic prediction models incorporating the relationship matrix, the genotype by environment interaction, and marker by environment interaction, to reveal significant advantages for models incorporating the marker effect. Using training populations (TP) in full sibs relationships with the validation population (VP) was shown to be the only effective strategy, with accuracies reaching 0.35–0.47 for GY. Reducing the number of markers to 10% of the whole set, and the TP size to 20% resulted in non-significant changes in accuracies. The QTLs identified were also incorporated in the models as fixed effects, showing significant accuracy gain for all four populations. Our results confirm that the prediction accuracy depends considerably on the relatedness between TP and VP, but not on the number of markers and size of TP used. Furthermore, feeding the model with information on markers associated with QTLs increased the overall accuracy. [ABSTRACT FROM AUTHOR]

The cultivated strawberry, Fragaria ×ananassa, is a recently domesticated fruit species of economic interest worldwide. As such, there is significant interest in continuous varietal improvement. Genomics-assisted improvement, including the use of DNA markers and genomic selection have facilitated significant improvements of numerous key traits during strawberry breeding. CRISPR/Cas-mediated genome editing allows targeted mutations and precision nucleotide substitutions in the target genome, revolutionizing functional genomics and crop improvement. Genome editing is beginning to gain traction in the more challenging polyploid crops, including allo-octoploid strawberry. The release of high-quality reference genomes and comprehensive subgenome-specific genotyping and gene expression profiling data in octoploid strawberry will lead to a surge in trait discovery and modification by using CRISPR/Cas. Genome editing has already been successfully applied for modification of several strawberry genes, including anthocyanin content, fruit firmness and tolerance to post-harvest disease. However, reports on many other important breeding characteristics associated with fruit quality and production are still lacking, indicating a need for streamlined genome editing approaches and tools in Fragaria ×ananassa. In this review, we present an overview of the latest advancements in knowledge and breeding efforts involving CRISPR/Cas genome editing for the enhancement of strawberry varieties. Furthermore, we explore potential applications of this technology for improving other Rosaceous plant species. [ABSTRACT FROM AUTHOR]

Common bean (bean) is one of the most important legume crops, and mapping genes for yield and yield-related traits is essential for its improvement. However, yield is a complex trait that is typically controlled by many loci in crop genomes. The objective of this research was to identify regions in the bean genome associated with yield and a number of yield-related traits using a collection of 121 diverse bean genotypes with different yields. The beans were evaluated in replicated trials at two locations, over two years. Significant variation among genotypes was identified for all traits analyzed in the four environments. The collection was genotyped with the BARCBean6K_3 chip (5,398 SNPs), two yield/ antiyield gene-based markers, and seven markers previously associated with resistance to common bacterial blight (CBB), including a Niemann–Pick polymorphism (NPP) gene-based marker. Over 90% of the single-nucleotide polymorphisms (SNPs) were polymorphic and separated the panel into two main groups of small-seeded and large-seeded beans, reflecting their Mesoamerican and Andean origins. Thirty-nine significant marker-trait associations (MTAs) were identified between 31 SNPs and 15 analyzed traits on all 11 bean chromosomes. Some of these MTAs confirmed genome regions previously associated with the yield and yield-related traits in bean, but a number of associations were not reported previously, especially those with derived traits. Over 600 candidate genes with different functional annotations were identified for the analyzed traits in the 200-Kb region centered on significant SNPs. Fourteen SNPs were identified within the gene model sequences, and five additional SNPs significantly associated with five different traits were located at less than 0.6 Kb from the candidate genes. The work confirmed associations between two yield/antiyield gene-based markers (AYD1m and AYD2m) on chromosome Pv09 with yield and identified their association with a number of yield-related traits, including seed weight. The results also confirmed the usefulness of the NPP marker in screening for CBB resistance. Since disease resistance and yield measurements are environmentally dependent and laborintensive, the three gene-based markers (CBB- and two yield-related) and quantitative trait loci (QTL) that were validated in this work may be useful tools for simplifying and accelerating the selection of high-yielding and CBB-resistant bean cultivars. [ABSTRACT FROM AUTHOR]

The parasitic weed, Striga is amajor biological constraint to cereal production in sub-Saharan Africa (SSA) and threatens food and nutrition security. Two hundred and twenty-three (223) F2:3 mapping population involving individuals derived from TZdEI 352 x TZEI 916 were phenotyped for four Striga-adaptive traits and genotyped using the Diversity Arrays Technology (DArT) to determine the genomic regions responsible for Striga resistance in maize. After removing distorted SNP markers, a genetic linkage map was constructed using 1,918 DArTseq markers which covered 2092.1 cM. Using the inclusive composite interval mapping method in IciMapping, twenty-three QTLs influencing Striga resistance traits were identified across four Striga-infested environments with five stable QTLs (qGY4, qSC2.1, qSC2.2, qSC5, and qSC6) detected inmore than one environment. The variations explained by the QTLs ranged from4.1% (qSD2.3) to 14.4% (qSC7.1). SixQTLs each with significant additive x environment interactionswere also identified for grain yield and Striga damage. Gene annotation revealed candidate genes underlying the QTLs, including the gene models GRMZM2G077002 and GRMZM2G404973 which encode the GATA transcription factors, GRMZM2G178998 and GRMZM2G134073 encoding the NAC transcription factors, GRMZM2G053868 and GRMZM2G157068 which encode the nitrate transporter protein and GRMZM2G371033 encoding the SBP-transcription factor. These candidate genes play crucial roles in plant growth and developmental processes and defense functions. This study provides further insights into the genetic mechanisms of resistance to Striga parasitism in maize. The QTL detected in more than one environment would be useful for further fine-mapping andmarker-assisted selection for the development of Striga resistant and high-yielding maize cultivars. [ABSTRACT FROM AUTHOR]

Fusarium head blight (FHB) of wheat is an important disease worldwide, affecting the yield, end-use quality and threatening food safety. Genetic resources or stable loci for FHB resistance are still limited in breeding programs. A panel of 265 bread wheat accessions from China, CIMMYTMexico and other countries was screened for FHB resistance under 5 field experiments in Mexico and China, and a genome-wide association analysis was performed to identify QTLs associated with FHB resistance. The major locus Fhb1 was significantly associated with FHB severity and Deoxynivalenol content in grains. FHB screening experiments in multiple environments showed that Fhb1-harbouring accessions Sumai3, Sumai5, Ningmai9, Yangmai18 and Tokai66 had low FHB index, disease severity and DON content in grains in response to different Fusarium species and ecological conditions in Mexico and China. Accessions Klein Don Enrique, Chuko and Yumai34 did not have Fhb1 but still showed good FHB resistance and low mycotoxin accumulation. Sixteen loci associated with FHB resistance or DON content in grains were identified on chromosomes 1A, 1B, 2B, 3A, 3D, 4B, 4D, 5A, 5B, 7A, and 7B in multiple environments, explaining phenotypic variation of 4.43–10.49%. The sources with good FHB resistance reported here could be used in breeding programs for resistance improvement in Mexico and China, and the significant loci could be further studied and introgressed for resistance improvement against FHB and mycotoxin accumulation in grains. [ABSTRACT FROM AUTHOR]

Metagenomic predictions use variation in the metagenome (microbiome profile) to predict the unknown phenotype of the associated host. Metagenomic predictions were first developed 10 years ago, where they were used to predict which cattle would produce high or low levels of enteric methane. Since then, the approach has been applied to several traits and species including residual feed intake in cattle, and carcass traits, body mass index and disease state in pigs. Additionally, the method has been extended to include predictions based on other multi-dimensional data such as the metabolome, as well to combine genomic and metagenomic information. While there is still substantial optimisation required, the use of metagenomic predictions is expanding as DNA sequencing costs continue to fall and shows great promise particularly for traits heavily influenced by the microbiome such as feed efficiency and methane emissions. [ABSTRACT FROM AUTHOR]

Throughout the ages, the common bean has been consumed by humanity as an important food staple crop and source of nutrition on a global scale. Since its domestication, a wide spectrum of phenotypic and genotypic investigations have been carried out to unravel the potential of this crop and to understand the process of nutrient accumulation along with other desirable characteristics. The common bean is one of the essential legume crops due to its high protein and micronutrient content. The balance in micronutrients is critical for the growth and development of plants as well as humans. Iron (Fe), Zinc (Zn), Copper (Cu), Manganese (Mn), Magnesium (Mg), Calcium (Ca), and Molybdenum (Mo) are some of the important micronutrients present in legumes. Thus, we aimed to investigate the quantitative trait loci's (QTLs)/single nucleotide polymorphisms (SNPs) to identify the candidate genes associated with micronutrients through genotyping by sequencing (GBS). In our investigation, through GBS we identified SNPs linked with traits and assessed seven micronutrients in 96 selected common bean genotypes for screening nutritionally rich genotypes. Among 96399 SNPs total identified through GBS, 113 SNPs showed significant phenotypic variance, ranging from 13.50 to 21.74%. SNPs associated with most of the seed micronutrients (Mg, Mn, Fe, Ca, Cu) were found on chr3 & chr11 (Mg, Mn, Mo, Ca, Zn). The findings from this study could be used for haplotype-based selection of nutritionally rich genotypes and for marker-assisted genetic enhancement of the common bean. Further, the identified SNPs for candidate genes/transporters associated with micronutrient content may pave the way for the enrichment of seeds by employing genomics-assisted breeding programs. [ABSTRACT FROM AUTHOR]

Ricebean (Vigna umbellata) is a lesser known pulse with well-recognized potential. Recently, it has emerged as a legume with endowed nutritional potential because of high concentration of quality protein and other vital nutrients in its seeds. However, the genes and pathways involved in regulating seed development and size are not understood in this crop. In our study, we analyzed the transcriptome of two genotypes with contrasting grain size (IC426787: large seeded and IC552985: small seeded) at two different time points, namely, 5 and 10 days post-anthesis (DPA). The bold seeded genotype across the time points (B5_B10) revealed 6,928 differentially expressed genes (DEGs), whereas the small seeded genotype across the time point (S5_S10) contributed to 14,544 DEGs. We have also identified several candidate genes for seed development–related traits like seed size and 100-seed weight. On the basis of similarity search and domain analysis, some candidate genes (PHO1 , cytokinin dehydrogenase , A-type cytokinin, and ARR response negative regulator) related to 100-seed weight and seed size showed downregulation in the small seeded genotype. The MapMan and KEGG analysis confirmed that auxin and cytokinin pathways varied in both the contrasting genotypes and can therefore be the regulators of the seed size and other seed development–related traits in ricebeans. A total of 51 genes encoding SCF TIR1/AFB , Aux/IAA , ARFs , E3 ubiquitin transferase enzyme, and 26S proteasome showing distinct expression dynamics in bold and small genotypes were also identified. We have also validated randomly selected SSR markers in eight accessions of the Vigna species (V. umbellata : 6; Vigna radiata : 1; and Vigna mungo : 1). Cross-species transferability pattern of ricebean–derived SSR markers was higher in V. radiata (73.08%) than V. mungo (50%). To the best of our knowledge, this is the first transcriptomic study conducted in this crop to understand the molecular basis of any trait. It would provide us a comprehensive understanding of the complex transcriptome dynamics during the seed development and gene regulatory mechanism of the seed size determination in ricebeans. [ABSTRACT FROM AUTHOR]

Important associations were identified in both panels harboring important candidate genes with proven roles in plant defense including Glucan synthase-like protein, NAC domain protein, senescence-associated genes, MAC/Perforin domain-containing gene, and ethylene response factor 1. Abiotic stress, disease resistance, candidate genes, association mapping, gene editing, QTL mapping, genomic selection, crop improvement Keywords: abiotic stress; disease resistance; candidate genes; association mapping; QTL mapping; genomic selection; gene editing; crop improvement EN abiotic stress disease resistance candidate genes association mapping QTL mapping genomic selection gene editing crop improvement 1 6 6 11/26/21 20211123 NES 211123 Twenty first century agriculture faces many challenges including new emerging abiotic and biotic stresses and decreasing arable land. Breeding disease resistant wheat varieties is one of the most important subject areas of wheat research and wheat blast ( I Magnaporthe oryzae i pathotype I Triticum i ) is considered one of the most destructive diseases in South American and South Asian countries. [Extracted from the article]

Maize lethal necrosis (MLN) is a viral disease with a devastating effect on maize production. Developing and deploying improved varieties with resistance to the disease is important to effectively control MLN; however, little is known about the causal genes and molecular mechanism(s) underlying MLN resistance. Screening thousands of maize inbred lines revealed KS23-5 and KS23-6 as two of the most promising donors of MLN resistance alleles. KS23-5 and KS23-6 lines were earlier developed at the University of Hawaii, United States, on the basis of a source population constituted using germplasm from Kasetsart University, Thailand. Both linkage mapping and association mapping approaches were used to discover and validate genomic regions associated with MLN resistance. Selective genotyping of resistant and susceptible individuals within large F2 populations coupled with genome-wide association study identified a major-effect QTL (qMLN06_157) on chromosome 6 for MLN disease severity score and area under the disease progress curve values in all three F2 populations involving one of the KS23 lines as a parent. The major-effect QTL (qMLN06_157) is recessively inherited and explained 55%–70% of the phenotypic variation with an approximately 6 Mb confidence interval. Linkage mapping in three F3 populations and three F2 populations involving KS23-5 or KS23-6 as one of the parents confirmed the presence of this major-effect QTL on chromosome 6, demonstrating the efficacy of the KS23 allele at qMLN06.157 in varying populations. This QTL could not be identified in population that was not derived using KS23 lines. Validation of this QTL in six F2 populations with 20 SNPs closely linked with qMLN06.157 was further confirmed its consistent expression across populations and its recessive nature of inheritance. On the basis of the consistent and effective resistance afforded by the KS23 allele at qMLN06.157 , the QTL can be used in both marker-assisted forward breeding and marker-assisted backcrossing schemes to improve MLN resistance of breeding populations and key lines for eastern Africa. [ABSTRACT FROM AUTHOR]

Low-coverage whole genome sequencing is a low-cost genotyping technology. Combined with genotype imputation approaches, it is likely to become a critical component of cost-effective genomic selection programs in agricultural livestock. Here, we used the low-coverage sequence data of 617 Dezhou donkeys to investigate the performance of genotype imputation for low-coverage whole genome sequence data and genomic prediction based on the imputed genotype data. The specific aims were as follows: 1) to measure the accuracy of genotype imputation under different sequencing depths, sample sizes, minor allele frequency (MAF), and imputation pipelines and 2) to assess the accuracy of genomic prediction under different marker densities derived from the imputed sequence data, different strategies for constructing the genomic relationship matrixes, and single-vs. multi-trait models. We found that a high imputation accuracy (>0.95) can be achieved for sequence data with a sequencing depth as low as 1x and the number of sequenced individuals ≥400. For genomic prediction, the best performance was obtained by using a marker density of 410K and a G matrix constructed using expected marker dosages. Multi-trait genomic best linear unbiased prediction (GBLUP) performed better than single-trait GBLUP. Our study demonstrates that low-coverage whole genome sequencing would be a cost-effective approach for genomic prediction in Dezhou donkey. [ABSTRACT FROM AUTHOR]

Genomic prediction has been widely used in multiple areas and various genomic prediction methods have been developed. The majority of these methods, however, focus on statistical properties and ignore the abundant useful biological information like genome annotation or previously discovered causal variants. Therefore, to improve prediction performance, several methods have been developed to incorporate biological information into genomic prediction, mostly in single-trait analysis. A commonly used method to incorporate biological information is allocating molecular markers into different classes based on the biological information and assigning separate priors to molecular markers in different classes. It has been shown that such methods can achieve higher prediction accuracy than conventional methods in some circumstances. However, these methods mainly focus on single-trait analysis, and available priors of these methods are limited. Thus, in both single-trait and multiple-trait analysis, we propose the multi-class Bayesian Alphabet methods, in which multiple Bayesian Alphabet priors, including RR-BLUP, BayesA, BayesB, BayesCΠ, and Bayesian LASSO, can be used for markers allocated to different classes. The superior performance of the multi-class Bayesian Alphabet in genomic prediction is demonstrated using both real and simulated data. The software tool JWAS offers open-source routines to perform these analyses. [ABSTRACT FROM AUTHOR]

Colletotrichum crown rot (CCR) caused by Colletotrichum gloeosporioides is a serious threat to the cultivated strawberry (Fragaria × ananassa). Our previous study reported that a major locus, FaRCg1 , increases resistance. However, the genomic structure of FaRCg1 and potential candidate genes associated with the resistance remained unknown. Here, we performed comparative transcriptome analyses of resistant 'Florida Elyana' and susceptible 'Strawberry Festival' after infection and identified candidate genes potentially involved in resistance. In 'Florida Elyana', 6,099 genes were differentially expressed in response to C. gloeosporioides. Gene ontology analysis showed that the most upregulated genes were functionally associated with signaling pathways of plant defense responses. Three genes in the genomic region of FaRCg1 were highly upregulated: a von Willebrand Factor A domain-containing protein, a subtilisin-like protease, and a TIFY 11A-like protein. Subgenome-specific markers developed for the candidate genes were tested with a diverse panel of 219 accessions from University of Florida and North Carolina State University breeding programs. Significant and positive associations were found between the high-resolution melting (HRM) marker genotypes and CCR phenotypes. These newly developed subgenome-specific functional markers for FaRCg1 can facilitate development of resistant varieties through marker-assisted selection. [ABSTRACT FROM AUTHOR]

Genetic variants which affect complex traits (causal variants) are thought to be found in functional regions of the genome. Identifying causal variants would be useful for predicting complex trait phenotypes in dairy cows, however, functional regions are poorly annotated in the bovine genome. Functional regions can be identified on a genome-wide scale by assaying for post-translational modifications to histone proteins (histone modifications) and proteins interacting with the genome (e.g., transcription factors) using a method called Chromatin immunoprecipitation followed by sequencing (ChIP-seq). In this study ChIP-seq was performed to find functional regions in the bovine genome by assaying for four histone modifications (H3K4Me1, H3K4Me3, H3K27ac, and H3K27Me3) and one transcription factor (CTCF) in 6 tissues (heart, kidney, liver, lung, mammary and spleen) from 2 to 3 lactating dairy cows. Eighty-six ChIP-seq samples were generated in this study, identifying millions of functional regions in the bovine genome. Combinations of histone modifications and CTCF were found using ChromHMM and annotated by comparing with active and inactive genes across the genome. Functional marks differed between tissues highlighting areas which might be particularly important to tissue-specific regulation. Supporting the cis-regulatory role of functional regions, the read counts in some ChIP peaks correlated with nearby gene expression. The functional regions identified in this study were enriched for putative causal variants as seen in other species. Interestingly, regions which correlated with gene expression were particularly enriched for potential causal variants. This supports the hypothesis that complex traits are regulated by variants that alter gene expression. This study provides one of the largest ChIP-seq annotation resources in cattle including, for the first time, in the mammary gland of lactating cows. By linking regulatory regions to expression QTL and trait QTL we demonstrate a new strategy for identifying causal variants in cattle. [ABSTRACT FROM AUTHOR]

Improvement of prediction accuracy of estimated breeding values (EBVs) can lead to increased profitability for swine breeding companies. This study was performed to compare the accuracy of different popular genomic prediction methods and traditional best linear unbiased prediction (BLUP) for future performance of back-fat thickness (BFT), average daily gain (ADG), and loin muscle depth (LMD) in Canadian Duroc, Landrace, and Yorkshire swine breeds. In this study, 17,019 pigs were genotyped using Illumina 60K and Affymetrix 50K panels. After quality control and imputation steps, a total of 41,304, 48,580, and 49,102 single-nucleotide polymorphisms remained for Duroc (n = 6,649), Landrace (n = 5,362), and Yorkshire (n = 5,008) breeds, respectively. The breeding values of animals in the validation groups (n = 392–774) were predicted before performance test using BLUP, BayesC, BayesCπ, genomic BLUP (GBLUP), and single-step GBLUP (ssGBLUP) methods. The prediction accuracies were obtained using the correlation between the predicted breeding values and their deregressed EBVs (dEBVs) after performance test. The genomic prediction methods showed higher prediction accuracies than traditional BLUP for all scenarios. Although the accuracies of genomic prediction methods were not significantly (P > 0.05) different, ssGBLUP was the most accurate method for Duroc-ADG, Duroc-LMD, Landrace-BFT, Landrace-ADG, and Yorkshire-BFT scenarios, and BayesCπ was the most accurate method for Duroc-BFT, Landrace-LMD, and Yorkshire-ADG scenarios. Furthermore, BayesCπ method was the least biased method for Duroc-LMD, Landrace-BFT, Landrace-ADG, Yorkshire-BFT, and Yorkshire-ADG scenarios. Our findings can be beneficial for accelerating the genetic progress of BFT, ADG, and LMD in Canadian swine populations by selecting more accurate and unbiased genomic prediction methods. [ABSTRACT FROM AUTHOR]

Bayesian regression models are widely used in genomic prediction for various species. By introducing the global parameter τ, which can shrink marker effects to zero, and the local parameter λ k , which can allow markers with large effects to escape from the shrinkage, we developed two novel Bayesian models, named BayesHP and BayesHE. The BayesHP model uses Horseshoe+ prior, whereas the BayesHE model assumes local parameter λ k , after a half-t distribution with an unknown degree of freedom. The performances of BayesHP and BayesHE models were compared with three classical prediction models, including GBLUP, BayesA, and BayesB, and BayesU, which also applied global–local prior (Horseshoe prior). To assess model performances for traits with various genetic architectures, simulated data and real data in cattle (milk production, health, and type traits) and mice (type and growth traits) were analyzed. The results of simulation data analysis indicated that models based on global–local priors, including BayesU, BayesHP, and BayesHE, performed better in traits with higher heritability and fewer quantitative trait locus. The results of real data analysis showed that BayesHE was optimal or suboptimal for all traits, whereas BayesHP was not superior to other classical models. For BayesHE, its flexibility to estimate hyperparameter automatically allows the model to be more adaptable to a wider range of traits. The BayesHP model, however, tended to be suitable for traits having major/large quantitative trait locus, given its nature of the "U" type-like shrinkage pattern. Our results suggested that auto-estimate the degree of freedom (e.g., BayesHE) would be a better choice other than increasing the local parameter layers (e.g., BayesHP). In this study, we introduced the global–local prior with unknown hyperparameter to Bayesian regression models for genomic prediction, which can trigger further investigations on model development. [ABSTRACT FROM AUTHOR]

The observable phenotype is the manifestation of information that is passed along different organization levels (transcriptional, translational, and metabolic) of a biological system. The widespread use of various omic technologies (RNA-sequencing, metabolomics, etc.) has provided plant genetics and breeders with a wealth of information on pertinent intermediate molecular processes that may help explain variation in conventional traits such as yield, seed quality, and fitness, among others. A major challenge is effectively using these data to help predict the genetic merit of new, unobserved individuals for conventional agronomic traits. Trait-specific genomic relationship matrices (TGRMs) model the relationships between individuals using genome-wide markers (SNPs) and place greater emphasis on markers that most relevant to the trait compared to conventional genomic relationship matrices. Given that these approaches define relationships based on putative causal loci, it is expected that these approaches should improve predictions for related traits. In this study we evaluated the use of TGRMs to accommodate information on intermediate molecular phenotypes (referred to as endophenotypes) and to predict an agronomic trait, total lipid content, in oat seed. Nine fatty acids were quantified in a panel of 336 oat lines. Marker effects were estimated for each endophenotype, and were used to construct TGRMs. A multikernel TRGM model (MK-TRGM-BLUP) was used to predict total seed lipid content in an independent panel of 210 oat lines. The MK-TRGM-BLUP approach significantly improved predictions for total lipid content when compared to a conventional genomic BLUP (gBLUP) approach. Given that the MK-TGRM-BLUP approach leverages information on the nine fatty acids to predict genetic values for total lipid content in unobserved individuals, we compared the MK-TGRM-BLUP approach to a multi-trait gBLUP (MT-gBLUP) approach that jointly fits phenotypes for fatty acids and total lipid content. The MK-TGRM-BLUP approach significantly outperformed MT-gBLUP. Collectively, these results highlight the utility of using TGRM to accommodate information on endophenotypes and improve genomic prediction for a conventional agronomic trait. [ABSTRACT FROM AUTHOR]

Anterior cruciate ligament (ACL) rupture is a common condition that disproportionately affects young people, 50% of whom will develop knee osteoarthritis (OA) within 10 years of rupture. ACL rupture exhibits both hereditary and environmental risk factors, but the genetic basis of the disease remains unexplained. Spontaneous ACL rupture in the dog has a similar disease presentation and progression, making it a valuable genomic model for ACL rupture. We leveraged the dog model with Bayesian mixture model (BMM) analysis (BayesRC) to identify novel and relevant genetic variants associated with ACL rupture. We performed RNA sequencing of ACL and synovial tissue and assigned single nucleotide polymorphisms (SNPs) within differentially expressed genes to biological prior classes. SNPs with the largest effects were on chromosomes 3, 5, 7, 9, and 24. Selection signature analysis identified several regions under selection in ACL rupture cases compared to controls. These selection signatures overlapped with genome-wide associations with ACL rupture as well as morphological traits. Notable findings include differentially expressed ACSF3 with MC1R (coat color) and an association on chromosome 7 that overlaps the boundaries of SMAD2 (weight and body size). Smaller effect associations were within or near genes associated with regulation of the actin cytoskeleton and the extracellular matrix, including several collagen genes. The results of the current analysis are consistent with previous work published by our laboratory and others, and also highlight new genes in biological pathways that have not previously been associated with ACL rupture. The genetic associations identified in this study mirror those found in human beings, which lays the groundwork for development of disease-modifying therapies for both species. [ABSTRACT FROM AUTHOR]

Meeting the needs of a growing world population in the face of imminent climate change is a challenge; breeding of vegetable and oilseed Brassica crops is part of the race in meeting these demands. Available genetic diversity constituting the foundation of breeding is essential in plant improvement. Elite varieties, land races, and crop wild species are important resources of useful variation and are available from existing genepools or genebanks. Conservation of diversity in genepools, genebanks, and even the wild is crucial in preventing the loss of variation for future breeding efforts. In addition, the identification of suitable parental lines and alleles is critical in ensuring the development of resilient Brassica crops. During the past two decades, an increasing number of high-quality nuclear and organellar Brassica genomes have been assembled. Whole-genome re-sequencing and the development of pan-genomes are overcoming the limitations of the single reference genome and provide the basis for further exploration. Genomic and complementary omic tools such as microarrays, transcriptomics, epigenetics, and reverse genetics facilitate the study of crop evolution, breeding histories, and the discovery of loci associated with highly sought-after agronomic traits. Furthermore, in genomic selection, predicted breeding values based on phenotype and genome-wide marker scores allow the preselection of promising genotypes, enhancing genetic gains and substantially quickening the breeding cycle. It is clear that genomics, armed with diversity, is set to lead the way in Brassica improvement; however, a multidisciplinary plant breeding approach that includes phenotype = genotype × environment × management interaction will ultimately ensure the selection of resilient Brassica varieties ready for climate change. [ABSTRACT FROM AUTHOR]

The north-western Indian Himalayas possesses vast diversity in common bean germplasm due to several years of natural adaptation and farmer's selection. Systematic efforts have been made for the first time for the characterization and use of this huge diversity for the identification of genes/quantitative trait loci (QTLs) for yield and yield-contributing traits in common bean in India. A core set of 96 diverse common bean genotypes was characterized using 91 genome-wide genomic and genic simple sequence repeat (SSR) markers. The study of genetic diversity led to the identification of 691 alleles ranging from 2 to 21 with an average of 7.59 alleles/locus. The gene diversity (expected heterozygosity, He) varied from 0.31 to 0.93 with an average of 0.73. As expected, the genic SSR markers detected less allelic diversity than the random genomic SSR markers. The traditional clustering and Bayesian clustering (structural analysis) analyses led to a clear cut separation of a core set of 96 genotypes into two distinct groups based on their gene pools (Mesoamerican and Andean genotypes). Genome-wide association mapping for pods/plant, seeds/pod, seed weight, and yield/plant led to the identification of 39 significant marker–trait associations (MTAs) including 15 major, 15 stable, and 13 both major and stable MTAs. Out of 39 MTAs detected, 29 were new MTAs reported for the first time, whereas the remaining 10 MTAs were already identified in earlier studies and therefore declared as validation of earlier results. A set of seven markers was such, which were found to be associated with multiple (two to four) different traits. The important MTAs will be used for common bean molecular breeding programs worldwide for enhancing common bean yield. [ABSTRACT FROM AUTHOR]

Prediction of growth-related complex traits is highly important for crop breeding. Photosynthesis efficiency and biomass are direct indicators of overall plant performance and therefore even minor improvements in these traits can result in significant breeding gains. Crop breeding for complex traits has been revolutionized by technological developments in genomics and phenomics. Capitalizing on the growing availability of genomics data, genome-wide marker-based prediction models allow for efficient selection of the best parents for the next generation without the need for phenotypic information. Until now such models mostly predict the phenotype directly from the genotype and fail to make use of relevant biological knowledge. It is an open question to what extent the use of such biological knowledge is beneficial for improving genomic prediction accuracy and reliability. In this study, we explored the use of publicly available biological information for genomic prediction of photosynthetic light use efficiency (Φ PSII ) and projected leaf area (PLA) in Arabidopsis thaliana. To explore the use of various types of knowledge, we mapped genomic polymorphisms to Gene Ontology (GO) terms and transcriptomics-based gene clusters, and applied these in a Genomic Feature Best Linear Unbiased Predictor (GFBLUP) model, which is an extension to the traditional Genomic BLUP (GBLUP) benchmark. Our results suggest that incorporation of prior biological knowledge can improve genomic prediction accuracy for both Φ PSII and PLA. The improvement achieved depends on the trait, type of knowledge and trait heritability. Moreover, transcriptomics offers complementary evidence to the Gene Ontology for improvement when used to define functional groups of genes. In conclusion, prior knowledge about trait-specific groups of genes can be directly translated into improved genomic prediction. [ABSTRACT FROM AUTHOR]

Durum wheat is an important crop for the human diet and its consumption is gaining popularity. In order to ensure that durum wheat production maintains the pace with the increase in demand, it is necessary to raise productivity by approximately 1.5% per year. To deliver this level of annual genetic gain the incorporation of molecular strategies has been proposed as a key solution. Here, four RILs populations were used to conduct QTL discovery for grain yield (GY) and 1,000 kernel weight (TKW). A total of 576 individuals were sown at three locations in Morocco and one in Lebanon. These individuals were genotyped by sequencing with 3,202 high-confidence polymorphic markers, to derive a consensus genetic map of 2,705.7 cM, which was used to impute any missing data. Six QTLs were found to be associated with GY and independent from flowering time on chromosomes 2B, 4A, 5B, 7A and 7B, explaining a phenotypic variation (PV) ranging from 4.3 to 13.4%. The same populations were used to train genomic prediction models incorporating the relationship matrix, the genotype by environment interaction, and marker by environment interaction, to reveal significant advantages for models incorporating the marker effect. Using training populations (TP) in full sibs relationships with the validation population (VP) was shown to be the only effective strategy, with accuracies reaching 0.35–0.47 for GY. Reducing the number of markers to 10% of the whole set, and the TP size to 20% resulted in non-significant changes in accuracies. The QTLs identified were also incorporated in the models as fixed effects, showing significant accuracy gain for all four populations. Our results confirm that the prediction accuracy depends considerably on the relatedness between TP and VP, but not on the number of markers and size of TP used. Furthermore, feeding the model with information on markers associated with QTLs increased the overall accuracy.

This study assessed the accuracy and bias of genomic prediction (GP) in purebred Holstein (H) and Jersey (J) as well as crossbred (H and J) validation cows using different reference sets and prediction strategies. The reference sets were made up of different combinations of 36,695 H and J purebreds and crossbreds. Additionally, the effect of using different sets of marker genotypes on GP was studied (conventional panel: 50k, custom panel enriched with, or close to, causal mutations: XT_50k, and conventional high-density with a limited custom set: pruned HDnGBS). We also compared the use of genomic best linear unbiased prediction (GBLUP) and Bayesian (emBayesR) models, and the traits tested were milk, fat, and protein yields. On average, by including crossbred cows in the reference population, the prediction accuracies increased by 0.01–0.08 and were less biased (regression coefficient closer to 1 by 0.02–0.16), and the benefit was greater for crossbreds compared to purebreds. The accuracy of prediction increased by 0.02 using XT_50k compared to 50k genotypes without affecting the bias. Although using pruned HDnGBS instead of 50k also increased the prediction accuracy by about 0.02, it increased the bias for purebred predictions in emBayesR models. Generally, emBayesR outperformed GBLUP for prediction accuracy when using 50k or pruned HDnGBS genotypes, but the benefits diminished with XT_50k genotypes. Crossbred predictions derived from a joint pure H and J reference were similar in accuracy to crossbred predictions derived from the two separate purebred reference sets and combined proportional to breed composition. However, the latter approach was less biased by 0.13. Most interestingly, using an equalized breed reference instead of an H-dominated reference, on average, reduced the bias of prediction by 0.16–0.19 and increased the accuracy by 0.04 for crossbred and J cows, with a little change in the H accuracy. In conclusion, we observed improved genomic predictions for both crossbreds and purebreds by equalizing breed contributions in a mixed breed reference that included crossbred cows. Furthermore, we demonstrate, that compared to the conventional 50k or high-density panels, our customized set of 50k sequence markers improved or matched the prediction accuracy and reduced bias with both GBLUP and Bayesian models. [ABSTRACT FROM AUTHOR]

The last several years have witnessed an explosion of methods and applications for combining image data with 'omics data, and for prediction of clinical phenotypes. Much of this research has focused on cancer histology, for which genetic perturbations are large, and the signal to noise ratio is high. Related research on chronic, complex diseases is limited by tissue sample availability, lower genomic signal strength, and the less extreme and tissue-specific nature of intermediate histological phenotypes. Data from the GTEx Consortium provides a unique opportunity to investigate the connections among phenotypic histological variation, imaging data, and 'omics profiling, from multiple tissue-specific phenotypes at the sub-clinical level. Investigating histological designations in multiple tissues, we survey the evidence for genomic association and prediction of histology, and use the results to test the limits of prediction accuracy using machine learning methods applied to the imaging data, genomics data, and their combination. We find that expression data has similar or superior accuracy for pathology prediction as our use of imaging data, despite the fact that pathological determination is made from the images themselves. A variety of machine learning methods have similar performance, while network embedding methods offer at best limited improvements. These observations hold across a range of tissues and predictor types. The results are supportive of the use of genomic measurements for prediction, and in using the same target tissue in which pathological phenotyping has been performed. Although this last finding is sensible, to our knowledge our study is the first to demonstrate this fact empirically. Even while prediction accuracy remains a challenge, the results show clear evidence of pathway and tissue-specific biology. [ABSTRACT FROM AUTHOR]

Livestock breeding has shifted during the past decade toward genomic selection. For the estimation of breeding values in purebred breeding schemes, genomic best linear unbiased prediction has become the method of choice. Systematic crossbreeding with the aim to utilize heterosis and breed complementary effects is widely used in livestock breeding, especially in pig and poultry breeding. The goal is to improve the performance of the crossbred animals. Due to genotype-by-environment interactions, imperfect linkage disequilibrium, and the existence of dominance and imprinting, purebred and crossbred performances are not perfectly correlated. Hence, more complex genomic models are required for crossbred populations. This study reviews and compares such models. Compared to purebred genomic models, the reviewed models were of much higher complexity due to the inclusion of dominance effects, breed-specific effects, imprinting effects, and the joint evaluation of purebred and crossbred performance data. With the model assessment work conducted until now, it is not possible to come to a clear recommendation as to which existing method is most suitable for a specific breeding program and a specific genetic trait architecture. Since it is expected that a superior method includes all the different genetic effects in a single model, a dominance model with imprinting and breed-specific SNP effects is proposed. Further progress could be made by assuming realistic covariance structures between the genetic effects of the different breeding lines, and by using larger marker panels and mixture distributions for the SNP effects. [ABSTRACT FROM AUTHOR]

Various methods have been proposed for genomic prediction (GP) in livestock. These methods have mainly focused on statistical considerations and did not include genome annotation information. In this study, to improve the predictive performance of carcass traits in Chinese Simmental beef cattle, we incorporated the genome annotation information into GP. Single nucleotide polymorphisms (SNPs) were annotated to five genomic classes: intergenic, gene, exon, protein coding sequences, and 3′/5′ untranslated region. Haploblocks were constructed for all markers and these five genomic classes by defining a biologically functional unit, and haplotype effects were modeled in both numerical dosage and categorical coding strategies. The first-order epistatic effects among SNPs and haplotypes were modeled using a categorical epistasis model. For all makers, the extension from the SNP-based model to a haplotype-based model improved the accuracy by 5.4–9.8% for carcass weight (CW), live weight (LW), and striploin (SI). For the five genomic classes using the haplotype-based prediction model, the incorporation of gene class information into the model improved the accuracies by an average of 1.4, 2.1, and 1.3% for CW, LW, and SI, respectively, compared with their corresponding results for all markers. Including the first-order epistatic effects into the prediction models improved the accuracies in some traits and genomic classes. Therefore, for traits with moderate-to-high heritability, incorporating genome annotation information of gene class into haplotype-based prediction models could be considered as a promising tool for GP in Chinese Simmental beef cattle, and modeling epistasis in prediction can further increase the accuracy to some degree. [ABSTRACT FROM AUTHOR]

Linkage disequilibrium (LD), often expressed in terms of the squared correlation (r 2) between allelic values at two loci, is an important concept in many branches of genetics and genomics. Genetic drift and recombination have opposite effects on LD, and thus r 2 will keep changing until the effects of these two forces are counterbalanced. Several approximations have been used to determine the expected value of r 2 at equilibrium in the presence or absence of mutation. In this paper, we propose a probability-based approach to compute the exact distribution of allele frequencies at two loci in a finite population at any generation t conditional on the distribution at generation t − 1. As r 2 is a function of this distribution of allele frequencies, this approach can be used to examine the distribution of r 2 over generations as it approaches equilibrium. The exact distribution of LD from our method is used to describe, quantify, and compare LD at different equilibria, including equilibrium in the absence or presence of mutation, selection, and filtering by minor allele frequency. We also propose a deterministic formula for expected LD in the presence of mutation at equilibrium based on the exact distribution of LD. [ABSTRACT FROM AUTHOR]

Genomic selection increases the rate of genetic gain in breeding programs, which results in significant cumulative improvements in commercially important traits such as disease resistance. Genomic selection currently relies on collecting genome-wide genotype data accross a large number of individuals, which requires substantial economic investment. However, global aquaculture production predominantly occurs in small and medium sized enterprises for whom this technology can be prohibitively expensive. For genomic selection to benefit these aquaculture sectors, more cost-efficient genotyping is necessary. In this study the utility of low and medium density SNP panels (ranging from 100 to 9,000 SNPs) to accurately predict breeding values was tested and compared in four aquaculture datasets with different characteristics (species, genome size, genotyping platform, family number and size, total population size, and target trait). The traits show heritabilities between 0.19–0.49, and genomic prediction accuracies using the full density panel of 0.55–0.87. A consistent pattern of genomic prediction accuracy was observed across species with little or no accuracy reduction until SNP density was reduced below 1,000 SNPs (prediction accuracies of 0.44–0.75). Below this SNP density, heritability estimates and genomic prediction accuracies tended to be lower and more variable (93% of maximum accuracy achieved with 1,000 SNPs, 89% with 500 SNPs, and 70% with 100 SNPs). A notable drop in accuracy was observed between 200 SNP panels (0.44–0.75) and 100 SNP panels (0.39–0.66). Now that a multitude of studies have highlighted the benefits of genomic over pedigree-based prediction of breeding values in aquaculture species, the results of the current study highlight that these benefits can be achieved at lower SNP densities and at lower cost, raising the possibility of a broader application of genetic improvement in smaller and more fragmented aquaculture settings. [ABSTRACT FROM AUTHOR]

Linear type traits describing the skeletal characteristics of an animal are moderately to strongly genetically correlated with a range of other performance traits in cattle including feed intake, reproduction traits and carcass merit; thus, type traits could also provide useful insights into the morphological differences among animals underpinning phenotypic differences in these complex traits. The objective of the present study was to identify genomic regions associated with five subjectively scored skeletal linear traits, to determine if these associated regions are common in multiple beef and dairy breeds, and also to determine if these regions overlap with those proposed elsewhere to be associated with correlated performance traits. Analyses were carried out using linear mixed models on imputed whole genome sequence data separately in 1,444 Angus, 1,129 Hereford, 6,433 Charolais, 8,745 Limousin, 1,698 Simmental, and 4,494 Holstein-Friesian cattle, all scored for the linear type traits. There was, on average, 18 months difference in age at assessment of the beef versus the dairy animals. While the majority of the identified quantitative trait loci (QTL), and thus genes, were both trait-specific and breed-specific, a large-effect pleiotropic QTL on BTA6 containing the NCAPG and LCORL genes was associated with all skeletal traits in the Limousin population and with wither height in the Angus. Other than that, little overlap existed in detected QTLs for the skeletal type traits in the other breeds. Only two QTLs overlapped the beef and dairy breeds; both QTLs were located on BTA5 and were associated with height in both the Angus and the Holstein-Friesian, despite the difference in age at assessment. Several detected QTLs in the present study overlapped with QTLs documented elsewhere that are associated with carcass traits, feed intake, and calving difficulty. While most breeding programs select for the macro-traits like carcass weight, carcass conformation, and feed intake, the higher degree of granularity with selection on the individual linear type traits in a multi-trait index underpinning the macro-level goal traits, presents an opportunity to help resolve genetic antagonisms among morphological traits in the pursuit of the animal with optimum performance metrics. [ABSTRACT FROM AUTHOR]

Studying the impact of genetic variation on gene regulatory networks is essential to understand the biological mechanisms by which genetic variation causes variation in phenotypes. Bayesian networks provide an elegant statistical approach for multi-trait genetic mapping and modelling causal trait relationships. However, inferring Bayesian gene networks from high-dimensional genetics and genomics data is challenging, because the number of possible networks scales super-exponentially with the number of nodes, and the computational cost of conventional Bayesian network inference methods quickly becomes prohibitive. We propose an alternative method to infer high-quality Bayesian gene networks that easily scales to thousands of genes. Our method first reconstructs a node ordering by conducting pairwise causal inference tests between genes, which then allows to infer a Bayesian network via a series of independent variable selection problems, one for each gene. We demonstrate using simulated and real systems genetics data that this results in a Bayesian network with equal, and sometimes better, likelihood than the conventional methods, while having a significantly higher overlap with groundtruth networks and being orders of magnitude faster. Moreover our method allows for a unified false discovery rate control across genes and individual edges, and thus a rigorous and easily interpretable way for tuning the sparsity level of the inferred network. Bayesian network inference using pairwise node ordering is a highly efficient approach for reconstructing gene regulatory networks when prior information for the inclusion of edges exists or can be inferred from the available data. [ABSTRACT FROM AUTHOR]

Population management has the primary task of maximizing the long-term competitiveness of a breed. Breeds compete with each other for being able to supply consumer demands at low costs and also for funds from conservation programs. The competition for consumer preference is won by breeds with high genetic gain for total merit who maintained a sufficiently high genetic diversity, whereas the competition for funds is won by breeds with high conservation value. The conservation value of a breed could be improved by increasing its contribution to the gene pool of the species. This may include the recovery of its original genetic background and the maintenance of a high genetic diversity at native haplotype segments. The primary objective of a breeding program depends on the genetic state of the population and its intended usage. In this paper, we review the key genetic parameters that are relevant for population management, compare the methods for estimating them, derive the formulas for predicting their value at a future time, and clarify their usage in various types of breeding programs that differ in their main objectives. These key parameters are kinships, native kinships, breeding values, Mendelian sampling variances, native contributions, and mutational effects. Population management currently experiences a transition from using pedigree-based estimates to marker-based estimates, which improves the accuracies of these estimates and thereby increases response to selection. In addition, improved measures of the factors that determine the competitiveness of a breed and utilize auxiliary parameters, such as Mendelian sampling variances, mutational effects, and native kinships, enable to improve further upon historic recommendations for genetic population management. [ABSTRACT FROM AUTHOR]

The African continent is home to diverse populations of livestock breeds adapted to harsh environmental conditions with more than 70% under traditional systems of management. Animal productivity is less than optimal in most cases and is faced with numerous challenges including limited access to adequate nutrition and disease management, poor institutional capacities and lack of adequate government policies and funding to develop the livestock sector. Africa is home to about 1.3 billion people and with increasing demand for animal proteins by an ever growing human population, the current state of livestock productivity creates a significant yield gap for animal products. Although a greater section of the population, especially those living in rural areas depend largely on livestock for their livelihoods; the potential of the sector remains underutilized and therefore unable to contribute significantly to economic development and social wellbeing of the people. With current advances in livestock management practices, breeding technologies and health management, and with inclusion of all stakeholders, African livestock populations can be sustainably developed to close the animal protein gap that exists in the continent. In particular, advances in gene technologies, and application of genomic breeding in many Western countries has resulted in tremendous gains in traits like milk production with the potential that, implementation of genomic selection and other improved practices (nutrition, healthcare, etc.) can lead to rapid improvement in traits of economic importance in African livestock populations. The African livestock populations in the context of this review are limited to cattle, goat, pig, poultry, and sheep, which are mainly exploited for meat, milk, and eggs. This review examines the current state of livestock productivity in Africa, the main challenges faced by the sector, the role of various stakeholders and discusses in-depth strategies that can enable the application of genomic technologies for rapid improvement of livestock traits of economic importance. [ABSTRACT FROM AUTHOR]

Salmonella enterica serovar Gallinarum causes devastating outbreaks of fowl typhoid across the globe, especially in developing countries. With the use of antimicrobial agents being reduced due to legislation and the absence of licensed vaccines in some parts of the world, an attractive complementary control strategy is to breed chickens for increased resistance to Salmonella. The potential for genetic control of salmonellosis has been demonstrated by experimental challenge of inbred populations. Quantitative trait loci (QTL) associated with resistance have been identified in many genomic regions. A major QTL associated with systemic salmonellosis has been identified in a region termed SAL1. In the present study, two outbreaks of fowl typhoid in 2007 and 2012 in the United Kingdom were used to investigate the genetic architecture of Salmonella resistance in commercial laying hens. In the first outbreak 100 resistant and 150 susceptible layers were genotyped using 11 single nucleotide polymorphism (SNP) and 3 microsatellite markers located in the previously identified SAL1 region on chromosome 5. From the second outbreak 100 resistant and 200 susceptible layers, belonging to a different line, were genotyped with a high-density (600 K) genome-wide SNP array. Substantial heritability estimates were obtained in both populations (h 2 = 0.22 and 0.26, for the layers in the first and second outbreak, respectively). Significant associations with three markers on chromosome 5 located close to AKT1 and SIVA1 genes, coding for RAC-alpha serine/threonine protein kinase, and the CD27-binding protein SIVA1 , respectively, were identified in the first outbreak. From analysis of the second outbreak, eight genome-wide significant associations with Salmonella resistance were identified on chromosomes 1, 6, 7, 11, 23, 24, 26, 28 and several others with suggestive genome-wide significance were found. Pathway and network analysis revealed the presence of many innate immune pathways related to Salmonella resistance. Although, significant associations with SNPs located in the SAL1 locus were not identified by the genome-wide scan for layers from the second outbreak, pathway analysis revealed P13K/AKT signaling as the most significant pathway. In summary, resistance to fowl typhoid is a heritable polygenic trait that could possibly be enhanced through selective breeding. [ABSTRACT FROM AUTHOR]

Behavioral and cognitive traits have a genetic component even though contributions from individual genes and genomic loci are in many cases modest. Changes in the environment can alter genotype–phenotype relationships. Space travel, which includes exposure to ionizing radiation, constitutes environmental challenges and is expected to induce not only dramatic behavioral and cognitive changes but also has the potential to induce physical DNA damage. In this study, we utilized a genetically heterogeneous mouse model, dense genotype data, and shifting environmental challenges, including ionizing radiation exposure, to explore and quantify the size and stability of the genetic component of fear learning and memory-related measures. Exposure to ionizing radiation and other external stressors altered the genotype–phenotype correlations, although different behavioral and cognitive measures were affected to different extents. Utilizing an integrative genomic approach, we identified pathways and functional ontology categories associated with these behavioral and cognitive measures. [ABSTRACT FROM AUTHOR]

In the last years, a series of methods for genomic prediction (GP) have been established, and the advantages of GP over pedigree best linear unbiased prediction (BLUP) have been reported. However, the majority of previously proposed GP models are purely based on mathematical considerations while seldom take the abundant biological knowledge into account. Prediction ability of those models largely depends on the consistency between the statistical assumptions and the underlying genetic architectures of traits of interest. In this study, gene annotation information was incorporated into GP models by constructing haplotypes with SNPs mapped to genic regions. Haplotype allele similarity between pairs of individuals was measured through different approaches at single gene level and then converted into whole genome level, which was then treated as a special kernel and used in kernel based GP models. Results shown that the gene annotation guided methods gave higher or at least comparable predictive ability in some traits, especially in the Arabidopsis dataset and the rice breeding population. Compared to SNP models and haplotype models without gene annotation, the gene annotation based models improved the predictive ability by 0.56~26.67% in the Arabidopsis and 1.62~16.53% in the rice breeding population, respectively. However, incorporating gene annotation slightly improved the predictive ability for several traits but did not show any extra gain for the rest traits in a chicken population. In conclusion, integrating gene annotation into GP models could be beneficial for some traits, species, and populations compared to SNP models and haplotype models without gene annotation. However, more studies are yet to be conducted to implicitly investigate the characteristics of these gene annotation guided models. [ABSTRACT FROM AUTHOR]

The high genetic complexity found in heterogeneous stock (HS-CC) mice, together with selective breeding, can be used to detect new pathways and mechanisms associated with ethanol preference and excessive ethanol consumption. We predicted that these pathways would provide new targets for therapeutic manipulation. Previously (Colville et al., 2017), we observed that preference selection strongly affected the accumbens shell (SH) genes associated with synaptic function and in particular genes associated with synaptic tethering. Here we expand our analyses to include substantially larger sample sizes and samples from two additional components of the “addiction circuit,” the central nucleus of the amygdala (CeA) and the prelimbic cortex (PL). At the level of differential expression (DE), the majority of affected genes are region-specific; only in the CeA did the DE genes show a significant enrichment in GO annotation categories, e.g., neuron part. In all three brain regions the differentially variable genes were significantly enriched in a single network module characterized by genes associated with cell-to-cell signaling. The data point to glutamate plasticity as being a key feature of selection for ethanol preference. In this context the expression of Dlg2 which encodes for PSD-93 appears to have a key role. It was also observed that the expression of the clustered protocadherins was strongly associated with preference selection. [ABSTRACT FROM AUTHOR]

Sea lice are parasitic copepods that cause large economic losses to salmon aquaculture worldwide. Frequent chemotherapeutic treatments are typically required to control this parasite, and alternative measures such as breeding for improved host resistance are desirable. Insight into the host-parasite interaction and mechanisms of host resistance can lead to improvements in selective breeding, and potentially novel treatment targets. In this study, RNA sequencing was used to study the skin transcriptome of Atlantic salmon (Salmo salar) parasitized with sea lice (Caligus rogercresseyi). The overall aims were to compare the transcriptomic profile of skin at louse attachment sites and "healthy" skin, and to assess differences in gene expression response between animals with varying levels of resistance to the parasite. Atlantic salmon pre-smolts were challenged with C. rogercresseyi, growth and lice count measurements were taken for each fish. 21 animals were selected and RNA-Seq was performed on skin from a louse attachment site, and skin distal to attachment sites for each animal. These animals were classified into family-balanced groups according to the traits of resistance (high vs. low lice count), and growth during infestation. Overall comparison of skin from louse attachment sites vs. healthy skin showed that 4,355 genes were differentially expressed, indicating local up-regulation of several immune pathways and activation of tissue repair mechanisms. Comparison between resistant and susceptible animals highlighted expression differences in several immune response and pattern recognition genes, and also myogenic and iron availability factors. Components of the pathways involved in differential response to sea lice may be targets for studies aimed at improved or novel treatment strategies, or to prioritize candidate functional polymorphisms to enhance genomic selection for host resistance in commercial salmon breeding programs. [ABSTRACT FROM AUTHOR]

The analysis of large genomic data is hampered by issues such as a small number of observations and a large number of predictive variables (commonly known as “large P small N”), high dimensionality or highly correlated data structures. Machine learning methods are renowned for dealing with these problems. To date machine learning methods have been applied in Genome-Wide Association Studies for identification of candidate genes, epistasis detection, gene network pathway analyses and genomic prediction of phenotypic values. However, the utility of two machine learning methods, Gradient Boosting Machine (GBM) and Extreme Gradient Boosting Method (XgBoost), in identifying a subset of SNP makers for genomic prediction of breeding values has never been explored before. In this study, using 38,082 SNP markers and body weight phenotypes from 2,093 Brahman cattle (1,097 bulls as a discovery population and 996 cows as a validation population), we examined the efficiency of three machine learning methods, namely Random Forests (RF), GBM and XgBoost, in (a) the identification of top 400, 1,000, and 3,000 ranked SNPs; (b) using the subsets of SNPs to construct genomic relationship matrices (GRMs) for the estimation of genomic breeding values (GEBVs). For comparison purposes, we also calculated the GEBVs from (1) 400, 1,000, and 3,000 SNPs that were randomly selected and evenly spaced across the genome, and (2) from all the SNPs. We found that RF and especially GBM are efficient methods in identifying a subset of SNPs with direct links to candidate genes affecting the growth trait. In comparison to the estimate of prediction accuracy of GEBVs from using all SNPs (0.43), the 3,000 top SNPs identified by RF (0.42) and GBM (0.46) had similar values to those of the whole SNP panel. The performance of the subsets of SNPs from RF and GBM was substantially better than that of evenly spaced subsets across the genome (0.18–0.29). Of the three methods, RF and GBM consistently outperformed the XgBoost in genomic prediction accuracy. [ABSTRACT FROM AUTHOR]

Across species and tissues and especially in the mammalian brain, production of gene isoforms is widespread. While gene expression coordination has been previously described as a scale-free coexpression network, the properties of transcriptome-wide isoform production coordination have been less studied. Here we evaluate the system-level properties of cosplicing in mouse, macaque, and human brain gene expression data using a novel network inference procedure. Genes are represented as vectors/lists of exon counts and distance measures sensitive to exon inclusion rates quantifies differences across samples. For all gene pairs, distance matrices are correlated across samples, resulting in cosplicing or cotranscriptional network matrices. We show that networks including cosplicing information are scale-free and distinct from coexpression. In the networks capturing cosplicing we find a set of novel hubs with unique characteristics distinguishing them from coexpression hubs: heavy representation in neurobiological functional pathways, strong overlap with markers of neurons and neuroglia, long coding lengths, and high number of both exons and annotated transcripts. Further, the cosplicing hubs are enriched in genes associated with autism spectrum disorders. Cosplicing hub homologs across eukaryotes show dramatically increasing intronic lengths but stable coding region lengths. Shared transcription factor binding sites increase coexpression but not cosplicing; the reverse is true for splicing-factor binding sites. Genes with protein-protein interactions have strong coexpression and cosplicing. Additional factors affecting the networks include shared microRNA binding sites, spatial colocalization within the striatum, and sharing a chromosomal folding domain. Cosplicing network patterns remain relatively stable across species. [ABSTRACT FROM AUTHOR]

Hereford is a major beef breed in the USA, and a sub-population, known as Line 1 (L1), was established in 1934 using two paternal half-sib bulls and 50 unrelated females. L1 has since been maintained as a closed population and selected for growth to one year of age. Objectives were to characterize the molecular genetic architecture of L1 (n = 240) by comparing a cross-section of L1 with the general U.S. Hereford population (AHA, n = 311), estimating effects of imposed selection within L1 based on allele frequencies at 50K SNP loci, and examining loci-specific effects of heterozygosity on the selection criterion. Animals were genotyped using the Illumina BovineSNP50 Beadchip, and SNP were mapped to UMD3.0 assembly of the bovine genome sequence. Average LD, measured by square of Pearson correlation, of adjacent SNP was 0.36 and 0.16 in L1 and AHA, respectively. Difference in LD between L1 and AHA decreased as SNP spacing increased. Persistence of phase between L1 and AHA decreased from 0.45 to 0.14 as SNP spacing increased from 50 kb to 5,000 kb. Extended haplotype homozygosity was greater in L1 than in AHA for 95.6% of the SNP. Knowledge of selection applied to L1 facilitated a novel approach to QTL discovery. Minor allele frequency was (FDR < 0.01) affected by cumulative selection differential at 191 out of 25,901 SNP. With the FDR relaxed to 0.05, 13 regions on BTA2, 5, 6, 9, 11, 14, 15, 18, 23 and 26 are co-located with previously identified QTL for growth. After adjustment of postweaning gain phenotypes for fixed effects and direct additive genetic effects, regression of residuals on genome-wide heterozygosity was -235.3 ± 91.6 kg. However, no SNP-specific loci where heterozygotes were significantly superior to the average of homozygotes were revealed (FDR ≥ 0.17). In conclusion, genome-wide SNP genotypes clarified effects of selection and inbreeding within L1 and differences in genomic architecture between the population segment L1 and the AHA population.

Hereford is a major beef breed in the USA, and a sub-population, known as Line 1 (L1), was established in 1934 using two paternal half-sib bulls and 50 unrelated females. L1 has since been maintained as a closed population and selected for growth to 1 year of age. Objectives were to characterize the molecular genetic architecture of L1 (n = 240) by comparing a cross-section of L1 with the general US. Hereford population (AHA, n = 311), estimating effects of imposed selection within L1 based on allele frequencies at 50 K SNP loci, and examining loci-specific effects of heterozygosity on the selection criterion. Animals were genotyped using the Illumina BovineSNP50 Beadchip, and SNP were mapped to UMD3.0 assembly of the bovine genome sequence. Average linkage disequilibrium (LD), measured by square of Pearson correlation, of adjacent SNP was 0.36 and 0.16 in L1 and AHA, respectively. Difference in LD between L1 and AHA decreased as SNP spacing increased. Persistence of phase between L1 and AHA decreased from 0.45 to 0.14 as SNP spacing increased from 50 to 5,000 kb. Extended haplotype homozygosity was greater in L1 than in AHA for 95.6% of the SNP. Knowledge of selection applied to L1 facilitated a novel approach to QTL discovery. Minor allele frequency was (FDR < 0.01) affected by cumulative selection differential at 191 out of 25,901 SNP. With the FDR relaxed to 0.05, 13 regions on BTA2, 5, 6, 9, 11, 14, 15, 18, 23, and 26 are co-located with previously identified QTL for growth. After adjustment of postweaning gain phenotypes for fixed effects and direct additive genetic effects, regression of residuals on genome-wide heterozygosity was -235.3 ± 91.6 kg. However, no SNP-specific loci where heterozygotes were significantly superior to the average of homozygotes were revealed (FDR ≥ 0.17). In conclusion, genome-wide SNP genotypes clarified effects of selection and inbreeding within L1 and differences in genomic architecture between the population segment L1 and the AHA population.