Dr. Raluca Mateescu does research in the area of beef cattle, sheep and goat molecular genetics. Most biological traits of economic importance in domestic animals have a complex inheritance (are influenced by many genes and the environment) and the long-term research goal is to unravel the genetic basis for the phenotypic variability in this type of trait. Her research uses recent advances in the animal genomics field with the goal of improving animal production efficiency and enhancing animal products for improved human health.
Consumer satisfaction and willingness to purchase the product again in the future are largely determined by the quality of eating experience at consumption. To address consumers' demand for high-quality products, the beef industry needs to use all tools at its disposal to deliver a product with superior eating quality and implementation of an effective genetic improvement program is a critical step toward this aim. Palatability is not based only on one characteristic but is based on the relationship of three characteristics - tenderness, juiciness, and flavor – and how they work or do not work together to determine beef eating satisfaction. These traits are impractical to improve through traditional selection (difficult and expensive to measure) but are ideal candidates for genomic selection if genetic markers that account for a worthwhile proportion of the variation could be identified.
In this webinar, Dr. Mateescu will focus on the use of SVS program to perform genome-wide association studies for individual traits describing beef palatability, identify chromosomal regions associated with these traits, estimate genomic breeding values and predict the accuracy of GEBV for palatability traits in beef.
Effect of energy source and level and sex on growth, performance and carcass ...Faisal A. Alshamiry
In the past, increasing the slaughter weights of lambs was a goal of the American Sheep Industry (Harrison and Crouse, 1978).
Recently the American Sheep Industry has had the difficulty of balancing the heavy slaughter weights of lambs with a desirable amount of fat thickness (American Lamb Industry Roadmap, 2013).
The American lamb industry would also like to improve the productivity of American lamb by improving the efficiency of gain when compared with the cost of production.
Dr. Joe Cassady - Effects of preweaning factors on sow lifetime productivityJohn Blue
Effects of preweaning factors on sow lifetime productivity - Dr. Joe Cassady, from the 2012 Allen D. Leman Swine Conference, September 15-18, St. Paul, Minnesota, USA.
More presentations at http://www.swinecast.com/2012-leman-swine-conference-material
The application of several genomic models for the analysis of small holde...ILRI
Presented by R. Mrode, H. Aliloo, C. Ekine, J. Ojango, D., J.P. Gibson and M. Okeyo at the Interbull Annual Meeting, Cincinnati, Ohio, USA, 22-24 June 2019
Effect of energy source and level and sex on growth, performance and carcass ...Faisal A. Alshamiry
In the past, increasing the slaughter weights of lambs was a goal of the American Sheep Industry (Harrison and Crouse, 1978).
Recently the American Sheep Industry has had the difficulty of balancing the heavy slaughter weights of lambs with a desirable amount of fat thickness (American Lamb Industry Roadmap, 2013).
The American lamb industry would also like to improve the productivity of American lamb by improving the efficiency of gain when compared with the cost of production.
Dr. Joe Cassady - Effects of preweaning factors on sow lifetime productivityJohn Blue
Effects of preweaning factors on sow lifetime productivity - Dr. Joe Cassady, from the 2012 Allen D. Leman Swine Conference, September 15-18, St. Paul, Minnesota, USA.
More presentations at http://www.swinecast.com/2012-leman-swine-conference-material
The application of several genomic models for the analysis of small holde...ILRI
Presented by R. Mrode, H. Aliloo, C. Ekine, J. Ojango, D., J.P. Gibson and M. Okeyo at the Interbull Annual Meeting, Cincinnati, Ohio, USA, 22-24 June 2019
Dr. Rob Knox - Gilt Management/Puberty Induction and Sow Longevity/Productivity John Blue
Gilt Management/Puberty Induction and Sow Longevity/Productivity - Dr. Rob Knox, University of Illinois, from the 2012 Allen D. Leman Swine Conference, September 15-18, St. Paul, Minnesota, USA.
Jon De Jong - Evaluating Strategic Pellet Feeding Regimens On Finishing Pig P...John Blue
Evaluating Strategic Pellet Feeding Regimens On Finishing Pig Performance, Stomach Morphology, And Carcass Characteristics - Jon De Jong, from the 2015 Allen D. Leman Swine Conference, September 19-22, 2015, St. Paul, Minnesota, USA.
More presentations at http://www.swinecast.com/2015-leman-swine-conference-material
Monitoring, evaluation and learning and summary of baselines for the LIVES pr...ILRI
Presented by Berhanu Gebremedhin, Dirk Hoekstra and Aklilu Bogale at the LIVES Commodity Value Chain Development Inception Workshop, Addis Ababa, 21–24 January 2013
Dr. Jeff Vallet - The Importance Of Nutrition During Gilt DevelopmentJohn Blue
The Importance Of Nutrition During Gilt Development - Dr. Jeff Vallet, from the 2015 Allen D. Leman Swine Conference, September 19-22, 2015, St. Paul, Minnesota, USA.
More presentations at http://www.swinecast.com/2015-leman-swine-conference-material
Dr. Mark Knauer - Evaluating Body Condition & Reproductive PerformanceJohn Blue
Evaluating Body Condition & Reproductive Performance - Dr. Mark Knauer, North Carolina State University, from the 2014 Allen D. Leman Swine Conference, September 15-16, 2014, St. Paul, Minnesota, USA.
More presentations at http://www.swinecast.com/2014-leman-swine-conference-material
An Overview of Genomic Selection and FertilityDAIReXNET
In this webinar, released July 18, 2016, Dr. Hansen joined us to discuss genomic selection as it relates to fertility traits. Learn about single nucleotide polymorphisms (SNPs), the challenges in selecting for reproductive traits, and some of the current work in overcoming those challenges.
Jennifer Patterson - Improving Efficiencies of Replacement Gilt ManagementJohn Blue
Improving Efficiencies of Replacement Gilt Management - Jennifer Patterson, from the 2018 Allen D. Leman Swine Conference, September 15-18, 2018, St. Paul, Minnesota, USA.
More presentations at http://www.swinecast.com/2018-leman-swine-conference-material
Metabolizable protein requirements of Dorper crossbred ram lambsFaisal A. Alshamiry
Estimates of Net protein (NP) and Metabolizable protein (MP) requirements for the maintenance and growth of crossbred ram lambs assessed by the comparative slaughter technique.
Application of nuclear and genomic technologies for improving livestock produ...ILRI
Presented by Raphael Mrode at the IAEA International Symposium on Sustainable Animal Production and Health—Current Status and Way Forward, Vienna, 28 June-2 July 2021
Genetics and genomic approaches for sustainable dairy cattle improvement in s...ILRI
Presented by Raphael Mrode, Chinyere Ekine-Dzivenu, Julie Ojango and Mwai Okeyo at the ASAS-CSAS Annual Meeting & Trade Show, Oklahoma, USA, 26-30 June 2022
Genomic selection in small holder systems: Challenges and opportunitiesILRI
Presented by Raphael Mrode, Julie Ojango and Okeyo Mwai at the Workshop on Animal Genetic Research for Africa (Biosciences for Farming in Africa), Nairobi, 10-11 September 2015
Innovative digital technology and genomic approaches to dairy cattle genetic...ILRI
Presented by R. Mrode, J. Ojango, Ekine Chinyere, John Gibson and Okeyo Mwai at the Strategic Interest Research Group Meeting on Genetic Improvement of Livestock II, IITA, Ibadan, 2-3 September 2019
Predicting phenotypic traits from genotypes is a key focus in agrigenomics, as researchers and commercial farming operations work to increase crop yields and meat production to satisfy the needs of a growing global population. Genomic prediction allows these scientists to identify the plants or animals with the best breeding potential for desirable traits without having to go through lengthy and expensive field trials.
The Golden Helix SNP and Variation Suite (SVS) offers three methods for genomic prediction: Bayes C, Bayes C-pi and Genomic Best Linear Unbiased Predictors (GBLUP). This webcast will discuss the principles of genomic prediction. It describes how these methods are applied within SVS predicting phenotypes for both plant and animal species. In addition, we show how k-fold cross-validation can be utilized optimizing predictive models.
Population Structure & Genetic Improvement in LivestockGolden Helix Inc
The genetic improvement of livestock has been a hot topic for almost a century, bringing together researchers, industry, and producers to work towards a common goal. Many countries currently employ extensive genetic selection programs in their cattle with pigs, sheep, and chicken close behind.
In this webcast, Heather J. Huson, Ph.D. from Cornell University will focus on population dynamics and trait association in cattle and goats using high density SNP datasets. Population structure plays a critical role in understanding the relatedness among livestock, ancestral origins of traits, and identification of unique sub-populations or breeds for production improvement and conservation. This also lays the foundation for understanding and improving species such as the goat which is a vital food source in developing countries but has little recorded production or health data.
Understanding population structure is essential for designing complex trait association studies such as those related to production and health characteristics. Here, Huson shows examples of her lab's investigation into population structure in both goats and cattle to identify distinct groups and study traits such as thermo-tolerance.
Dr. Rob Knox - Gilt Management/Puberty Induction and Sow Longevity/Productivity John Blue
Gilt Management/Puberty Induction and Sow Longevity/Productivity - Dr. Rob Knox, University of Illinois, from the 2012 Allen D. Leman Swine Conference, September 15-18, St. Paul, Minnesota, USA.
Jon De Jong - Evaluating Strategic Pellet Feeding Regimens On Finishing Pig P...John Blue
Evaluating Strategic Pellet Feeding Regimens On Finishing Pig Performance, Stomach Morphology, And Carcass Characteristics - Jon De Jong, from the 2015 Allen D. Leman Swine Conference, September 19-22, 2015, St. Paul, Minnesota, USA.
More presentations at http://www.swinecast.com/2015-leman-swine-conference-material
Monitoring, evaluation and learning and summary of baselines for the LIVES pr...ILRI
Presented by Berhanu Gebremedhin, Dirk Hoekstra and Aklilu Bogale at the LIVES Commodity Value Chain Development Inception Workshop, Addis Ababa, 21–24 January 2013
Dr. Jeff Vallet - The Importance Of Nutrition During Gilt DevelopmentJohn Blue
The Importance Of Nutrition During Gilt Development - Dr. Jeff Vallet, from the 2015 Allen D. Leman Swine Conference, September 19-22, 2015, St. Paul, Minnesota, USA.
More presentations at http://www.swinecast.com/2015-leman-swine-conference-material
Dr. Mark Knauer - Evaluating Body Condition & Reproductive PerformanceJohn Blue
Evaluating Body Condition & Reproductive Performance - Dr. Mark Knauer, North Carolina State University, from the 2014 Allen D. Leman Swine Conference, September 15-16, 2014, St. Paul, Minnesota, USA.
More presentations at http://www.swinecast.com/2014-leman-swine-conference-material
An Overview of Genomic Selection and FertilityDAIReXNET
In this webinar, released July 18, 2016, Dr. Hansen joined us to discuss genomic selection as it relates to fertility traits. Learn about single nucleotide polymorphisms (SNPs), the challenges in selecting for reproductive traits, and some of the current work in overcoming those challenges.
Jennifer Patterson - Improving Efficiencies of Replacement Gilt ManagementJohn Blue
Improving Efficiencies of Replacement Gilt Management - Jennifer Patterson, from the 2018 Allen D. Leman Swine Conference, September 15-18, 2018, St. Paul, Minnesota, USA.
More presentations at http://www.swinecast.com/2018-leman-swine-conference-material
Metabolizable protein requirements of Dorper crossbred ram lambsFaisal A. Alshamiry
Estimates of Net protein (NP) and Metabolizable protein (MP) requirements for the maintenance and growth of crossbred ram lambs assessed by the comparative slaughter technique.
Application of nuclear and genomic technologies for improving livestock produ...ILRI
Presented by Raphael Mrode at the IAEA International Symposium on Sustainable Animal Production and Health—Current Status and Way Forward, Vienna, 28 June-2 July 2021
Genetics and genomic approaches for sustainable dairy cattle improvement in s...ILRI
Presented by Raphael Mrode, Chinyere Ekine-Dzivenu, Julie Ojango and Mwai Okeyo at the ASAS-CSAS Annual Meeting & Trade Show, Oklahoma, USA, 26-30 June 2022
Genomic selection in small holder systems: Challenges and opportunitiesILRI
Presented by Raphael Mrode, Julie Ojango and Okeyo Mwai at the Workshop on Animal Genetic Research for Africa (Biosciences for Farming in Africa), Nairobi, 10-11 September 2015
Innovative digital technology and genomic approaches to dairy cattle genetic...ILRI
Presented by R. Mrode, J. Ojango, Ekine Chinyere, John Gibson and Okeyo Mwai at the Strategic Interest Research Group Meeting on Genetic Improvement of Livestock II, IITA, Ibadan, 2-3 September 2019
Predicting phenotypic traits from genotypes is a key focus in agrigenomics, as researchers and commercial farming operations work to increase crop yields and meat production to satisfy the needs of a growing global population. Genomic prediction allows these scientists to identify the plants or animals with the best breeding potential for desirable traits without having to go through lengthy and expensive field trials.
The Golden Helix SNP and Variation Suite (SVS) offers three methods for genomic prediction: Bayes C, Bayes C-pi and Genomic Best Linear Unbiased Predictors (GBLUP). This webcast will discuss the principles of genomic prediction. It describes how these methods are applied within SVS predicting phenotypes for both plant and animal species. In addition, we show how k-fold cross-validation can be utilized optimizing predictive models.
Population Structure & Genetic Improvement in LivestockGolden Helix Inc
The genetic improvement of livestock has been a hot topic for almost a century, bringing together researchers, industry, and producers to work towards a common goal. Many countries currently employ extensive genetic selection programs in their cattle with pigs, sheep, and chicken close behind.
In this webcast, Heather J. Huson, Ph.D. from Cornell University will focus on population dynamics and trait association in cattle and goats using high density SNP datasets. Population structure plays a critical role in understanding the relatedness among livestock, ancestral origins of traits, and identification of unique sub-populations or breeds for production improvement and conservation. This also lays the foundation for understanding and improving species such as the goat which is a vital food source in developing countries but has little recorded production or health data.
Understanding population structure is essential for designing complex trait association studies such as those related to production and health characteristics. Here, Huson shows examples of her lab's investigation into population structure in both goats and cattle to identify distinct groups and study traits such as thermo-tolerance.
GWAS to Identify Genetics that Influence Calf Health from Holstein and Crossb...Delaina Hawkins
Genome-wide association analysis is a powerful tool for explaining the phenotypic effects of dairy cattle on the genome and knowledge of genes associated with dairy cattle phenotypes. SNP & Variation Suite (SVS) has assisted the University of Minnesota, West Central Research and Outreach Center to determine the association of genetics groups with calf and cow health. These results are used to improve selection indexes for genomic evaluations for dairy cattle and will help improve the profitability of dairy production systems.
The University of Minnesota, West Central Research and Outreach Center has 300-cow dairy and unique populations of dairy cattle. The herd is comprised of purebred Holsteins, 1964 genetic control purebred Holsteins and crossbreds of Holstein, Montbéliarde and Viking Red, and crossbreds of Jersey, Normande, and Viking Red. Their 1964 Holstein herd is essentially “frozen” in time from 1964, and is one of the last true genetics resources in the Holstein breed. This unique Holstein population remains unselected from 1964, and they maintain this unique Holstein population.
Their team has genotyped their Holstein cattle, and have genotyped over 250 Holstein calves and cows, and over 650 crossbred calves and cows. We have genotyped over 450 animals with the 40K Bovine chip and over 200 with the 150K Bovine HD chip. Currently, they are conducting additional analyses that include Runs of Homozygosity, signatures of selection, and haplotype blocks. Genome-wide association analysis identified a number of genes and chromosome regions associated with calf health in contemporary Holstein cows and 1964 Holstein cows.
Wrap Up Comments - Dr. Nevil Speer, NIAA Board Chair & Forum Moderator, from the NIAA 2018 Strategy Forum on Livestock Traceability, September 25 - 26, 2018, Kansas City, MO, USA.
More presentations at https://www.youtube.com/channel/UCeUDeS810OcOfuEYwj1oHKQ
Next-generation sequencing has enabled clinicians and researchers alike to identify novel genetic variants associated with rare Mendelian Diseases across the human genome. To help enable researchers and clinicians understand the role of CNVs in human health and disease, Golden Helix has integrated a specialized NGS-based CNV caller capable of detecting deletion and duplication events as small as single-exons and as large as whole chromosome aneuploidy events. In this webcast, we will present our workflows that integrates the NGS-based CNV caller into SVS.
This is the 5th and final presentation in a 5-part webinar series on Breeding Better Sheep & Goats. The presenter is Susan Schoenian, University of Maryland Extension Sheep & Goat Specialist.
Utilization of NGS data and genomic selection to rescue an endangered and her...Golden Helix
The Florida Cracker Sheep (FCS) is one of the oldest sheep breeds in the United States. This heritage breed from Florida, naturally adapted to humid and hot climate conditions, is one of the most parasite resistant breeds from the Southern US. However, approximately 1,000 individuals remain alive in the world. Therefore, more research and conservational efforts are required to support all the FCS producers from Florida and rescue FCS from extinction.
Advancements in NGS technologies and reduction in genotyping costs have allowed the utilization of these tools in animal genetics and genomics. We followed up a FCS population (n = 350) from a commercial farm to evaluate parasite resistance traits (FEC, FAMACHA score, hematocrit) using a longitudinal study and genotyped 300 sheep using the GGP Ovine 50k array. Analysis with Golden Helix SVS software identified 15 SNPs with additive and non-additive effects associated with parasite resistance in chromosome 1, 2, 3, 6, 8, 10, 11,12, 13 and 21. Also, a deletion CNV was associated with parasite resistance (FEC) in chromosome 21. Some of these DNA variants were located in STAT5B, NRIPI, TRPM3, WC1, GPC5, CELF2 and RAB3IL genes which control immune response mechanisms in sheep.
Validation of these results and implementation of genomic selection utilizing information from NGS, SNP genotyping and WGS can be easily performed by Golden Helix SVS software. This will allow the implementation of breeding and conservational programs in FCS farms and will improve the profitability of farms over the long term by incorporating the use of genetically parasite resistant sheep and promote local sheep meat production in Florida.
Genomic selection changing Breeding programe around the world, talk consist of concept of Breeding, breeding value, Genomic breeding value, Genotype imputation, male calf procurement on basis of GEBV under SAG PT Project and 1000 bull genome project.
This is the second presentation from a six part webinar series on the National Sheep Improvement Program (NSIP). The presenter is Dr. Ken Andries from Kentucky State University. The date of the presentation was May 8, 2014.
Complementarity of value chain analysis, consumption patterns and nutrition i...ILRI
Presented by Paula Dominguez-Salas, Barbara Häsler, Elaine Ferguson, Laura Cornelsen, Silvia Alonso, Eric M. Fèvre, Jonathan Rushton, Delia Grace and Pablo Alarcon at the 5th Leverhulme Centre for Integrative Research on Agriculture and Health (LCIRAH) Annual Research Conference, London, UK, 3-4 June 2015.
Using VarSeq to Improve Variant Analysis Research WorkflowsDelaina Hawkins
Many questions must be answered when analyzing DNA sequence variants: How do I determine which variants are potentially deleterious? Is the sequencing quality sufficient? How do I prioritize the results? Which annotation sources may help answer my research question?
In this webinar presentation, we will review workflow strategies for quality control and analysis of DNA sequence variants using the VarSeq software package from Golden Helix. VarSeq is a powerful platform for analysis of DNA sequence variants in clinical and translational research settings. VarSeq provides researchers with easy access to curated public databases of variant annotation information, and also enables users to incorporate their own local databases or downloaded information about variants and genomic regions.
The presentation will include interactive demonstrations using VarSeq to analyze variants found by exome sequencing of an extended family with a complex disease. We will review strategies for assessing variant quality, applying genomic annotations, incorporating custom annotation sources, and creating variant filters in VarSeq. We will also demonstrate the PhoRank gene ranking algorithm and its application for prioritizing variants.
FOXO3 Regulates Fetal Hemoglobin Levels in Sickle Cell AnemiaDelaina Hawkins
Although individuals with sickle cell anemia ostensibly have a monogenetic disease, they exhibit wide variability in the degree of clinical severity. One of the most powerful and reproducible predictors of disease severity is the level of endogenous fetal hemoglobin (HbF), composed of two gamma-globin and two α-globin chains. Expression of HbF is reduced in infancy and little is known about how this regulation is accomplished. A better understanding of gamma-globin regulation could aid in the discovery and design of a specific gamma-globin inducing agent.
Taking a genomics approach to this question, Dr. Vivien Sheehan and her team investigated the natural human variation and its correlation with HbF levels to identify novel genes important for gamma-globin regulation. In this webinar, she describes how they performed whole exome sequencing (WES) and used gene-based analysis to find correlations between rare variants and endogenous HbF levels. T1 testing found seven unique non-synonymous variations in a Forkhead box O transcription factor, FOXO3, to be significantly associated with lower HbF (p=5.6x10-4, β-value ln HbF -0.66). They verified the association between FOXO3 and endogenous HbF levels in an ex vivo model of erythroid differentiation from CD34+ cells isolated from peripheral blood called primary erythroid culture.
These results strongly suggest that FOXO3 is a positive regulator of gamma-globin. The gamma-globin specific effect of FOXO3 is critical; FOXO3 is an excellent therapeutic target for the treatment of sickle cell disease, as it selectively induces HbF, which does not sickle, without inducing HbS. Also, FOXO3 does not delay erythroid maturation, instead it actually promotes erythroid maturation. Taken together, the results indicate that FOXO3 is a positive regulator of gamma-globin expression and an excellent therapeutic target for fetal hemoglobin induction. Their findings support a new mechanism underlying fetal hemoglobin regulation and help identify potential new HbF inducing agents.
Genetic Basis of Pyridoxine-Responsive Neonatal Epilepsy in Consanguineous Fa...Delaina Hawkins
Hilal Al-Shekaili is a PhD student at the University of British Columbia who conducts research in rare, autosomal recessive disorders, specifically pyridoxine-responsive epileptic encephalopathies (PREE). PREE is often characterized by recurrent seizures in the prenatal, neonatal, or postnatal period, which are typically resistant to conventional anticonvulsant treatment but are well-controlled by the administration of pyridoxine (vitamin B6). Hilal and his colleagues at UBC are undertaking a research project to identify novel genetic causes in unexplained forms of pyridoxine-dependent epilepsy (PDE), a special type of PREE with an estimated incidence of 1:20,000 to 1:750,000. In most affected infants, PDE is caused by mutations in the antiquitin gene (ALDH7A1) and subsequent inactivation of α-aminoadipic semialdehyde dehydrogenase (antiquitin, ATQ).
Currently, ALDH7A1 is the only gene for which mutations are known to underlie PDE. However, locus heterogeneity has been reported in some families and other genes seem to be involved. Nearly 5% of children with a typical clinical picture of PDE harbor no detectable mutation of ALDH7A1. Identifying causative genes in such families will likely lead to improved treatment for these patients and help unravel much of the unknown about pyridoxine metabolism in the human body.
In this webinar, Hilal will cover how he and his team used whole-genome SNP genotyping, genome-wide runs of homozygosity (RoH) mapping using SVS, and whole-exome sequencing to characterize the genetic defect underlying PREE in a consanguineous Omani Arab family with two affected children who have a PDE-like clinical picture but negative ATQ biomarkers.
As labs move genetic tests into production using VarSeq, we have been looking for ways to support more of their total workflow within the same integrated expertise used to annotate, filter and interpret variants.
With our upcoming release of VarSeq, we are introducing a powerful and flexible platform to author clinical reports, specialized to the needs of individual labs and tests.
This webcast shows the new VarSeq Reports add-on feature, as well as other components of the total clinical test workflow including:
Using VarSeq to lock down the exact bioinformatics steps to prepare variants for interpretation
Compute coverage statistics over targeted panel regions, with sample level summaries and visualization with the built-in GenomeBrowse visualization
Customize our ACMG compliant clinical reports for lab and test specific parameters
Go through an interpretation process, previewing and updating a report in real-time
Produce rendered reports in HTML and PDF formats
Use VarSeq Reports to export structured interpretation of variants, genes and sample's test results into customized formats for third party and LIMS/EMR integration
We have been excited to work with clinical labs that are running VarSeq to develop this add-on, and hope you enjoy the showcase of it for the first time in public.
SETBP1 as a novel candidate gene for neurodevelopmental disorders of speech a...Delaina Hawkins
The genetic etiology of neurodevelopmental disorders has proven elusive due to the substantial phenotypic and etiological heterogeneity of their common forms. Developmental language disorders affect approximately 7% of children and are associated with negative outcomes in a multitude of domains, including social, emotional, behavioral, and academic functioning. Yet, with the exception of several reported monogenic cases, they are severely understudied with respect to their genetic bases, as the field is effectively only entering its 'GWAS era'.
One of the possible solutions is to reduce the supposed phenotypic and locus heterogeneity by studying special populations such as genetic isolates. Taking this approach, Dr. Sergey Kornilov and Dr. Elena Grigorenko's team at Yale University performed a genome-wide association and whole exome sequencing study of members of a unique geographic Russian-speaking isolate, characterized by an unusually high prevalence (i.e., around 30%) of neurodevelopmental disorders of speech and language.
On one hand, the GWAS results suggested that at least part of the multivariate language disorder phenotype in this population is associated (surviving corrections for multiple testing) with variation in the SETBP1 gene. On the other hand, the WES revealed multiple potentially damaging exonic variants in severely affected probands in other genes that play a role in neural development. GWAS and WES converged on a new candidate pathway that is potentially affected by common as well as rare variation in this population. Preliminary follow-up studies using neural endophenotypes corroborated these findings by implicating SETBP1 in the atypical development of language-related cortical networks and highlighting it as a novel candidate language disorder gene.
In this webcast, Dr. Kornilov will delve into his team's GWAS and whole exome sequencing studies surrounding the neurodevelopmental disorders of speech and language in the unique, Russian sample set.
Clinical labs need to be able to process samples down to a shortlist of variants and publish a professional report. Two common clinical applications for genetic tests include Cancer Gene Panels and Whole Exome Trios. Using VarSeq and VSReports, we will demonstrate how easy it is to go from a variant file created by a secondary analysis pipeline containing unfiltered variants to a report containing information for variants of interest. Along the way, we will discuss tips and tricks and answer frequently asked questions to help you get the most out of your data!
This webcast will present a thorough overview of VarSeq's support for clinics:
Cancer Gene Panel:
- Variant, Region and Sample Quality Assurance
- Filtering to variants in targeted cancer genes relevant to the tumor type
- Summarizing variants in a clinical report
Whole Exome Trio:
- Variant Quality Assurance
- Filtering to variants matching several inheritance patterns
- Summarizing variants in a clinical report
Using NGS to detect CNVs in familial hypercholesterolemiaDelaina Hawkins
Familial hypercholesterolemia (FH) is a heritable condition of severely elevated LDL cholesterol, characterized by premature atherosclerotic cardiovascular disease. FH affects an estimated 1 in 250 individuals worldwide, and is considered to be the most frequent monogenic disorder encountered in clinical practice. Although FH has multiple genetic etiologies, the large majority of defined cases result from autosomal codominant mutations in the LDL receptor gene (LDLR).
In providing a molecular diagnosis for FH, the current procedure often includes targeted next-generation sequencing (NGS) panels for the detection of small-scale DNA variants, followed by multiplex ligation-dependent probe amplification (MLPA) in LDLR for the detection of whole-exon copy number variants (CNVs). The latter is essential as ~10% of FH cases are attributed to CNVs in LDLR; accounting for them decreases false-negative findings. Here, we have determined the potential of replacing MLPA with bioinformatic analysis (VarSeq) applied to NGS data, which uses depth of coverage analysis as its principal method to identify whole-exon CNV events. In analysis of 388 FH patient samples, there was 100% concordance in LDLR CNV detection between these two methods: 38 reported CNVs identified by MLPA were also successfully detected by NGS + VarSeq, while 350 samples negative for CNVs by MLPA were also negative by NGS + VarSeq. This result suggests that MLPA is dispensable, significantly reducing costs, resources, and analysis time associated with the routine diagnostic screening for FH, while promoting more widespread assessment of this important class of mutations across diagnostic laboratories.
Updates to VSClinical ACMG Guidelines & a Tour of Cancer Annotation SourcesDelaina Hawkins
Earlier this year we launched our latest product VSClinical featuring workflow support for the ACMG guidelines with advanced automation capabilities and per-criteria recommendations. It has been amazing to watch the adoption of this product in labs doing both germline and in some cases cancer variant interpretation. Our latest VarSeq 2.1 release demonstrates our approach to iterative product improvements based on our committed relationship with our customers and includes numerous enhancements to VSClinical.
In this webcast, we cover the new and updated capabilities that can add value to your genetic testing workflows as well as review the VarSeq workflow support somatic variant interpretation in tumors by leveraging our cancer-specific annotations sources. In this webcast, we:
-Demonstrate the new “Consortium Classification” support in VSClinical to have an additional ClinVar-like annotation source added to the automated and interactive ACMG scoring process.
-See how previous interpretations are integrated into your VSClinical analysis, whether they are for the current variant or are just in the genomic neighborhood.
-Cover the additional “Lookup in PubMed” variant search feature for finding supporting studies that may provide functional or clinical evidence for a variant.
-See in action the new ACMG Auto Scoring based templates for trio analysis and gene panel tests.
-Review somatic variant filtering and prioritizing in VarSeq and the updates to relevant public annotation sources including CiVIC, ICGC and a new and available to license COSMIC v86!
Defecation
Normal defecation begins with movement in the left colon, moving stool toward the anus. When stool reaches the rectum, the distention causes relaxation of the internal sphincter and an awareness of the need to defecate. At the time of defecation, the external sphincter relaxes, and abdominal muscles contract, increasing intrarectal pressure and forcing the stool out
The Valsalva maneuver exerts pressure to expel faeces through a voluntary contraction of the abdominal muscles while maintaining forced expiration against a closed airway. Patients with cardiovascular disease, glaucoma, increased intracranial pressure, or a new surgical wound are at greater risk for cardiac dysrhythmias and elevated blood pressure with the Valsalva maneuver and need to avoid straining to pass the stool.
Normal defecation is painless, resulting in passage of soft, formed stool
CONSTIPATION
Constipation is a symptom, not a disease. Improper diet, reduced fluid intake, lack of exercise, and certain medications can cause constipation. For example, patients receiving opiates for pain after surgery often require a stool softener or laxative to prevent constipation. The signs of constipation include infrequent bowel movements (less than every 3 days), difficulty passing stools, excessive straining, inability to defecate at will, and hard feaces
IMPACTION
Fecal impaction results from unrelieved constipation. It is a collection of hardened feces wedged in the rectum that a person cannot expel. In cases of severe impaction the mass extends up into the sigmoid colon.
DIARRHEA
Diarrhea is an increase in the number of stools and the passage of liquid, unformed feces. It is associated with disorders affecting digestion, absorption, and secretion in the GI tract. Intestinal contents pass through the small and large intestine too quickly to allow for the usual absorption of fluid and nutrients. Irritation within the colon results in increased mucus secretion. As a result, feces become watery, and the patient is unable to control the urge to defecate. Normally an anal bag is safe and effective in long-term treatment of patients with fecal incontinence at home, in hospice, or in the hospital. Fecal incontinence is expensive and a potentially dangerous condition in terms of contamination and risk of skin ulceration
HEMORRHOIDS
Hemorrhoids are dilated, engorged veins in the lining of the rectum. They are either external or internal.
FLATULENCE
As gas accumulates in the lumen of the intestines, the bowel wall stretches and distends (flatulence). It is a common cause of abdominal fullness, pain, and cramping. Normally intestinal gas escapes through the mouth (belching) or the anus (passing of flatus)
FECAL INCONTINENCE
Fecal incontinence is the inability to control passage of feces and gas from the anus. Incontinence harms a patient’s body image
PREPARATION AND GIVING OF LAXATIVESACCORDING TO POTTER AND PERRY,
An enema is the instillation of a solution into the rectum and sig
ICH Guidelines for Pharmacovigilance.pdfNEHA GUPTA
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Antibiotic Stewardship by Anushri Srivastava.pptxAnushriSrivastav
Stewardship is the act of taking good care of something.
Antimicrobial stewardship is a coordinated program that promotes the appropriate use of antimicrobials (including antibiotics), improves patient outcomes, reduces microbial resistance, and decreases the spread of infections caused by multidrug-resistant organisms.
WHO launched the Global Antimicrobial Resistance and Use Surveillance System (GLASS) in 2015 to fill knowledge gaps and inform strategies at all levels.
ACCORDING TO apic.org,
Antimicrobial stewardship is a coordinated program that promotes the appropriate use of antimicrobials (including antibiotics), improves patient outcomes, reduces microbial resistance, and decreases the spread of infections caused by multidrug-resistant organisms.
ACCORDING TO pewtrusts.org,
Antibiotic stewardship refers to efforts in doctors’ offices, hospitals, long term care facilities, and other health care settings to ensure that antibiotics are used only when necessary and appropriate
According to WHO,
Antimicrobial stewardship is a systematic approach to educate and support health care professionals to follow evidence-based guidelines for prescribing and administering antimicrobials
In 1996, John McGowan and Dale Gerding first applied the term antimicrobial stewardship, where they suggested a causal association between antimicrobial agent use and resistance. They also focused on the urgency of large-scale controlled trials of antimicrobial-use regulation employing sophisticated epidemiologic methods, molecular typing, and precise resistance mechanism analysis.
Antimicrobial Stewardship(AMS) refers to the optimal selection, dosing, and duration of antimicrobial treatment resulting in the best clinical outcome with minimal side effects to the patients and minimal impact on subsequent resistance.
According to the 2019 report, in the US, more than 2.8 million antibiotic-resistant infections occur each year, and more than 35000 people die. In addition to this, it also mentioned that 223,900 cases of Clostridoides difficile occurred in 2017, of which 12800 people died. The report did not include viruses or parasites
VISION
Being proactive
Supporting optimal animal and human health
Exploring ways to reduce overall use of antimicrobials
Using the drugs that prevent and treat disease by killing microscopic organisms in a responsible way
GOAL
to prevent the generation and spread of antimicrobial resistance (AMR). Doing so will preserve the effectiveness of these drugs in animals and humans for years to come.
being to preserve human and animal health and the effectiveness of antimicrobial medications.
to implement a multidisciplinary approach in assembling a stewardship team to include an infectious disease physician, a clinical pharmacist with infectious diseases training, infection preventionist, and a close collaboration with the staff in the clinical microbiology laboratory
to prevent antimicrobial overuse, misuse and abuse.
to minimize the developme
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3. Research program focus
•Genetic control of complex traits
• Major advances in animal genomics
• Improve animal production efficiency & enhance
animal products for human heath
Healthfulness Project: development of
genetic tools to improve nutritional and
health value of beef.
Mapping QTL for breeding out of
season and milk production in sheep
Sustainable small ruminant production through
selection for resistance to internal parasites
Genomics of resilience in
sheep to climatic stressors
Genomic tools to improve meat quality
traits in Angus-Brahman cattle.
4. •Project Goal:
• Assess the natural variation in healthfulness traits
• Identify genetic mechanism controlling these traits
• Develop tools to select for:
More nutritious beef
Tasty beef
Improved production
“Healthfulness Project”
Genetic evaluation for nutrient composition of beef could
result in development of gEBV to aid selection for:
• favorable fatty-acid profile
• lower levels of cholesterol and saturated fat
• higher concentrations of minerals and vitamins
5. Beef Healthfulness Project
• 3 Angus herds (n = 2,285): Iowa, Oklahoma, California
• Harvest: October 2007 – May 2008
• Growth
• Birth, weaning, yearling, slaughter weights
• Carcass
• Hot carcass weight, dressing %, ribeye area, back fat thickness,
yield grade, quality grade, KPH
• Meat Quality
• WBSF, Sensory panels (Juiciness, Tenderness, Connective tissue
& Flavor: beef, painty/fishy, livery/metallic), TBARS
• Nutritional value and Healthfulness
• Fatty acids, main FA groups (SFA, MUFA, PUFA, n3, n6), AI –
Triacylglycerol, Phospholipid, Composite
• Cholesterol, sphingolipids, creatine, creatinine, carnitine,
carnosine, anserine
• Minerals: iron, sodium, magnesium, manganese, zinc,
phosphorus, potassium, calcium, copper
• Vitamins: E, B6
All animals
genotyped with the
Illumina Bovine 50K
SNP Bead Chip
5 generation
pedigree
(n = 5,907)
6. • The National Beef Quality Audit
• Seedstock Producers, Cow-Calf Producers, Stockers/
Backgrounders, Feedlot Operators, Packers, Purveyors,
Retailers, & Restauranteurs
• “Eating satisfaction” - only quality category for which
the packers, food service buyers, and retailers are willing to
pay a premium
•NBQA Strategy Workshop
• Discuss the implications of research for the U.S. beef industry,
provides the beef industry with a blueprint for the next five years
• Top 10 Quality Challenges:
1. Low overall uniformity & consistency of cattle, carcasses,
cuts
2. Inappropriate carcass size & weight
3. Inadequate tenderness of beef
4. Insufficient marbling
What do consumers want?
7. 1991 1995 2000 2005 2011
External Fat Overall
Uniformity
Overall
Uniformity
Traceability Food Safety
Seam Fat Overall
Palatability
Carcass Weights Overall
Uniformity
Eating Satisfaction
Overall
Palatability
Marbling Tenderness Instrument
grading
How and where
cattle were raised
Tenderness Tenderness Marbling Market Signals Weight and Size
Overall
Cutability
External and
Seam Fat
Reduced quality
due to implants
Segmentation Lean, Fat and Bone
Marbling Cut weights External Fat Carcass
Weights
Cattle Genetics
National Beef Quality Audit
Quality Challenges
Ranked according to priority, 1991 to 2011
8. Specific recommendations to reduce barriers
and improve beef profitability
•Increase funding to improve eating satisfaction
•Use genetics to optimize cutability and
palatability
•Fit Cattle with Customer Expectations
• Assist producers with use of selection and
management techniques to produce cattle that fit
customer expectations and other value-
determining attributes
National Beef Quality Audit – 2011
9. • Trait measured after slaughter, expensive to
measure routinely, low consistency
• Currently USDA grading system (marbling and
maturity) is used to predict palatability of beef
• Changes in consumer preference
• Limitation in the ability to predict eating quality
• Limited consumer understanding of the system
Selection/ Prediction challenges
• Programs to improve eating quality
• Ability to better predict the eating quality
level for market purposes
Increase consumer’s confidence that
quality expectations are met
Higher
quality
grade
= more
tender and
palatable
meat
Higher
quality
grade
= more
tender and
palatable
meat
11. Sample Collection and Preparation
•Rib sections:
• Transported to ISU Meat
Laboratory, or shipped from
California to OSU
• Fabricated into steaks
• Frozen at 14d postmortem
12. Warner-Bratzler Shear Force (WBSF)
•Broiled on impingement oven
at 200⁰C to internal temperature
of 68⁰C
•Cooled at 4⁰C for 18-24 h
•Six 1.27 cm cores removed and sheared
•Average peak load (kg) was analyzed
13. Sensory Panels
•Cooked similarly to steaks for WBS
•Sessions conducted once or twice per day
•12 samples served randomly to panelists
•Served to eight member trained panel
8 trained panelistsEach steak
Average
score of
all
panelists
14. Sensory Panel Evaluation
•Evaluated juiciness, tenderness, flavor
•Juiciness – 8 point scale (1 = extremely dry and 8
= extremely juicy)
•Tenderness – 8 point scale (1 = extremely tough
and 8 = extremely tender)
•Connective Tissue – 8 point scale (1 = abundant
and 8 = none)
•Beef, Painty/Fishy, and Livery/Metallic Flavors – 3
point scale (1 = not detectable, 2 = slightly
detectable, and 3 = strong)
20. GWAS for WBSF - SVS
•Mixed Model GWAS using a single locus
(EMMAX) and multi-locus models (MLMM)
• Genomic relationship matrix
• Contemporary groups
22. GWAS for WBSF - SVS
•Mixed Model GWAS using a single locus (EMMAX)
• Genomic relationship matrix
• Contemporary groups
Samples scanned: 2,076
Markers scanned: 51,218
Markers analyzed: 51,141
Pseudo-heritability: 0.37
31. Genomic Prediction
•Accuracy of DGV - key to successful application
of genomic selection
•Cross validation - assess performance of
prediction
•SVS: five-fold cross-validation for evaluation of
predictive performance of GBLUP/BayesC for
WBSF
34. Accuracy of gEBV
•Genetic correlation between gEBV and
phenotype.
• Bivariate animal model in Wombat
Accuracy:
0.59
35. Palatability of Beef - goals
Genome-wide association (GWAS)11
GWAS signals underlying biology33
Genomic Prediction22
36. •8-10 individual traits
(sub-phenotypes):
• 50,000 SNP effects for each one on >2,000 animals
•Systems biology: integration of data sets
• Holistic view of the system – key players can
emerge
Palatability trait
Gene network theory: use SNP association data
to guide the inference of gene regulatory networks
Association Weight Matrix (Fortes 2010)
multivariate view of GWAS using PCIT (partial correlation
and information theory Reverter & Chan 2008)
37. Network Analysis (Palatability)
All Phenotypes (10 total) + 54k SNPs
Select top SNPs based on WBSF
Matrix of SNP effects (-log10pvalue)
100 SNP by 10 traits
SVS EMMAX
PCIT
• Partial Correlation Information Theory (Reverter and Chan, 2008)
SNP SNP
SNP
• Significant SNPs correlated among
multiple sub-phenotypes are
important for regulating the overall
phenotype
• Optimized to handle SNPs and
genomic windows
38. Network Analysis (Palatability)
All Phenotypes (10 total) + 54k SNPs
Select top SNPs based on WBSF
Matrix of SNP effects (-log10pvalue)
100 SNP by 10 traits
Direct and partial correlations among 100 SNPs
ENSEMBL annotation of 100 SNPs
SNPs ~ 2,500 bp of a gene
SNPs in genes
+
SNPs not in genes
?
SVS EMMAX
PCIT
DAVID enrichment
analysis
Gene cluster scoring
GO/Biol. Process definitions
KEGG Pathway Analysis
Cytoscape
correlation network
• Networking and
Clustering
•Direct correlations
visualized in
Cytoscape
•Clustering analysis -
MCODE - highly
connected genes
•Enriched GO terms
were identified
using
DAVID and
visualized using
REViGO
40. SAPS3: modulates
protein phosphatase
catalytic subunits
CAPN1: modulates
proteolysis of cytoskeletal
remodeling and signal
transduction.
CHI3L2: Involved in
cartilage biogenesis.
CA10: Catalyzes
reversible hydration of
carbon dioxide in various
processes.
GPHN: Involved in
membrane protein-
cytoskeleton interactions.
41. Conclusions
•Palatability or eating satisfaction - important for
the long-term sustainability of beef industry
•Collection of palatability phenotypes on large
numbers of animals is still problematic
• Findings focused on QTL detection rather than
genomic prediction
•New methods and approaches to move from
SNP signals closer to functional variants
42. Department of Animal
Science, OSU
Department of Animal
Science, OSU
• Justin Buchanan
• Deb VanOverbeke
• Gretchen Hilton
• Andrea Sexten
• Andrea Garmyn
• Lindsay King
• Jessica Neal
• Connie Underwood
Financial SupportFinancial Support
• Zoetis Animal Genetics
• OSU TIP FY08
• Florida Beef Council
Acknowledgments
Iowa State UniversityIowa State University
• Jim Reecy
• Dorian Garrick
• James Koltes
• Mahdi Saatchi
• Don Beitz
• Richard Tait
University of FloridaUniversity of Florida
• Mauricio Elzo
• Dwain Johnson
• Mesfin Gobena
USDA - MARCUSDA - MARC
• John Pollak
