Presentation on applications of genomic information in additional to estimation of breeding values made to the Department of Animal Science at North Carolina State University at 2010.
Zinc finger nucleases (ZFNs) are artificial proteins used to edit genes. They contain zinc finger peptides that recognize DNA sequences and nuclease domains that cut DNA. The objective of this study was to generate mastitis-resistant cows using ZFNs. Researchers used ZFNs to insert the human lysozyme gene into the beta-casein locus of bovine cells. The modified cells were used in nuclear transfer to produce cloned cows that secreted human lysozyme in their milk, enhancing resistance to bacterial infection. The results demonstrated that ZFNs can successfully and precisely edit the bovine genome to produce transgenic livestock with improved traits.
The document summarizes experiments studying the movement and directionality of the FtsK translocase protein on DNA molecules. Key findings include:
1) FtsK moves rapidly at 5 kilobases per second and can work against forces up to 60 piconewtons.
2) FtsK forms loops of DNA as it translocates and can reverse direction without dissociating from DNA.
3) When bound to lambda DNA, FtsK consistently moved in the same direction, toward the terminus region as predicted, even when the DNA was inverted.
Louis Stodieck, BioServe Space Technologies, University of Colorado at Boulder: "AMGEN Countermeasures for Bone and Muscle Loss in Space and on Earth." Presented at the 2013 International Space Station Research and Development Conference, http://www.astronautical.org/issrdc/2013.
Knockout mice are genetically engineered mice that have had one or more of their genes made defective or inactivated through genetic manipulation. This allows researchers to study the effects of removing or altering the function of a gene. Some examples of knockout mice used in disease modeling include models of cancer, heart disease, and diabetes. Specifically, mice with knocked out insulin receptors in muscles, fat, and liver tissues show defects that mimic diabetes in humans. Knockout mice are a valuable tool for disease research and drug testing due to similarities between mouse and human genes.
Neuromics Bases 2 and 3 Cell Based AssaysPete Shuster
This document provides information on cell-based assay solutions from Neuromics for drug discovery applications. It describes 3D blood-brain barrier models, extracellular matrixes, coating solutions, and published data from human BBB models. Details are given on human brain astrocytes and endothelial cells, as well as retinal cells. An example is shown of researchers using these cell types to create an in vitro BBB model. The document also discusses FBS and other serum options and provides contact information for Neuromics.
Bone is a dynamic tissue that is continuously renewed through the process of bone remodeling. This process is carried out by basic multicellular units containing osteoclasts, which resorb bone, and osteoblasts, which form new bone. A normal bone remodeling cycle maintains bone mass and quality through a balanced relationship between bone resorption and formation. Dysfunctions in osteoclasts or osteoblasts can disrupt this balance and lead to metabolic bone diseases characterized by either high or low bone turnover.
Zinc finger nucleases (ZFNs) are artificial proteins used to edit genes. They contain zinc finger peptides that recognize DNA sequences and nuclease domains that cut DNA. The objective of this study was to generate mastitis-resistant cows using ZFNs. Researchers used ZFNs to insert the human lysozyme gene into the beta-casein locus of bovine cells. The modified cells were used in nuclear transfer to produce cloned cows that secreted human lysozyme in their milk, enhancing resistance to bacterial infection. The results demonstrated that ZFNs can successfully and precisely edit the bovine genome to produce transgenic livestock with improved traits.
The document summarizes experiments studying the movement and directionality of the FtsK translocase protein on DNA molecules. Key findings include:
1) FtsK moves rapidly at 5 kilobases per second and can work against forces up to 60 piconewtons.
2) FtsK forms loops of DNA as it translocates and can reverse direction without dissociating from DNA.
3) When bound to lambda DNA, FtsK consistently moved in the same direction, toward the terminus region as predicted, even when the DNA was inverted.
Louis Stodieck, BioServe Space Technologies, University of Colorado at Boulder: "AMGEN Countermeasures for Bone and Muscle Loss in Space and on Earth." Presented at the 2013 International Space Station Research and Development Conference, http://www.astronautical.org/issrdc/2013.
Knockout mice are genetically engineered mice that have had one or more of their genes made defective or inactivated through genetic manipulation. This allows researchers to study the effects of removing or altering the function of a gene. Some examples of knockout mice used in disease modeling include models of cancer, heart disease, and diabetes. Specifically, mice with knocked out insulin receptors in muscles, fat, and liver tissues show defects that mimic diabetes in humans. Knockout mice are a valuable tool for disease research and drug testing due to similarities between mouse and human genes.
Neuromics Bases 2 and 3 Cell Based AssaysPete Shuster
This document provides information on cell-based assay solutions from Neuromics for drug discovery applications. It describes 3D blood-brain barrier models, extracellular matrixes, coating solutions, and published data from human BBB models. Details are given on human brain astrocytes and endothelial cells, as well as retinal cells. An example is shown of researchers using these cell types to create an in vitro BBB model. The document also discusses FBS and other serum options and provides contact information for Neuromics.
Bone is a dynamic tissue that is continuously renewed through the process of bone remodeling. This process is carried out by basic multicellular units containing osteoclasts, which resorb bone, and osteoblasts, which form new bone. A normal bone remodeling cycle maintains bone mass and quality through a balanced relationship between bone resorption and formation. Dysfunctions in osteoclasts or osteoblasts can disrupt this balance and lead to metabolic bone diseases characterized by either high or low bone turnover.
This study characterized osteoclast precursors in the mouse periosteum. Mice expressing a form of Cbl that abrogates its interaction with PI3K (YF mice) were compared to wild-type mice. The YF mice showed a 2.7-fold increase in mononuclear TRAP+ cells in the periosteum compared to wild-type mice. There was also an increasing trend in the number of EGFP+ cells in the trabecular bone and periosteum of YF mice. Further work is needed to determine if the EGFP+ cells are osteoclast precursors by staining with markers for monocyte/macrophage lineage cells and fluorescent TRAP staining.
1. The document discusses bone metabolism and prostate cancer, describing how factors like RANK ligand and osteoprotegerin regulate the balance between bone formation and resorption.
2. It summarizes a clinical trial comparing denosumab, a RANK ligand inhibitor, to zoledronic acid for treating bone metastases in prostate cancer patients. Denosumab delayed time to first skeletal-related event compared to zoledronic acid and reduced risk of multiple events.
3. Rates of adverse events were generally similar between the treatments, though denosumab resulted in fewer acute phase reactions and more cases of osteonecrosis of the jaw compared to zoledronic acid.
The document discusses research on using mechanostimulated Wharton's jelly stem cells seeded into human umbilical veins for tendon tissue engineering applications. Previous research found that seeding rat mesenchymal stem cells into human umbilical veins and applying mechanical stimulation improved the constructs' biomechanical properties and cellularity over static controls. The current research seeds human Wharton's jelly stem cells into umbilical veins and applies varying frequencies and durations of mechanical stimulation. Preliminary results found tenomodulin expression increased with stimulation, and collagen I expression increased most with less rigorous stimulation. Lower seeding densities and addition of growth factors may further improve the constructs for tendon tissue engineering.
The document summarizes research on identifying genetic risk factors for alopecia areata. It describes analyzing genetic data from over 700 patients to identify 64 candidate genes and 701 variants potentially involved in monogenic causes. Pathway analysis found these genes enriched for extracellular matrix functions. Further studies will validate co-segregation of variants in families and test for genetic burden using exome data from 10,000 controls. The research aims to elucidate pathogenesis by studying extracellular matrix integrity and signaling in patient samples.
Extreme fetal growth, either restricted (IUGR) or large (LGA), is associated with epigenetic changes in hematopoietic stem/progenitor cells that may increase risk of adult diseases. The study found global shifts towards DNA hypermethylation in these cells from infants with IUGR or LGA compared to controls. There was a sexually dimorphic response, with IUGR associated with greater epigenetic dysregulation in males and LGA predominantly affecting females. The differentially methylated loci were enriched near genes involved in glucose homeostasis and stem cell function.
The document lists the top 200 drugs by worldwide sales in 2013 according to data from IMS Health. The top selling drug was Adalimumab (Humira) with sales of $10.058 billion, which is a monoclonal antibody used to treat inflammatory diseases. Several other monoclonal antibodies, insulin analogues, and drugs for conditions like high cholesterol and cancer rounded out the top 20 drugs. The document provides each drug's generic name, brand name, main therapeutic class and worldwide sales.
Long-term space travel affects astronauts' health through various stressors that can impact their microbiome. The study aimed to characterize changes in astronauts' gut, oral, skin, and nose microbiomes during 6-12 month ISS missions. It found reductions in diversity and associations between microbiome changes and immune markers. Interactions were also observed between astronauts' skin microbiome and ISS environmental microbes. Metagenomic analysis indicated changes in GI microbial metabolic pathways, though not major shifts in short-chain fatty acid or vitamin production genes. The results further understanding of space travel's effects on astronaut health via microbiome alterations.
This study examined the androgenic effects of three progestagens (norethisterone, uterogestan, and medroxyprogesterone acetate) on bone density in castrated male mice. The progestagens were administered to castrated mice for 3 months. Bone density, ash weight, and mineral content were measured in the tibia. Kidney and seminal vesicle weights were also examined. Only norethisterone showed a slight but statistically significant increase in bone density compared to castrated mice. The other progestagens and castration had no effect on bone density, ash weight, mineral content, kidney weight, or seminal vesicle weight. This suggests that only norethisterone has
This document provides biographical and professional details about Derek J. Milner, including his education, research experience, teaching experience, awards, publications, and presentations. It outlines his educational background, including a Ph.D. in Molecular and Cellular Biology from Baylor College of Medicine and a B.S. in Biochemistry from the University of Iowa. It then details his extensive research experience in regenerative biology and tissue engineering at the University of Illinois over the past 15 years, focusing on projects involving muscle regeneration, stem cells, and animal models of bone and cartilage repair.
Jeffrey J. Whyte is a researcher who has published extensively on topics related to swine genetics, cloning, and using pig models for human diseases. Some of his publications include studies looking at using zinc finger nucleases and CRISPR to genetically modify pigs, producing cloned knockout pig models, and investigating cytokines and placental development in pigs. He has also researched using pig models to study cardiovascular conditions in humans.
This document summarizes cell-based assay solutions from Neuromics and its partnership with UB Systems. It describes 3D cell-based assays including blood-brain barrier models and extracellular matrix hydrogels. It also provides details on various human brain cell types such as endothelial cells, astrocytes, and pericytes that can be used to build customized 3D brain models. Additionally, it mentions services offered like media filling and various cell culture reagents including fetal bovine serum in different grades.
The document discusses how gene therapy can be used to better understand and treat musculoskeletal disorders and injuries by promoting tissue regeneration through localized delivery of growth factors and cytokines. It outlines how viral and non-viral vectors can be used to introduce therapeutic genes into tissues to accelerate healing and reduce recovery time for conditions like fractures, osteoarthritis, tendon injuries, and muscular dystrophy.
This research article describes the generation of new mouse models of partial trisomy and monosomy of human chromosome 21. The models contain extra or missing copies of a 9.4 Mb region on mouse chromosome 16 that is syntenic to a region on human chromosome 21. Mice with an extra copy (trisomy model) showed impaired locomotion and increased muscle strength/mass, while mice missing a copy (monosomy model) showed the opposite phenotype. Gene expression analysis revealed that genes related to muscle energy metabolism and mitochondria were downregulated in the trisomy mice and upregulated in the monosomy mice. This correlated with changes in mitochondrial proliferation and function in skeletal muscle, providing insight into the muscle and locom
1) The document presents research on the anti-osteoporotic effects of Salvadora persica stick extract (SPE) in an estrogen-deficient rat model of osteoporosis.
2) Methods included administering SPE orally to ovariectomized (OVX) rats at various doses for 16 weeks, and measuring bone mineral density, biomechanical strength, and biochemical markers of bone turnover.
3) Results showed SPE increased bone mineral density and biomechanical strength in a dose-dependent manner, and reduced bone turnover, indicating a protective effect against osteoporosis in OVX rats.
Use of NGS to identify the causal variant associated with a complex phenotypeJohn B. Cole, Ph.D.
This document summarizes a presentation on using next generation sequencing to identify the causal variant associated with a complex phenotype like dystocia in cattle. It discusses selecting animals to sequence, the sequencing and analysis process, challenges in annotation and validation, and recent successes in identifying causal mutations for other traits in cattle. The presentation outlines using sequencing to investigate a quantitative trait locus for dystocia on chromosome 18 in cattle that affects traits like birth weight and gestation length. It describes analyzing sequence data to identify variants associated with predicted birth weight and discusses ongoing challenges in sequencing, analysis, and validating causal variants.
Poster - SULI Spring 2016 - Dziulko, AdamAdam Dziulko
This study investigated whether distant-acting limb enhancers besides the ZRS enhancer could activate Shh expression from ~1Mb away. CRISPR/Cas9 was used to generate mice with the ZRS replaced by three other limb enhancers: hs1109, mm1179, and hs72. hs1109 and mm1179 were able to rescue Shh expression like ZRS, but hs72 did not, resembling a ZRS knockout. However, hs72 activated Shh when placed nearby in a transgenic reporter, suggesting distance determines an enhancer's activity. Further experiments will test if surrounding tethering elements contribute to remote activity.
The hunt for a functional mutation affecting conformation and calving traits ...John B. Cole, Ph.D.
Presentation from the 10th WCGALP meeting in Vancouver describing our research to identify the causal variant associated with calving and conformation (body shape and size) traits in Holstein cattle.
- MicroCT scans and mechanical testing were performed on bone samples from HIV-positive mice, HIV-negative mice, and mice treated with the antiretroviral drug AZT.
- The results showed that HIV-positive mice had lower bone mass and thinner trabeculae compared to other groups, indicating greater bone resorption. AZT treatment did not significantly affect bone morphology.
- While ultimate load was lower for bones from HIV-positive mice compared to other groups, there were no major differences in stiffness or other mechanical properties between the groups. So HIV infection, but not AZT treatment, negatively impacted bone quantity but not quality/strength.
Genomic selection has been successful in the dairy cattle industry by increasing genetic progress. Several challenges remain, including pre-selection bias when young genotyped bulls are selected for further breeding before progeny testing, and developing across-breed genomic evaluations. While genomic selection is widely used and has increased the rate of genetic improvement, continuing work is needed to address these challenges to ensure the most accurate genomic evaluations.
This study characterized osteoclast precursors in the mouse periosteum. Mice expressing a form of Cbl that abrogates its interaction with PI3K (YF mice) were compared to wild-type mice. The YF mice showed a 2.7-fold increase in mononuclear TRAP+ cells in the periosteum compared to wild-type mice. There was also an increasing trend in the number of EGFP+ cells in the trabecular bone and periosteum of YF mice. Further work is needed to determine if the EGFP+ cells are osteoclast precursors by staining with markers for monocyte/macrophage lineage cells and fluorescent TRAP staining.
1. The document discusses bone metabolism and prostate cancer, describing how factors like RANK ligand and osteoprotegerin regulate the balance between bone formation and resorption.
2. It summarizes a clinical trial comparing denosumab, a RANK ligand inhibitor, to zoledronic acid for treating bone metastases in prostate cancer patients. Denosumab delayed time to first skeletal-related event compared to zoledronic acid and reduced risk of multiple events.
3. Rates of adverse events were generally similar between the treatments, though denosumab resulted in fewer acute phase reactions and more cases of osteonecrosis of the jaw compared to zoledronic acid.
The document discusses research on using mechanostimulated Wharton's jelly stem cells seeded into human umbilical veins for tendon tissue engineering applications. Previous research found that seeding rat mesenchymal stem cells into human umbilical veins and applying mechanical stimulation improved the constructs' biomechanical properties and cellularity over static controls. The current research seeds human Wharton's jelly stem cells into umbilical veins and applies varying frequencies and durations of mechanical stimulation. Preliminary results found tenomodulin expression increased with stimulation, and collagen I expression increased most with less rigorous stimulation. Lower seeding densities and addition of growth factors may further improve the constructs for tendon tissue engineering.
The document summarizes research on identifying genetic risk factors for alopecia areata. It describes analyzing genetic data from over 700 patients to identify 64 candidate genes and 701 variants potentially involved in monogenic causes. Pathway analysis found these genes enriched for extracellular matrix functions. Further studies will validate co-segregation of variants in families and test for genetic burden using exome data from 10,000 controls. The research aims to elucidate pathogenesis by studying extracellular matrix integrity and signaling in patient samples.
Extreme fetal growth, either restricted (IUGR) or large (LGA), is associated with epigenetic changes in hematopoietic stem/progenitor cells that may increase risk of adult diseases. The study found global shifts towards DNA hypermethylation in these cells from infants with IUGR or LGA compared to controls. There was a sexually dimorphic response, with IUGR associated with greater epigenetic dysregulation in males and LGA predominantly affecting females. The differentially methylated loci were enriched near genes involved in glucose homeostasis and stem cell function.
The document lists the top 200 drugs by worldwide sales in 2013 according to data from IMS Health. The top selling drug was Adalimumab (Humira) with sales of $10.058 billion, which is a monoclonal antibody used to treat inflammatory diseases. Several other monoclonal antibodies, insulin analogues, and drugs for conditions like high cholesterol and cancer rounded out the top 20 drugs. The document provides each drug's generic name, brand name, main therapeutic class and worldwide sales.
Long-term space travel affects astronauts' health through various stressors that can impact their microbiome. The study aimed to characterize changes in astronauts' gut, oral, skin, and nose microbiomes during 6-12 month ISS missions. It found reductions in diversity and associations between microbiome changes and immune markers. Interactions were also observed between astronauts' skin microbiome and ISS environmental microbes. Metagenomic analysis indicated changes in GI microbial metabolic pathways, though not major shifts in short-chain fatty acid or vitamin production genes. The results further understanding of space travel's effects on astronaut health via microbiome alterations.
This study examined the androgenic effects of three progestagens (norethisterone, uterogestan, and medroxyprogesterone acetate) on bone density in castrated male mice. The progestagens were administered to castrated mice for 3 months. Bone density, ash weight, and mineral content were measured in the tibia. Kidney and seminal vesicle weights were also examined. Only norethisterone showed a slight but statistically significant increase in bone density compared to castrated mice. The other progestagens and castration had no effect on bone density, ash weight, mineral content, kidney weight, or seminal vesicle weight. This suggests that only norethisterone has
This document provides biographical and professional details about Derek J. Milner, including his education, research experience, teaching experience, awards, publications, and presentations. It outlines his educational background, including a Ph.D. in Molecular and Cellular Biology from Baylor College of Medicine and a B.S. in Biochemistry from the University of Iowa. It then details his extensive research experience in regenerative biology and tissue engineering at the University of Illinois over the past 15 years, focusing on projects involving muscle regeneration, stem cells, and animal models of bone and cartilage repair.
Jeffrey J. Whyte is a researcher who has published extensively on topics related to swine genetics, cloning, and using pig models for human diseases. Some of his publications include studies looking at using zinc finger nucleases and CRISPR to genetically modify pigs, producing cloned knockout pig models, and investigating cytokines and placental development in pigs. He has also researched using pig models to study cardiovascular conditions in humans.
This document summarizes cell-based assay solutions from Neuromics and its partnership with UB Systems. It describes 3D cell-based assays including blood-brain barrier models and extracellular matrix hydrogels. It also provides details on various human brain cell types such as endothelial cells, astrocytes, and pericytes that can be used to build customized 3D brain models. Additionally, it mentions services offered like media filling and various cell culture reagents including fetal bovine serum in different grades.
The document discusses how gene therapy can be used to better understand and treat musculoskeletal disorders and injuries by promoting tissue regeneration through localized delivery of growth factors and cytokines. It outlines how viral and non-viral vectors can be used to introduce therapeutic genes into tissues to accelerate healing and reduce recovery time for conditions like fractures, osteoarthritis, tendon injuries, and muscular dystrophy.
This research article describes the generation of new mouse models of partial trisomy and monosomy of human chromosome 21. The models contain extra or missing copies of a 9.4 Mb region on mouse chromosome 16 that is syntenic to a region on human chromosome 21. Mice with an extra copy (trisomy model) showed impaired locomotion and increased muscle strength/mass, while mice missing a copy (monosomy model) showed the opposite phenotype. Gene expression analysis revealed that genes related to muscle energy metabolism and mitochondria were downregulated in the trisomy mice and upregulated in the monosomy mice. This correlated with changes in mitochondrial proliferation and function in skeletal muscle, providing insight into the muscle and locom
1) The document presents research on the anti-osteoporotic effects of Salvadora persica stick extract (SPE) in an estrogen-deficient rat model of osteoporosis.
2) Methods included administering SPE orally to ovariectomized (OVX) rats at various doses for 16 weeks, and measuring bone mineral density, biomechanical strength, and biochemical markers of bone turnover.
3) Results showed SPE increased bone mineral density and biomechanical strength in a dose-dependent manner, and reduced bone turnover, indicating a protective effect against osteoporosis in OVX rats.
Use of NGS to identify the causal variant associated with a complex phenotypeJohn B. Cole, Ph.D.
This document summarizes a presentation on using next generation sequencing to identify the causal variant associated with a complex phenotype like dystocia in cattle. It discusses selecting animals to sequence, the sequencing and analysis process, challenges in annotation and validation, and recent successes in identifying causal mutations for other traits in cattle. The presentation outlines using sequencing to investigate a quantitative trait locus for dystocia on chromosome 18 in cattle that affects traits like birth weight and gestation length. It describes analyzing sequence data to identify variants associated with predicted birth weight and discusses ongoing challenges in sequencing, analysis, and validating causal variants.
Poster - SULI Spring 2016 - Dziulko, AdamAdam Dziulko
This study investigated whether distant-acting limb enhancers besides the ZRS enhancer could activate Shh expression from ~1Mb away. CRISPR/Cas9 was used to generate mice with the ZRS replaced by three other limb enhancers: hs1109, mm1179, and hs72. hs1109 and mm1179 were able to rescue Shh expression like ZRS, but hs72 did not, resembling a ZRS knockout. However, hs72 activated Shh when placed nearby in a transgenic reporter, suggesting distance determines an enhancer's activity. Further experiments will test if surrounding tethering elements contribute to remote activity.
The hunt for a functional mutation affecting conformation and calving traits ...John B. Cole, Ph.D.
Presentation from the 10th WCGALP meeting in Vancouver describing our research to identify the causal variant associated with calving and conformation (body shape and size) traits in Holstein cattle.
- MicroCT scans and mechanical testing were performed on bone samples from HIV-positive mice, HIV-negative mice, and mice treated with the antiretroviral drug AZT.
- The results showed that HIV-positive mice had lower bone mass and thinner trabeculae compared to other groups, indicating greater bone resorption. AZT treatment did not significantly affect bone morphology.
- While ultimate load was lower for bones from HIV-positive mice compared to other groups, there were no major differences in stiffness or other mechanical properties between the groups. So HIV infection, but not AZT treatment, negatively impacted bone quantity but not quality/strength.
Genomic selection has been successful in the dairy cattle industry by increasing genetic progress. Several challenges remain, including pre-selection bias when young genotyped bulls are selected for further breeding before progeny testing, and developing across-breed genomic evaluations. While genomic selection is widely used and has increased the rate of genetic improvement, continuing work is needed to address these challenges to ensure the most accurate genomic evaluations.
This document summarizes John Cole's presentation on new genomic tools for dairy cattle. Some key points:
1) Genomic selection works well in dairy cattle due to extensive historical data, genetic evaluation programs, widespread AI use, and high-value animals. Genomics can reduce generation intervals.
2) Different genotyping arrays like BovineSNP50 and BovineHD are used, with over 300,000 animals genotyped as of 2013.
3) Genomic predictions provide information equivalent to dozens of progeny, improving reliability of selection, especially for lowly heritable traits. This allows more rapid genetic improvement.
Presentation describing how haplotypes can be used to make on-farm management decisions made at the 2012 European Association for Animal Production meeting in Bratislava.
What can your dog teach you about Genetics?rlanchantin
The following is a presentation to supplement a genetics class. The intention is to help build interest by showing dog breeding and how the scientific method has uncovered remarkable information about the morphological changes in dog breeds.
Discussion of latest work on simulating "evolve and resequence" experiments. Covers issues brought up by Burke et al.'s 2010 paper and how the simulations in Baldwin-Brown et al. (2014) address them.
LEO Commercialization: Space-based Research and Development and Manufacturing ISSRDC
This document discusses a panel discussion on commercializing space-based research and development and manufacturing. The panelists included the president of a company called iXpressGenes, an associate director from the National Center for Advancing Translational Sciences, and the president of Made In Space. The panel, moderated by a writer from Fast Company, focused on using the microgravity environment of low Earth orbit to conduct protein crystal growth for drug development, perform tissue-on-chip experiments to study human disease, and develop advanced manufacturing techniques. The goal is to utilize the International Space Station and find sustainable business opportunities to further space commercialization and translation.
Comparing the Amount and Quality of Information from Different Sequencing Str...jembrown
This document compares the amount and quality of phylogenetic information from six amniote phylogenomic datasets. It finds that while median support for major relationships is often strong, there is wide variance in support, both for and against known relationships. This suggests a minimum level of systematic error. Support for turtle placement varies the most between datasets, indicating relatively little phylogenetic information about turtles compared to other amniote groups. Overall, the analysis demonstrates that phylogenomic datasets can differ substantially in information content and reliability.
This document discusses using presence-absence variation (PAV) analysis to assess genome assemblies and identify foreign DNA. It describes the ScanPAV pipeline which extracts and analyzes PAV sequences between assemblies. The document provides examples of ScanPAV being used to evaluate human genome assemblies and identify contaminants in Tasmanian devil cancer genomes. Key findings include Mycoplasma and Streptococcus contamination identified in some devil cancer assemblies but no exogenous contribution found to the emergence of transmissible devil facial tumors.
Genetic gain on body composition in pigs by Computed Tomography (CT). Return ...Jørgen Kongsro
This document discusses using computed tomography (CT) to measure pigs' body composition for genetic selection. CT scanning allows accurate, non-invasive measurements of fat, muscle and bone in live animals. Using these CT measurements in breeding programs can increase genetic gain for important traits by around 30% compared to previous methods like chemical analysis or ultrasound. CT scanning has been used in Norwegian breeding programs since 2008, improving traits like lean meat percentage and intramuscular fat content while maintaining other important goals.
MALDI-TOF mass spectrometry was used to identify proteins in a mouse kidney tissue sample. Tissue slices were prepared using a washing and matrix sublimation process before analysis. Mass spectra identified peaks corresponding to G-protein, β-actin, and profilin by comparing m/z values to literature data. These proteins correlate with functions expected in kidney tissue like cell structure, migration, and signaling. Future work will involve digesting tissue to identify more proteins through peptide mass fingerprinting.
Big data biology for pythonistas: getting in on the genomics revolutionDarya Vanichkina
Slides for the talk I gave at PyCon Australia trying to simplify biology and genomics into something easily accessible for software developers and CompSci graduates.
I cover
1. What biological data looks like today
2. How the revolution in genomics sequencing technology is IN a hospital near you
3. How this is affecting patient treatment today
4. What are some of the major challenges in using this data in the clinic?
and ...
5. (1 slide about ) How my research fits into the paradigm of understanding human genetic variation.
Genetic architecture of developmental traits in populations of male gypsy mothscfriedline
This document summarizes a study on the genetic architecture of developmental traits in gypsy moth populations. The study established 7 gypsy moth populations in common gardens and sequenced 188 individuals to identify 11,021 SNPs. Three phenotypes - pupal duration, mass, and total development time - were measured. Population structure was corrected using PCA. Several SNPs were significantly associated with each trait, though effect sizes were small. Multilocus models explained over 50% of trait variation. Future work could involve refining the genome assembly and studying additional populations to detect smaller genetic effects.
Kidney and Urinary Pathways Knowledge Base (part of e-LICO)robertstevens65
1. The document describes a kidney and urinary pathway knowledge base (KUP KB) that integrates various types of biological data using semantic web technologies.
2. The KUP KB aims to provide background knowledge for data mining experiments and act as a collaborative repository for kidney and urinary pathway data.
3. An ontology is being developed to represent the kidney and urinary pathway domain and enable querying across the integrated data sources in the KUP KB.
This document summarizes the Wheat Genome Project. It discusses:
1) The goals of the project which are to lay a foundation to accelerate wheat improvement and increase profitability throughout the industry.
2) The current status of the project which has sequenced and assembled 40 chromosome arms totaling 10.2 Gb and annotated over 124,000 genes.
3) Future applications of the project resources which will include high density SNP chips, analyses of wheat genome evolution and gene expression, and facilitating map-based cloning of important wheat genes.
YEAR IN REVIEW - Genetics, Genomics, EpigeneticsOARSI
- Two large genome-wide association studies identified 57 new genetic risk loci for osteoarthritis, almost tripling the total number known from 33 to 90.
- Studies of hip shape and developmental hip disorders found that some osteoarthritis genetic variants influence hip morphology during development.
- New genomic techniques including single-cell RNA sequencing of cartilage and ATAC sequencing to map open chromatin identified cell types and regulatory regions in osteoarthritis.
- Epigenetic studies profiled long non-coding RNAs, microRNAs, and histone modifications in osteoarthritis cartilage to characterize the epigenetic landscape.
Presentation delivered by Dr. Jesse Poland (Kansas State University, USA) at Borlaug Summit on Wheat for Food Security. March 25 - 28, 2014, Ciudad Obregon, Mexico.
http://www.borlaug100.org
1. Dr. Madhuri Hegde presented on detecting small intragenic deletions using targeted comparative genomic hybridization (aCGH).
2. She discussed several examples of deletions less than 2.5 kb detected by aCGH in disease genes including PAH, STK11, HPRT1, and EMD.
3. She concluded that aCGH is a valuable tool for detecting small intragenic deletions and providing insights into deletion mechanisms.
Similar to What can we do with dairy cattle genomics other than predict more accurate breeding values? (20)
The national genetic evaluation program
for dairy cattle in the United States is described. Topics include an historical overview of traits and statistical methodology, the structure of the contemporary dairy genetics industry, and the implementation of genomic selection.
Using genotypes to construct phenotypes for dairy cattle breeding programs an...John B. Cole, Ph.D.
Modern dairying uses sophisticated data collection systems to maximize farm profitability. This has traditionally included information on cows and their environments, and now commonly includes genotype information from high-density single nucleotide polymorphism (SNP) panels. The US national database alone contains genotypes for 924,543 bulls and cows as of March 23, 2015, and many other countries are also genotyping animals. As the data continue to grow, the prospect of using genotypes to construct phenotypes directly, instead of measuring phenotypes on animals, becomes more attractive. There are many applications for this genomic information other than the prediction of breeding values. A notable recent application is the use of haplotypes in combination with next-generation sequencing data to identify causal variants associated with recessives. The methodology for identifying recessive haplotypes by searching for a deficit of homozygotes was first used in combination with sequence data to identify the causal variant (APAF1) associated with the HH1 haplotype. The US currently tracks 24 recessive haplotypes in four cattle breeds, and thanks to the work of several teams around the world the causal variants for 17 of them are known. The haplotypes include lethal recessive conditions, such as brachyspina, as well as hair coat color and polledness. There is growing interest in the latter to improve animal welfare and increase economic efficiency, but the polled haplotype has a very low frequency (0.41%, 0.93%, and 2.22% in Brown Swiss, Holstein, and Jersey, respectively). Increasing haplotype frequency by index selection requires known status for all animals. Gene content (GC) for non-genotyped animals was computed using records from genotyped relatives. Prediction accuracy was checked by comparing polled status from recessive codes and animal names to GC for 1,615 non-genotyped Jerseys with known status. 97% (n = 675) of horned animals were correctly assigned GC near 0, and 3% (n = 19) were assigned GC near 1. Heterozygous polled animals had GC near 0 (52%, n = 474) and near 1 (47%; n = 433), although 3 animals were assigned a GC near 2. All homozygous polled animals (n = 11) were assigned GC near 2. Genotype information can also be combined with other data, such as milk spectral data, to predict phenotypes for traits that are expensive or difficult to measure directly. These data can be used for precision farm management, including early culling decisions, monitoring of animals at risk for health problems, and identification of efficient and inefficient cows. The most substantial challenge faced by many dairy managers will be the effective use of the new phenotypes that now are available.
This presentation describes recent changes to the national genetic evaluation system, as well as new research undertaken by AGIL scientists. Topics covered include the 2014 genetic base change, updates to the lifetime net merit selection index, and introduction of the grazing merit index, and the redefinition of daughter pregnancy rate. New research on the use of gene content to predict polled status, and statistical models for accommodating genotype-by-environment interactions also are described.
If we would see further than others: research & technology today and tomorrowJohn B. Cole, Ph.D.
The document discusses the use of technology on dairy farms. It notes that technology provides benefits like making work faster, cheaper, and easier. It then discusses several technologies used on dairy farms today like automated systems for measuring feed and water intake, monitoring cows, and milking systems. The document also looks at challenges like the need for more frequent milk sampling and how collected on-farm data is not always put in a central database. It concludes that sensor technology is producing large amounts of data that could improve management if combined across farms.
Using genotyping and whole-genome sequencing to identify causal variants asso...John B. Cole, Ph.D.
Talk on identification of causal variants given to graduate students at the Universidade Federal de Viçosa in Viçosa, MG, Brasil, on September 9, 2014. It discusses work in my lab to identify causal variants associated with simple and complex modes of inheritance using SNP genotyping and next generation sequencing.
Talk on the genetic and genomic evaluation system for US dairy cattle made to scientists at Embrapa Gado de Leite in Juiz de Fora, MG, Brasil, on September 10, 2014.
An updated version of lifetime net merit incorporating additional fertility t...John B. Cole, Ph.D.
The slides for my upcoming talk on the 2014 revision of the lifetime net merit selection index to be presented at the 2014 ASAS-ADSA-CSAS Joint Annual Meeting in Kansas City, MO.
Genetic Evaluation of Stillbirth in US Holsteins Using a Sire-maternal Grands...John B. Cole, Ph.D.
This document summarizes the genetic evaluation of stillbirth in US Holsteins using a sire-maternal grandsire threshold model. Over 6 million stillbirth records from 1980-2005 were analyzed. Heritability of direct and maternal stillbirth was estimated to be 3.0% and 6.5%, respectively. Genetic and phenotypic trends for stillbirth over time were small. Stillbirth EPDs were included in the US National Milk Progeny Test program starting in August 2006 and the US began participating in Interbull evaluations for calving traits in November 2006.
Opportunities for genetic improvement of health and fitness traitsJohn B. Cole, Ph.D.
This document summarizes a presentation on opportunities for genetic improvement of health and fitness traits in dairy cattle. It discusses challenges such as low heritability of health traits and lack of standardized recording. It also provides examples of ways to increase genetic gain, such as improving reliability through genomics and increasing selection intensity. International efforts to develop guidelines for recording health traits are described. Overall, the presentation argues that improving health and fitness should be a priority for the dairy industry given economic impacts, and that genetic selection can help achieve improvements provided data recording is expanded and standardized.
Genomic selection and systems biology – lessons from dairy cattle breedingJohn B. Cole, Ph.D.
Presentation made to the staff of Keygene, NV, in Wageningen, The Netherlands.
(I don't know what the problem is with the template here. It looks fine if you use a dark background.)
This document summarizes research on genomic evaluation of dairy cattle health traits. It discusses challenges in evaluating health traits including low heritability and inconsistent definitions. The researchers conducted single and multiple trait genetic and genomic analyses on health event data from over 1 million US dairy cow records. Heritability estimates for various health events ranged from 0.03 to 0.20. Genomic evaluation allowed more accurate prediction of sires' daughters' probabilities of different health events compared to traditional genetic evaluation. The multiple trait genomic analysis found moderate to strong genetic correlations between some health events.
The use and economic value of genomic testing for calves on dairy farmsJohn B. Cole, Ph.D.
This document discusses the use and economic value of genomic testing for calves on dairy farms. It provides information on how genomic selection works and how it can increase genetic gain. Genomic testing can be used for animal identification and parentage verification, early culling decisions, mate selection to produce better calves, and identifying elite cows. The document examines studies that show dairy farms could make improved mating decisions using genomic testing data to pair cows and bulls. Genomic testing provides reliable estimates of animals' genetic merit and can help farmers make better long-term breeding and management decisions.
Genomic evaluation of low-heritability traits: dairy cattle health as a modelJohn B. Cole, Ph.D.
Genetic selection has been very successful when applied to traits of moderate to high heritability, but progress has been slow for traits with low heritabilities. The problem is further compounded when novel traits are considered because data needed to calculate high-reliability PTA generally are not available. A combination of producer-recorded health event data and SNP genotypes may permit the routine calculation of PTA with reasonable reliabilities for health traits.
Poster presented at the 5th International Symposium on Animal Functional Genetics in Guaruja, Brazil, in 2014.
New applications of genomic technology in the US dairy industryJohn B. Cole, Ph.D.
John B. Cole presented on new applications of genomic technology in the US dairy industry. Some key points include: genomic selection has been successful due to extensive historical data and widespread use of AI; over 300,000 animals have been genotyped across several dairy breeds; the percentage of genomically tested young bulls marketed has increased significantly since 2007; non-additive effects, novel recessives, and whole genome sequencing can further improve selection; and new phenotypes like health traits and methane production are being studied but require large datasets for accurate evaluation.
PyPedal, an open source software package for pedigree analysisJohn B. Cole, Ph.D.
PyPedal is an open source package written in the Python programming language that provides high-level tools for manipulating pedigrees. The goal is to provide expressive tools for exploratory data analysis. This was a poster presented at the 2012 European Association for Animal Production meeting in Bratislava.
This document summarizes research using high-density SNP genotypes to fine-map quantitative trait loci (QTL) in cattle. It describes Illumina genotyping arrays with varying numbers of SNPs, from 54k to 778k. Two examples are given of identifying causal variants for haplotypes related to fertility. For HH1 in Holsteins, sequencing identified a missense mutation in APAF1 associated with embryonic lethality. For JH1 in Jerseys, a stopgain mutation was found in CWC15. Preliminary fine-mapping of the Weaver locus using HD genotypes identified a region on BTA4 for further study by next-generation sequencing.
Immersive Learning That Works: Research Grounding and Paths ForwardLeonel Morgado
We will metaverse into the essence of immersive learning, into its three dimensions and conceptual models. This approach encompasses elements from teaching methodologies to social involvement, through organizational concerns and technologies. Challenging the perception of learning as knowledge transfer, we introduce a 'Uses, Practices & Strategies' model operationalized by the 'Immersive Learning Brain' and ‘Immersion Cube’ frameworks. This approach offers a comprehensive guide through the intricacies of immersive educational experiences and spotlighting research frontiers, along the immersion dimensions of system, narrative, and agency. Our discourse extends to stakeholders beyond the academic sphere, addressing the interests of technologists, instructional designers, and policymakers. We span various contexts, from formal education to organizational transformation to the new horizon of an AI-pervasive society. This keynote aims to unite the iLRN community in a collaborative journey towards a future where immersive learning research and practice coalesce, paving the way for innovative educational research and practice landscapes.
Remote Sensing and Computational, Evolutionary, Supercomputing, and Intellige...University of Maribor
Slides from talk:
Aleš Zamuda: Remote Sensing and Computational, Evolutionary, Supercomputing, and Intelligent Systems.
11th International Conference on Electrical, Electronics and Computer Engineering (IcETRAN), Niš, 3-6 June 2024
Inter-Society Networking Panel GRSS/MTT-S/CIS Panel Session: Promoting Connection and Cooperation
https://www.etran.rs/2024/en/home-english/
The binding of cosmological structures by massless topological defectsSérgio Sacani
Assuming spherical symmetry and weak field, it is shown that if one solves the Poisson equation or the Einstein field
equations sourced by a topological defect, i.e. a singularity of a very specific form, the result is a localized gravitational
field capable of driving flat rotation (i.e. Keplerian circular orbits at a constant speed for all radii) of test masses on a thin
spherical shell without any underlying mass. Moreover, a large-scale structure which exploits this solution by assembling
concentrically a number of such topological defects can establish a flat stellar or galactic rotation curve, and can also deflect
light in the same manner as an equipotential (isothermal) sphere. Thus, the need for dark matter or modified gravity theory is
mitigated, at least in part.
Unlocking the mysteries of reproduction: Exploring fecundity and gonadosomati...AbdullaAlAsif1
The pygmy halfbeak Dermogenys colletei, is known for its viviparous nature, this presents an intriguing case of relatively low fecundity, raising questions about potential compensatory reproductive strategies employed by this species. Our study delves into the examination of fecundity and the Gonadosomatic Index (GSI) in the Pygmy Halfbeak, D. colletei (Meisner, 2001), an intriguing viviparous fish indigenous to Sarawak, Borneo. We hypothesize that the Pygmy halfbeak, D. colletei, may exhibit unique reproductive adaptations to offset its low fecundity, thus enhancing its survival and fitness. To address this, we conducted a comprehensive study utilizing 28 mature female specimens of D. colletei, carefully measuring fecundity and GSI to shed light on the reproductive adaptations of this species. Our findings reveal that D. colletei indeed exhibits low fecundity, with a mean of 16.76 ± 2.01, and a mean GSI of 12.83 ± 1.27, providing crucial insights into the reproductive mechanisms at play in this species. These results underscore the existence of unique reproductive strategies in D. colletei, enabling its adaptation and persistence in Borneo's diverse aquatic ecosystems, and call for further ecological research to elucidate these mechanisms. This study lends to a better understanding of viviparous fish in Borneo and contributes to the broader field of aquatic ecology, enhancing our knowledge of species adaptations to unique ecological challenges.
EWOCS-I: The catalog of X-ray sources in Westerlund 1 from the Extended Weste...Sérgio Sacani
Context. With a mass exceeding several 104 M⊙ and a rich and dense population of massive stars, supermassive young star clusters
represent the most massive star-forming environment that is dominated by the feedback from massive stars and gravitational interactions
among stars.
Aims. In this paper we present the Extended Westerlund 1 and 2 Open Clusters Survey (EWOCS) project, which aims to investigate
the influence of the starburst environment on the formation of stars and planets, and on the evolution of both low and high mass stars.
The primary targets of this project are Westerlund 1 and 2, the closest supermassive star clusters to the Sun.
Methods. The project is based primarily on recent observations conducted with the Chandra and JWST observatories. Specifically,
the Chandra survey of Westerlund 1 consists of 36 new ACIS-I observations, nearly co-pointed, for a total exposure time of 1 Msec.
Additionally, we included 8 archival Chandra/ACIS-S observations. This paper presents the resulting catalog of X-ray sources within
and around Westerlund 1. Sources were detected by combining various existing methods, and photon extraction and source validation
were carried out using the ACIS-Extract software.
Results. The EWOCS X-ray catalog comprises 5963 validated sources out of the 9420 initially provided to ACIS-Extract, reaching a
photon flux threshold of approximately 2 × 10−8 photons cm−2
s
−1
. The X-ray sources exhibit a highly concentrated spatial distribution,
with 1075 sources located within the central 1 arcmin. We have successfully detected X-ray emissions from 126 out of the 166 known
massive stars of the cluster, and we have collected over 71 000 photons from the magnetar CXO J164710.20-455217.
Describing and Interpreting an Immersive Learning Case with the Immersion Cub...Leonel Morgado
Current descriptions of immersive learning cases are often difficult or impossible to compare. This is due to a myriad of different options on what details to include, which aspects are relevant, and on the descriptive approaches employed. Also, these aspects often combine very specific details with more general guidelines or indicate intents and rationales without clarifying their implementation. In this paper we provide a method to describe immersive learning cases that is structured to enable comparisons, yet flexible enough to allow researchers and practitioners to decide which aspects to include. This method leverages a taxonomy that classifies educational aspects at three levels (uses, practices, and strategies) and then utilizes two frameworks, the Immersive Learning Brain and the Immersion Cube, to enable a structured description and interpretation of immersive learning cases. The method is then demonstrated on a published immersive learning case on training for wind turbine maintenance using virtual reality. Applying the method results in a structured artifact, the Immersive Learning Case Sheet, that tags the case with its proximal uses, practices, and strategies, and refines the free text case description to ensure that matching details are included. This contribution is thus a case description method in support of future comparative research of immersive learning cases. We then discuss how the resulting description and interpretation can be leveraged to change immersion learning cases, by enriching them (considering low-effort changes or additions) or innovating (exploring more challenging avenues of transformation). The method holds significant promise to support better-grounded research in immersive learning.
Sharlene Leurig - Enabling Onsite Water Use with Net Zero Water
What can we do with dairy cattle genomics other than predict more accurate breeding values?
1. John B. ColeJohn B. Cole
Animal Improvement Programs Laboratory
Agricultural Research Service, USDA
Beltsville, MD 20705-2350
john.cole@ars.usda.gov
What can we do with dairy cattle
genomics other than predict more
accurate breeding values?
2. NCSU, November 23, 2010 (2) Cole
Whole-genome selection (2008)
• Use many markers to track inheritance
of chromosomal segments
• Estimate the impact of each segment on
each trait
• Combine estimates with traditional
evaluations to produce genomic
evaluations (GPTA)
• Select animals shortly after birth using
GPTA
• Very successful worldwide
3. NCSU, November 23, 2010 (3) Cole
Data and evaluation flow
Animal
Improvement
Programs
Laboratory,
USDA
AI
organizations,
breed
associations
Dairy
producers
DNA
laboratories
samples
samples
samples
genotypes
nominations
evaluations
4. NCSU, November 23, 2010 (4) Cole
Reliabilities for young bulls
0
250
500
750
1000
1250
1500
0 10 20 30 40 50 60 70 80 90 100
Bulls(no.)
Protein reliability (%)
GPTATraditional
PA
5. NCSU, November 23, 2010 (5) Cole
Genotyping options
• Illumina
• Infinium: 3K, 50K, 770K SNP
• GoldenGate: 384 to 1,536 SNP
• Affymetrix
• High-density product (650K) expected
in late 2010/early 2011
• We can impute from lower to
higher densities with high accuracy
6. NCSU, November 23, 2010 (6) Cole
• Identify haplotypes in population
using many markers
• Track haplotypes with fewer markers
• e.g., use 5 SNP to track 25 SNP
• 5 SNP: 22020
• 25 SNP: 2022020002002002000202200
Imputation
7. NCSU, November 23, 2010 (7) Cole
• Whole-genome sequences on individuals
will be available in the next few years
•How will we store and use those data?
• Not feasible to calculate effects for
3,000,000,000 nucleotides
• Best application may be SNP discovery
What about whole-genome sequencing?
8. NCSU, November 23, 2010 (8) Cole
Materials
• 43,382 SNP from the Illumina BovineSNP50
• Genotypes from three breeds
• 1,455 Brown Swiss males and females
• 40,351 Holstein males and females
• 4,064 Jersey males and females
• Many phenotypes
• Yield (5)
• Health and fitness (7)
• Conformation (3 composites, 14-18 individual)
9. NCSU, November 23, 2010 (9) Cole
What else can we do with these data?
• Quantitative Genetics
• Validate theoretical predictions
• Understand genetic variation
• Functional Biology
• Fine-map recessives
• Relate phenotypes to genotypes
• Identify important genes in complex
systems
• Phylogeny
10. NCSU, November 23, 2010 (10) Cole
Predicted Mendelian sampling variance
Trait Breed Lower Expected Upper
DPR BS 0.09 1.45 1.57
HO 0.57 1.45 4.02
JE 0.09 0.98 1.27
Milk BS 35,335 215,168 507,076
HO 228,011 261,364 1,069,741
JE 150,076 205,440 601,979
NM$ BS 2,539 19,602 40,458
HO 16,601 19,602 87,449
JE 3,978 19,602 44,552
11. NCSU, November 23, 2010 (11) Cole
Predicted selection limits
Trait Breed Lower Upper Largest DGV
DPR BS 20 53 8
HO 40 139 8
JE 19 53 5
Milk BS 14,193 34,023 4,544
HO 24,883 77,923 7,996
JE 16,133 40,249 5,620
NM$ BS 3,857 9,140 1,102
HO 7,515 23,588 2,528
JE 4,678 11,517 1,556
12. NCSU, November 23, 2010 (12) Cole
How good a cow can we make in theory?
A “supercow” constructed from the best haplotypes in the
Holstein population would have an EBV(NM$) of $7,515
13. NCSU, November 23, 2010 (13) Cole
Genotype Parents and Grandparents
Manfred
O-Man
Jezebel
O-Style
Teamster
Deva
Dima
19. NCSU, November 23, 2010 (20) Cole
Fine-mapping Weavers
• 35,353 SNP on BTA4
• 69 Brown Swiss bulls with HD
genotypes
• 20 cases and 49 controls
• No affected animals!
• Microsatellite-mapped to the
interval 43.2–51.2 cM
21. NCSU, November 23, 2010 (22) Cole
Now what?
• We can’t find tissue from affected
animals…
• We could make embryos…
25%
ww
Ww WwX
50%
Ww
25%
WW Genotype
22. NCSU, November 23, 2010 (23) Cole
Dystocia Complex
• Markers on BTA 18 had the largest
effects for several traits:
• Dystocia and stillbirth: Sire and
daughter calving ease and sire
stillbirth
• Conformation: rump width, stature,
strength, and body depth
• Efficiency: longevity and net merit
• Large calves contribute to shorter
PL and decreased NM$
23. NCSU, November 23, 2010 (24) Cole
Marker Effects for Dystocia Complex
ARS-BFGL-NGS-109285
24. NCSU, November 23, 2010 (25) Cole
Refined Location Using HD Data
ARS-BFGL-NGS-109285
141 HO and 69 BS with 17,702 SNP on BTA18
25. NCSU, November 23, 2010 (26) Cole
Biology of the Dystocia Complex
• The key marker is ARS-BFGL-NGS-
109285 at 57,125,868 Mb on BTA18
• Located in a cluster of CD33-related
Siglec genes
• Many Siglecs involved in leptin signaling
• Preliminary results also indicate an
effect on gestation length
• Confirmed by Christian Maltecca
26. NCSU, November 23, 2010 (27) Cole
Correlations among GEBV for NM, PL, SCE,
DCE, STAT, STR, BDep, RWid
27. NCSU, November 23, 2010 (28) Cole
Discovery of Fertility Genes
Candidates for a fertility SNP chip
Potentially important in physiological causes of infertility
The Illumina GoldenGate Genotyping Assay
uses a discriminatory DNA polymerase and ligase to
interrogate 96, or from 384 to 1,536, SNP loci simultaneously.
Blastoff: +3.4 DPR
(=~13.6 days open)
Milk +793
28. NCSU, November 23, 2010 (29) Cole
Experimental Approach
Identify 384 proven bulls with accurate estimates of
DPR
Based on two runs of the Illumina Golden Gate genotyping system (96 samples per
run x 4 = 384)
CDDR: Historical bulls (all available bulls in top and bottom 10%) and current bulls
(randomly selected from > 3 and <-3)
192 High (> 2.7 DPR
192 Low (<-1.8 DPR)
Find 384 SNPs in genes controlling
reproduction
Genotype each bull for all 384 SNPs
Analyze the data to find relationships
29. NCSU, November 23, 2010 (30) Cole
How Were Fertility Markers Selected?
Candidates for a fertility SNP chip
Potentially important in physiological causes of infertility
Genes that are well known to be involved in reproduction
(LH, FSH, genes involves in prostaglandin synthesis,
etc)
Genes that are higher in embryos that are more likely to
establish pregnancy (i.e. genes found that are
differentially regulated by CSF2 and IGF1)
Genes in the literature that are expressed in the uterus
and have been related to embryo survival
(Schellander, Germany
30. NCSU, November 23, 2010 (31) Cole
BFGL-Illumina
Deep SNP Discovery
Angus
Holstein
Limousin
Jersey
Nelore
Brahman
Romagnola
Gir
BFGL
Genome Assemblies
Nelore
Water Buffalo
Pfizer
Light SNP Discovery
Angus
Holstein
Jersey
Hereford
Charolais
Simmental
Brahman
Waygu
Partners
Deep SNP Discovery
N’Dama
Sahiwal
Simmental
Hanwoo
Blonde d’Aquitaine
Montbeliard
31. NCSU, November 23, 2010 (32) Cole
• Collection of genotypes from universities and
public research organizations
• 3K genotypes from cooperator herds need to
enter the national dataset for reliable imputation
• Encourage even more widespread sharing of
genotypes across countries
• Funding of genotyping necessary to predict SNP
effects for future chips
• Intellectual property issues
Unresolved genotyping issues
32. NCSU, November 23, 2010 (33) Cole
33
iBMAC Consortium Funding
• USDA/NRI/CSREES
• 2006-35616-16697
• 2006-35205-16888
• 2006-35205-16701
• 2008-35205-04687
• 2009-65205-05635
• USDA/ARS
• 1265-31000-081D
• 1265-31000-090D
• 5438-31000-073D
• Merial
• Stewart Bauck
• NAAB
• Gordon Doak
• Accelerated Genetics
• ABS Global
• Alta Genetics
• CRI/Genex
• Select Sires
• Semex Alliance
• Taurus Service
• Illumina (industry)
• Marylinn Munson
• Cindy Lawley
• Diane Lince
• LuAnn Glaser
• Christian Haudenschild
• Beltsville (USDA-ARS)
• Curt Van Tassell
• Lakshmi Matukumalli
• Steve Schroeder
• Tad Sonstegard
• Univ Missouri (Land-Grant)
• Jerry Taylor
• Bob Schnabel
• Stephanie McKay
• Univ Alberta (University)
• Steve Moore
• Clay Center, NE (USDA-ARS)
• Tim Smith
• Mark Allan
• AIPL
• Paul VanRaden
• George Wiggans
• John Cole
• Leigh Walton
• Duane Norman
• BFGL
• Marcos de Silva
• Tad Sonstegard
• Curt Van Tassell
• University of Wisconsin
• Kent Weigel
• University of Maryland
School of Medicine
• Jeff O’Connell
• Partners
• GeneSeek
• DNA Landmarks
• Expression Analysis
• Genetic Visions
Implementation
Team
33. NCSU, November 23, 2010 (34) Cole
Conclusions
• To answer interesting questions we
need more data
• Genotypes AND phenotypes
• Big p, small n
• More complex methodology
• Can genomics be used to make better
on-farm decisions?
• Mate selection
• Identify animals susceptible to disease
• Pedigree discovery
Editor's Notes
We are all familiar with a traditional pedigree chart. Animal is expected to be an average of his parents.