Results of the BRD CAP project: progress toward identifying genetic markers associated with BRD susceptibility

2014 ◽  
Vol 15 (2) ◽  
pp. 157-160 ◽  
Author(s):  
Alison Van Eenennaam ◽  
Holly Neibergs ◽  
Christopher Seabury ◽  
Jeremy Taylor ◽  
Zeping Wang ◽  
...  
Keyword(s):  
Association Studies ◽  
Clinical Signs ◽  
The United States ◽  
Feedlot Cattle ◽  
United States Department ◽  
Genome Wide Association Studies ◽  
Dairy Calf ◽  
Definition Of ◽  
Genetic Evaluations ◽  
Quantitative Definition

AbstractThe Bovine Respiratory Disease Coordinated Agricultural Project (BRD CAP) is a 5-year project funded by the United States Department of Agriculture (USDA), with an overriding objective to use the tools of modern genomics to identify cattle that are less susceptible to BRD. To do this, two large genome wide association studies (GWAS) were conducted using a case:control design on preweaned Holstein dairy heifers and beef feedlot cattle. A health scoring system was used to identify BRD cases and controls. Heritability estimates for BRD susceptibility ranged from 19 to 21% in dairy calves to 29.2% in beef cattle when using numerical scores as a semi-quantitative definition of BRD. A GWAS analysis conducted on the dairy calf data showed that single nucleotide polymorphism (SNP) effects explained 20% of the variation in BRD incidence and 17–20% of the variation in clinical signs. These results represent a preliminary analysis of ongoing work to identify loci associated with BRD. Future work includes validation of the chromosomal regions and SNPs that have been identified as important for BRD susceptibility, fine mapping of chromosomes to identify causal SNPs, and integration of predictive markers for BRD susceptibility into genetic tests and national cattle genetic evaluations.

scholarly journals Characterization of Disease Resistance Loci in the USDA Soybean Germplasm Collection Using Genome-Wide Association Studies

2016 ◽  
Vol 106 (10) ◽  
pp. 1139-1151 ◽  
Author(s):  
Hao-Xun Chang ◽  
Alexander E. Lipka ◽  
Leslie L. Domier ◽  
Glen L. Hartman
Keyword(s):  
Disease Resistance ◽  
Association Studies ◽  
Germplasm Collection ◽  
The United States ◽  
Genome Wide Association ◽  
Bacterial Disease ◽  
United States Department ◽  
Genome Wide Association Studies ◽  
Soybean Germplasm ◽  
Genome Wide

Genetic resistance is a key strategy for disease management in soybean. Over the last 50 years, soybean germplasm has been phenotyped for resistance to many pathogens, resulting in the development of disease-resistant elite breeding lines and commercial cultivars. While biparental linkage mapping has been used to identify disease resistance loci, genome-wide association studies (GWAS) using high-density and high-quality markers such as single nucleotide polymorphisms (SNPs) has become a powerful tool to associate molecular markers and phenotypes. The objective of our study was to provide a comprehensive understanding of disease resistance in the United States Department of Agriculture Agricultural Research Service Soybean Germplasm Collection by using phenotypic data in the public Germplasm Resources Information Network and public SNP data (SoySNP50K). We identified SNPs significantly associated with disease ratings from one bacterial disease, five fungal diseases, two diseases caused by nematodes, and three viral diseases. We show that leucine-rich repeat (LRR) receptor-like kinases and nucleotide-binding site-LRR candidate resistance genes were enriched within the linkage disequilibrium regions of the significant SNPs. We review and present a global view of soybean resistance loci against multiple diseases and discuss the power and the challenges of using GWAS to discover disease resistance in soybean.

Abstract 439: Trajectory Analysis of Left Ventricular Dimensions From Biobank Data Uncovers Novel Genetic Associations

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Tess Pottinger ◽  
Megan J Puckelwartz ◽  
Lorenzo L Pesce ◽  
Anthony Gacita ◽  
Isabella Salamone ◽  
...  
Keyword(s):  
Heart Failure ◽  
Longitudinal Data ◽  
Association Studies ◽  
The United States ◽  
Left Ventricular ◽  
Genome Wide Association Studies ◽  
Qtc Interval ◽  
Regulatory Regions ◽  
Genome Wide ◽  
Over Time

Background: Approximately 6 million adults in the United States have heart failure. The progression of heart failure is variable arising from differences in sex, age, genetic background including ancestry, and medication response. Many population-based genetic studies of heart failure have been cross-sectional in nature, failing to gain additional power from longitudinal analyses. As heart failure is known to change over time, using longitudinal data trajectories as a quantitative trait will increase power in genome wide association studies (GWAS). Methods: We used the electronic health record in a racially and ethnically diverse medical biobank from a single, metropolitan US center. We used whole genome data from 896 unrelated participants analyzed, including 494 who had at least 1 electrocardiogram and 324 who had more than 1 echocardiogram (average of 3 observations per person). A mixture model based semiparametric latent growth curve model was used to cluster outcome measures used for genome-wide analyses. Results: GWAS on the trajectory probability of QTc interval identified significant associations with variants in regulatory regions proximal to the WLS gene, which encodes Wntless, a Wnt ligand secretion mediator. WLS was previously associated with QTc and myocardial infarction, thus confirming the power of the method. GWAS on the trajectory probability of left ventricular diameter (LVIDd) identified significant associations with variants in regulatory regions near MYO10 , which encodes unconventional Myosin-10. MYO10 was previously associated with obesity and metabolic syndrome. Conclusions: This is the first study to show an association with variants in or near MYO10 and left ventricular dimension changes over time. Further, we found that using trajectory probabilities can provide increased power to find novel associations with longitudinal data. This reduces the need for larger cohorts, and increases yield from smaller, well-phenotyped cohorts, such as those found in biobanks. This approach should be useful in the study of rare diseases and underrepresented populations.

Typical and atypical clinical signs and symptoms of myocardial infarction and delayed seeking of professional care among blacks

1997 ◽  
Vol 6 (1) ◽  
pp. 7-13 ◽  
Author(s):  
HO Lee
Keyword(s):  
Myocardial Infarction ◽  
Chest Pain ◽  
Clinical Signs ◽  
Signs And Symptoms ◽  
The United States ◽  
United States Department ◽  
Manual Search ◽  
Black Patients ◽  
Definitive Therapy ◽  
Clinical Signs And Symptoms

BACKGROUND: Despite the fact that the effectiveness of thrombolytic therapy for acute myocardial infarction is inversely related to the time between the onset of signs and symptoms and definitive therapy, long delays in seeking treatment have been reported consistently. A variety of reasons for the delays have been suggested. Because such delays are associated with longer hospital stays and higher mortality and morbidity, interventions that reduce delays are especially important. PURPOSE: To examine research on patients with myocardial infarction who delay seeking professional treatment and the factors related to the delay, and to review studies indicating that black patients have premonitory clinical signs and symptoms of myocardial infarction and changes in the structure and function of the cardiovascular system that are different from those in whites. METHODS: Studies were reviewed by using MEDLINE and by doing a manual search of relevant research journals in cardiovascular, nursing, and behavioral medicine published since 1970. Data published by the United States Department of Health and Human Services and the Agency for Health Care Policy and Research were also reviewed. RESULTS: Although the lengths of the delays have varied considerably, blacks have generally experienced longer delays than whites between acute onset of signs and symptoms of myocardial infarction and arrival at the emergency department. Studies show that black patients have a lower incidence of classic chest pain or discomfort but an increased incidence of dyspnea, whereas white patients are much more likely to complain of chest pain. CONCLUSION: Culturally sensitive public education about typical and atypical premonitory clinical signs and symptoms of myocardial infarction and the significance of early treatment of myocardial infarction in blacks is needed.

scholarly journals Fusarium Head Blight in Durum Wheat: Recent Status, Breeding Directions, and Future Research Prospects

2019 ◽  
Vol 109 (10) ◽  
pp. 1664-1675 ◽  
Author(s):  
Jemanesh K. Haile ◽  
Amidou N’Diaye ◽  
Sean Walkowiak ◽  
Kirby T. Nilsen ◽  
John M. Clarke ◽  
...  
Keyword(s):  
Durum Wheat ◽  
Fusarium Head Blight ◽  
Seed Quality ◽  
Association Studies ◽  
Tetraploid Wheat ◽  
The United States ◽  
Genome Wide Association Studies ◽  
Head Blight ◽  
Food And Feed ◽  
Fhb Resistance

Fusarium head blight (FHB) is a major fungal disease affecting wheat production worldwide. Since the early 1990s, FHB, caused primarily by Fusarium graminearum, has become one of the most significant diseases faced by wheat producers in Canada and the United States. The increasing FHB problem is likely due to the increased adoption of conservation tillage practices, expansion of maize production, use of susceptible wheat varieties in rotation, and climate variability. Durum wheat (Triticum turgidum sp. durum) is notorious for its extreme susceptibility to FHB and breeding for resistance is complicated because sources of FHB resistance are rare in the primary gene pool of tetraploid wheat. Losses due to this disease include yield, test weight, seed quality, food and feed quality, and when severe, market access. More importantly, it is the contamination with mycotoxins, such as deoxynivalenol, in Fusarium-infected durum kernels that causes the most serious economic as well as food and feed safety concerns. Several studies and thorough reviews have been published on germplasm development and breeding for FHB resistance and the genetics and genomics of FHB resistance in bread or common wheat (T. aestivum); however, similar reviews have not been conducted in durum wheat. Thus, the aim of this review is to summarize and discuss the recent research efforts to mitigate FHB in durum wheat, including quantitative trait locus mapping, genome-wide association studies, genomic prediction, mutagenesis and characterization of genes and pathways involved in FHB resistance. It also highlights future directions, FHB-resistant germplasm, and the potential role of morphological traits to enhance FHB resistance in durum wheat.

Neuroblastoma: A Tough Nut to Crack

2016 ◽  
pp. e548-e557 ◽  
Author(s):  
Frank Speleman ◽  
Julie R. Park ◽  
Tara O. Henderson
Keyword(s):  
Clinical Trials ◽  
Late Effects ◽  
Association Studies ◽  
Genomic Analysis ◽  
The United States ◽  
Malignant Neoplasms ◽  
Genome Wide Association Studies ◽  
Second Malignant Neoplasms ◽  
Tumor In Childhood

Neuroblastoma, an embryonal tumor arising from neural crest–derived progenitor cells, is the most common solid tumor in childhood, with more than 700 cases diagnosed per year in the United States. In the past several decades, significant advances have been made in the treatment of neuroblastoma. Treatment advances reflect improved understanding of the biology of neuroblastoma. Although amplification of MYCN was discovered in the early 1980s, our understanding of neuroblastoma oncogenesis has advanced in the last decade as a result of high-throughput genomic analysis, exome and whole-genome sequencing, genome-wide association studies, and synthetic lethal drug screens. Our refined understanding of neuroblastoma biology and genetics is reflected in improved prognostic stratification and appropriate tailoring of therapy in recent clinical trials. Moreover, for high-risk neuroblastoma, a disease that was uniformly fatal 3 decades ago, recent clinical trials incorporating autologous hematopoietic transplant and immunotherapy utilizing anti-GD2 antibody plus cytokines have shown improved event-free and overall survival. These advances have resulted in a growing population of long-term survivors of neuroblastoma. Examination of the late effects and second malignant neoplasms (SMNs) in both older generations of survivors and more recently treated survivors will inform both design of future trials and surveillance guidelines for long-term follow-up. As a consequence of advances in understanding of the biology of neuroblastoma, successful clinical trials, and refined understanding of the late effects and SMNs of survivors, the promise of precision medicine is becoming a reality for patients with neuroblastoma.

scholarly journals Coevolutionary Dynamics of Rice Blast Resistance Gene Pi-ta and Magnaporthe oryzae Avirulence Gene AVR-Pita 1

2016 ◽  
Vol 106 (7) ◽  
pp. 676-683 ◽  
Author(s):  
Yulin Jia ◽  
Erxun Zhou ◽  
Seonghee Lee ◽  
Tracy Bianco
Keyword(s):  
Magnaporthe Oryzae ◽  
Marker Assisted Selection ◽  
Defense Mechanism ◽  
Allelic Variation ◽  
Blast Resistance ◽  
Quantitative Resistance ◽  
Association Studies ◽  
The United States ◽  
Avirulence Gene ◽  
Genome Wide Association Studies

The Pi-ta gene in rice is effective in preventing infections by Magnaporthe oryzae strains that contain the corresponding avirulence gene, AVR-Pita1. Diverse haplotypes of AVR-Pita1 have been identified from isolates of M. oryzae from rice production areas in the United States and worldwide. DNA sequencing and mapping studies have revealed that AVR-Pita1 is highly unstable, while expression analysis and quantitative resistance loci mapping of the Pi-ta locus revealed complex evolutionary mechanisms of Pi-ta-mediated resistance. Among these studies, several Pi-ta transcripts were identified, most of which are probably derived from alternative splicing and exon skipping, which could produce functional resistance proteins that support a new concept of coevolution of Pi-ta and AVR-Pita1. User-friendly DNA markers for Pi-ta have been developed to support marker-assisted selection, and development of new rice varieties with the Pi-ta markers. Genome-wide association studies revealed a link between Pi-ta-mediated resistance and yield components suggesting that rice has evolved a complicated defense mechanism against the blast fungus. In this review, we detail the current understanding of Pi-ta allelic variation, its linkage with rice productivity, AVR-Pita allelic variation, and the coevolution of Pi-ta and AVR-Pita in Oryza species and M. oryzae populations, respectively. We also review the genetic and molecular basis of Pi-ta and AVR-Pita interaction, and its value in marker-assisted selection and engineering resistance.

scholarly journals Privacy-Preserving Data Sharing for Genome-Wide Association Studies

2013 ◽  
Vol 5 (1) ◽  
Author(s):  
Caroline Uhler ◽  
Aleksandra B. Slavkovic ◽  
Stephen E. Fienberg
Keyword(s):  
Differential Privacy ◽  
Association Studies ◽  
Simulated Data ◽  
Privacy Preserving ◽  
External Information ◽  
Genome Wide Association Studies ◽  
Chi Square ◽  
Gwas Study ◽  
Genome Wide ◽  
Definition Of

Traditional statistical methods for confidentiality protection of statistical databases do not scale well to deal with GWAS databases especially in terms of guarantees regarding protection from linkage to external information. The more recent concept of differential privacy, introduced by the cryptographic community, is an approach which provides a rigorous definition of privacy with meaningful privacy guarantees in the presence of arbitrary external information, although the guarantees may come at a serious price in terms of data utility. Building on such notions, we propose new methods to release aggregate GWAS data without compromising an individual’s privacy. We present methods for releasing differentially private minor allele frequencies, chi-square statistics and p-values. We compare these approaches on simulated data and on a GWAS study of canine hair length involving 685 dogs. We also propose a privacy-preserving method for finding genome-wide associations based on a differentially-private approach to penalized logistic regression.

scholarly journals Ancestral haplotype reconstruction in endogamous populations using identity-by-descent

2021 ◽  
Vol 17 (2) ◽  
pp. e1008638
Author(s):  
Kelly Finke ◽  
Michael Kourakos ◽  
Gabriela Brown ◽  
Huyen Trang Dang ◽  
Shi Jie Samuel Tan ◽  
...  
Keyword(s):  
Family Relationships ◽  
Sequence Data ◽  
Association Studies ◽  
Haplotype Diversity ◽  
Building Blocks ◽  
The United States ◽  
Genome Wide Association Studies ◽  
Ancestral Reconstruction ◽  
Identity By Descent ◽  
Endogamous Populations

In this work we develop a novel algorithm for reconstructing the genomes of ancestral individuals, given genotype or sequence data from contemporary individuals and an extended pedigree of family relationships. A pedigree with complete genomes for every individual enables the study of allele frequency dynamics and haplotype diversity across generations, including deviations from neutrality such as transmission distortion. When studying heritable diseases, ancestral haplotypes can be used to augment genome-wide association studies and track disease inheritance patterns. The building blocks of our reconstruction algorithm are segments of Identity-By-Descent (IBD) shared between two or more genotyped individuals. The method alternates between identifying a source for each IBD segment and assembling IBD segments placed within each ancestral individual. Unlike previous approaches, our method is able to accommodate complex pedigree structures with hundreds of individuals genotyped at millions of SNPs. We apply our method to an Old Order Amish pedigree from Lancaster, Pennsylvania, whose founders came to the United States from Europe during the early 18th century. The pedigree includes 1338 individuals from the past 12 generations, 394 with genotype data. The motivation for reconstruction is to understand the genetic basis of diseases segregating in the family through tracking haplotype transmission over time. Using our algorithm thread, we are able to reconstruct an average of 224 ancestral individuals per chromosome. For these ancestral individuals, on average we reconstruct 79% of their haplotypes. We also identify a region on chromosome 16 that is difficult to reconstruct—we find that this region harbors a short Amish-specific copy number variation and the gene HYDIN. thread was developed for endogamous populations, but can be applied to any extensive pedigree with the recent generations genotyped. We anticipate that this type of practical ancestral reconstruction will become more common and necessary to understand rare and complex heritable diseases in extended families.

The Non-Hodgkin Lymphomas

2017 ◽  
Author(s):  
James R. Cerhan ◽  
Claire M. Vajdic ◽  
John J. Spinelli
Keyword(s):  
Association Studies ◽  
Survival Rates ◽  
Relative Survival ◽  
The United States ◽  
Immunosuppressive Drugs ◽  
Lymphoid Tissues ◽  
Genome Wide Association Studies ◽  
Lymphoid Leukemia ◽  
Common Genetic Variants ◽  
H Pylori

The non-Hodgkin lymphomas (NHL) are a heterogeneous group of over forty lymphoid neoplasms that have undergone a major redefinition over the last twenty-five years, in part due to advances in immunology and genetics as well as implementation of the WHO classification system. NHLs are considered clonal tumors of B-cells, T-cells, or natural killer (NK) cells arrested at various stages of differentiation, regardless of whether they present in the blood (lymphoid leukemia) or lymphoid tissues (lymphoma). In the United States, the age-standardized NHL incidence rate (per 100,000) doubled from 1973 (10.2) to 2004 (21.4) and then stabilized, while five-year relative survival rates improved from 42% in 1973 to 70% in 2004. Established risk factors for NHL or specific NHL subtypes include infectious agents (HTLV-1, HIV, EBV, HHV8, HCV, H. pylori), immune dysregulation (primary immunodeficiency, transplantation, autoimmunity, and immunosuppressive drugs), family history of lymphoma, and common genetic variants identified by genome-wide association studies.

scholarly journals Genome-Wide Association Studies of Conotruncal Heart Defects with Normally Related Great Vessels in the United States

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 1030
Author(s):  
Omobola O. Oluwafemi ◽  
Fadi I. Musfee ◽  
Laura E. Mitchell ◽  
Elizabeth Goldmuntz ◽  
Hongbo M. Xie ◽  
...  
Keyword(s):  
Association Studies ◽  
Heart Defects ◽  
22Q11.2 Deletion Syndrome ◽  
The United States ◽  
Deletion Syndrome ◽  
Genome Wide Association Studies ◽  
Gene Set ◽  
Genome Wide ◽  
Gene Level ◽  
Great Vessels

Conotruncal defects with normally related great vessels (CTD-NRGVs) occur in both patients with and without 22q11.2 deletion syndrome (22q11.2DS), but it is unclear to what extent the genetically complex etiologies of these heart defects may overlap across these two groups, potentially involving variation within and/or outside of the 22q11.2 region. To explore this potential overlap, we conducted genome-wide SNP-level, gene-level, and gene set analyses using common variants, separately in each of five cohorts, including two with 22q11.2DS (N = 1472 total cases) and three without 22q11.2DS (N = 935 total cases). Results from the SNP-level analyses were combined in meta-analyses, and summary statistics from these analyses were also used in gene and gene set analyses. Across all these analyses, no association was significant after correction for multiple comparisons. However, several SNPs, genes, and gene sets with suggestive evidence of association were identified. For common inherited variants, we did not identify strong evidence for shared genomic mechanisms for CTD-NRGVs across individuals with and without 22q11.2 deletions. Nevertheless, several of our top gene-level and gene set results have been linked to cardiogenesis and may represent candidates for future work.

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