EZTraits: a Programmable Tool to Evaluate Multi-site Deterministic Traits

The vast majority of human traits, including many disease phenotypes, are affected by alleles at numerous genomic loci. With a continually increasing set of variants with published clinical disease or biomarker associations, an easy-to-use tool for non-programmers to rapidly screen VCF files for risk alleles is needed. We have developed EZTraits as a tool to quickly evaluate genotype data (e.g. from microarrays), against a set of rules defined by the user. These rules can be defined directly in the scripting language Lua , for genotype calls using variant ID (RS number) or chromosomal position. Alternatively, EZTraits can parse simple and intuitive text including concepts like ' any ' or ' all '. Thus, EZTraits is designed to support rapid genetic analysis and hypothesis-testing by researchers, regardless of programming experience or technical background.

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PSVII-27 Genetic analysis of disease resilience of nursery-to-finish pigs under a natural disease challenge model using reaction norms

Journal of Animal Science ◽

10.1093/jas/skab235.429 ◽

2021 ◽

Vol 99 (Supplement_3) ◽

pp. 235-235

Author(s):

Jian Cheng ◽

KyuSang Lim ◽

Austin Putz ◽

Anna Wolc ◽

John Harding ◽

...

Keyword(s):

Genetic Model ◽

Average Daily Gain ◽

Genetic Correlations ◽

Reaction Norm ◽

Cubic Spline ◽

Clinical Disease ◽

Random Regression ◽

Disease Phenotypes ◽

Linear Reaction ◽

Better Than

Abstract Disease resilience is the ability of an animal to maintain performance across environments with different disease challenge loads (CL) and can be quantified using random regression reaction norm models that describe phenotype as a function of CL. Objectives of this study were to: 1) develop measures of CL using growth rate and clinical disease phenotypes under a natural disease challenge; 2) evaluate genetic variation in disease resilience. Data used were late nursery and finisher growth rates and clinical disease phenotypes, including medical treatment and mortality rates, and subjective health scores, collected on 50 batches of 60/75 crossbred (LRxY) barrows under a polymicrobial natural disease challenge. All pigs were genotyped using a 650K SNP panel. Different CL were derived from estimates of contemporary group effects and used as environmental covariates in reaction norm analyses of average daily gain (ADG) and treatment rate (TRT). The CL were compared based on model loglikelihoods and estimates of genetic variance, using both linear and cubic spline reaction norm models. Linear reaction norm models fitted the data significantly better than the standard genetic model and the cubic spline models fitted the data significantly better than the linear reaction norm model for most traits. CL based on early finisher ADG provided the best fit for nursery ADG, while CL based on clinical disease phenotypes was best for finisher ADG and TRT. With increasing CL, estimates of heritability for ADG initially decreased and then increased, while estimates of heritability for TRT generally increased with CL. Genetic correlations were low between ADG or TRT at high versus low CL but high for close CLs. Results can be used to select more resilient pigs across different CL levels, or high-performance animals at a given CL level, or a combination of these. Funded by Genome Canada, Genome Alberta, USDA-NIFA, and PigGenCanada.

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Streptococci and enterococci

Oxford Textbook of Medicine ◽

10.1093/med/9780198746690.003.0106 ◽

2020 ◽

pp. 965-975

Author(s):

Dennis L. Stevens ◽

Sarah Hobdey

Keyword(s):

Cell Wall ◽

Genetic Analysis ◽

Clinical Relevance ◽

Domestic Animals ◽

Clinical Disease ◽

Haemolytic Activity ◽

Diverse Group ◽

Oral Streptococci ◽

Infected Wounds ◽

Cell Wall Carbohydrates

The term streptococcus was first used by Billroth in 1874 to describe chain-forming cocci found in infected wounds. The streptococci are a diverse group of Gram-positive pathogenic cocci that cause clinical disease in humans and domestic animals. They are traditionally classified on the basis of serological reactions, particularly Lancefield grouping based on cell-wall carbohydrates, and haemolytic activity on blood agar. Six groups can be defined by genetic analysis: pyogenic streptococci, milleri or anginosus group, mitis group, salivarius group, mutans group, and bovis group. Since the medically important members of the mitis, salivarius, and mutans groups are all oral streptococci and are of clinical relevance predominantly in endocarditis, they will be considered together in this chapter.

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Comments on Local cod (Gadus morhua) revealed by egg surveys and population genetic analysis after longstanding depletion on the Swedish Skagerrak Coast by Svedäng et al.

ICES Journal of Marine Science ◽

10.1093/icesjms/fsz095 ◽

2019 ◽

Vol 76 (4) ◽

pp. 1209-1211 ◽

Cited By ~ 1

Author(s):

Massimiliano Cardinale ◽

Stefano Mariani ◽

Joakim Hjelm

Keyword(s):

Genetic Analysis ◽

Population Genetic ◽

Gadus Morhua ◽

Genetic Data ◽

Scientific Basis ◽

Coastal Ecosystems ◽

Genotype Data ◽

Demographic Expansion ◽

Population Genetic Analysis ◽

Relict Population

Abstract Svedäng et al. (2018) concluded that “the occurrence of locally spawned cod eggs suggests that spawning on the Swedish Skagerrak coast takes place, which belong to either a coastal subpopulation that is a remnant stock of a once much larger cod population, or a newly formed subpopulation that is now successfully inhabiting the coastal ecosystems along the Swedish Skagerrak coast”. However, after carefully reviewing the results and the data presented by the authors, we were no longer convinced that the information presented provided enough evidence for a local, distinct, coastal cod population in the Swedish Skagerrak. Thus, we requested the original genotype data, which the authors kindly provided to us. This allowed us to explore the substructure of these samples further using STRUCTURE 2.3.2. Re-analysis of the data consistently rejects the existence of an independent coastal Swedish stock in contrast with Svedäng et al. (2018) conclusions. We acknowledge the observation of cod spawning in the area but, based on re-analysis of the original genetic data of Svedäng et al. (2018), we currently lack the scientific basis to assume the existence of established local stocks, and even less the demographic expansion of an older, relict population in the area.

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Apolipoprotein E Polymorphism and Clinical Disease Phenotypes in Arab Patients with Schizophrenia

Neuropsychobiology ◽

10.1159/000236446 ◽

2009 ◽

Vol 60 (2) ◽

pp. 67-72 ◽

Cited By ~ 9

Author(s):

A.O. Akanji ◽

J.U. Ohaeri ◽

S.N. Al-Shammri ◽

H.R. Fatania

Keyword(s):

Apolipoprotein E ◽

Clinical Disease ◽

Disease Phenotypes ◽

Apolipoprotein E Polymorphism

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Association Study of the Dystrobrevin-Binding Gene With Schizophrenia in Australian and Indian Samples

Twin Research and Human Genetics ◽

10.1375/twin.9.4.531 ◽

2006 ◽

Vol 9 (4) ◽

pp. 531-539 ◽

Cited By ~ 17

Author(s):

Elizabeth G. Holliday ◽

Herlina Y. Handoko ◽

Michael R. James ◽

John J. McGrath ◽

Deborah A. Nertney ◽

...

Keyword(s):

Risk Allele ◽

Risk Marker ◽

Genotype Data ◽

Nucleotide Polymorphisms ◽

Hapmap Phase ◽

Single Nucleotide ◽

Risk Alleles ◽

Sufficient Power ◽

Allele Effect ◽

Multiple Samples

AbstractNumerous studies have reported association between variants in the dystrobrevin binding protein 1 (dysbindin) gene (DTNBP1) and schizophrenia. However, the pattern of results is complex and to date, no specific risk marker or haplotype has been consistently identified. The number of single nucleotide polymorphisms (SNPs) tested in these studies has ranged from 5 to 20. We attempted to replicate previous findings by testing 16 SNPs in samples of 41 Australian pedigrees, 194 Australian cases and 180 controls, and 197 Indian pedigrees. No globally significant evidence for association was observed in any sample, despite power calculations indicating sufficient power to replicate several previous findings. Possible explanations for our results include sample differences in background linkage dis-equilibrium and/or risk allele effect size, the presence of multiple risk alleles upon different haplotypes, or the presence of a single risk allele upon multiple haplotypes. Some previous associations may also represent false positives. Examination of Caucasian HapMap phase II genotype data spanning theDTNBP1region indicates upwards of 40 SNPs are required to satisfactorily assess all nonredundant variation withinDTNBP1and its potential regulatory regions for association with schizophrenia. More comprehensive studies in multiple samples will be required to determine whether specificDTNBP1variants function as risk factors for schizophrenia.

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Streptococci and enterococci

Oxford Textbook of Medicine ◽

10.1093/med/9780199204854.003.070602_update_001 ◽

2010 ◽

pp. 670-679

Author(s):

Dennis L. Stevens

Keyword(s):

Cell Wall ◽

Genetic Analysis ◽

Domestic Animals ◽

Clinical Disease ◽

Blood Agar ◽

Haemolytic Activity ◽

Diverse Group ◽

Gram Positive ◽

Cell Wall Carbohydrates

The streptococci are a diverse group of Gram-positive pathogenic cocci that cause clinical disease in humans and domestic animals. They are traditionally classified on the basis of serological reactions, particularly Lancefield grouping based on cell-wall carbohydrates, and haemolytic activity on blood agar. Six groups can be defined by genetic analysis: pyogenic streptococci, milleri or anginosus group, mitis group, salivarius group, mutans group, and bovis group....

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Genetic analysis of Japanese primary open-angle glaucoma patients and clinical characterization of risk alleles near CDKN2B-AS1, SIX6 and GAS7

PLoS ONE ◽

10.1371/journal.pone.0186678 ◽

2017 ◽

Vol 12 (12) ◽

pp. e0186678 ◽

Cited By ~ 12

Author(s):

Yukihiro Shiga ◽

Koji M. Nishiguchi ◽

Yosuke Kawai ◽

Kaname Kojima ◽

Kota Sato ◽

...

Keyword(s):

Genetic Analysis ◽

Primary Open Angle Glaucoma ◽

Open Angle Glaucoma ◽

Open Angle ◽

Risk Alleles

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P825 The impact of a SNP-dose–response effect on course of inflammatory bowel disease: a numerical analysis of SNP distribution within the Swiss IBD Cohort Study

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.953 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S640-S641

Author(s):

L Biedermann ◽

L Denoth ◽

J B Rossel ◽

M Butter ◽

S Vavricka ◽

...

Keyword(s):

Cohort Study ◽

Risk Score ◽

Association Studies ◽

Large Population ◽

Median Number ◽

Clinical Disease ◽

Genome Wide Association Studies ◽

Risk Alleles ◽

Individual Snps ◽

The Impact

Abstract Background Several large genome wide association studies have identified an increasing number of IBD risk loci with currently more than 240 established loci and generated robust data on disease association. However, knowledge remains limited on distinctive associations to specific clinical characteristics. The Swiss IBD Cohort Study (SIBDCS) represents a large prospective cohort study with clinically and phenotypically sound data collection since 2006 including genotyping. In this study, we aimed to determine individual associations of known risk loci with clinical features of patients in the SIBDCS, as well as their combined effect on clinical outcomes. Methods Based on 158 analysed SNPs, we investigated the numerical distribution of risk alleles and determined an individual SNP risk score (defined as percentage of risk alleles; i.e. number of risk alleles divided by twice the number of given SNPs multiplied with 100). We then performed linear regression modelling to investigate, whether relevant clinical disease characteristics associate with this SNP risk score. Further, for each given clinical outcome, a model was run with all SNPs as potential predictors, and the number of significant associations per SNP counted. Results In a total of 2304 genotyped patients, we observed a median number of risk alleles of 167, 168 and 167 for IBD overall, CD and UC/IC, respectively with a narrow inter quartile range [11 (q25 = 162, q75 = 173) for IBD and CD; 12 (q25 = 161, q75 = 173) for UC/IC]. A higher SNP risk score was significantly associated with any complications (defined as a composite of any or more of colorectal cancer, colon dysplasia, intestinal lymphoma, osteopenia/-porosis, anaemia, deep venous thrombosis, pulmonary embolism, nephro- or cholelithiasis, malabsorption syndrome, massive haemorrhage, perforation/peritonitis, pouchitis), stenosis in CD patients; pancolitis, conversion to CD, female sex in UC patients; higher clinical disease activity in both CD & UC. Regarding individual SNPs, we identified substantial differences in terms of the frequency of associations to disease-related outcomes with up to 11 for rs4899554 in CD and 7 for rs9557195 in UC, respectively. Conclusion In our large population of IBD patients there is high per patient frequency of hetero- and homozygous SNP risk alleles. The association of higher SNP risk score with several disease-related outcomes indicates a potential interplay of per patient given SNP risk alleles.

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