scholarly journals ddRAD sequencing-based identification of inter-genepool SNPs and association analysis in Brassica juncea

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Jebi Sudan ◽  
Ravinder Singh ◽  
Susheel Sharma ◽  
Romesh K. Salgotra ◽  
Varun Sharma ◽  
...  
Keyword(s):  
Brassica Juncea ◽  
Association Analysis ◽  
Sequence Data ◽  
Read Depth ◽  
Nucleotide Polymorphisms ◽  
Variable Regions ◽  
Mean Values ◽  
Six Traits ◽  
A Genome ◽  
Significant Difference

Abstract Background Narrow genetic base, complex allo-tetraploid genome and presence of repetitive elements have led the discovery of single nucleotide polymorphisms (SNPs) in Brassica juncea (AABB; 2n = 4x = 36) at a slower pace. Double digest RAD (ddRAD) - a genome complexity reduction technique followed by NGS was used to generate a total of 23 million paired-end reads from three genotypes each of Indian (Pusa Tarak, RSPR-01 and Urvashi) and Exotic (Donskaja IV, Zem 1 and EC287711) genepools. Results Sequence data analysis led to the identification of 10,399 SNPs in six genotypes at a read depth of 10x coverage among the genotypes of two genepools. A total of 44 hyper-variable regions (nucleotide variation hotspots) were also found in the genome, of which 93% were found to be a part of coding genes/regions. The functionality of the identified SNPs was estimated by genotyping a subset of SNPs on MassARRAY® platform among a diverse set of B. juncea genotypes. SNP genotyping-based genetic diversity and population studies placed the genotypes into two distinct clusters based mostly on the place of origin. The genotypes were also characterized for six morphological traits, analysis of which revealed a significant difference in the mean values between Indian and Exotic genepools for six traits. The association analysis for six traits identified a total of 45 significant marker-trait associations on 11 chromosomes of A- and B- group of progenitor genomes. Conclusions Despite narrow diversity, the ddRAD sequencing was able to identify large number of nucleotide polymorphisms between the two genepools. Association analysis led to the identification of common SNPs/genomic regions associated between flowering and maturity traits, thereby underscoring the possible role of common chromosomal regions-harboring genes controlling flowering and maturity in Brassica juncea.

scholarly journals The ABO blood group locus and a chromosome 3 gene cluster associate with SARS-CoV-2 respiratory failure in an Italian-Spanish genome-wide association analysis

2020 ◽  
Author(s):  
David Ellinghaus ◽  
Frauke Degenhardt ◽  
Luis Bujanda ◽  
Maria Buti ◽  
Agustín Albillos ◽  
...  
Keyword(s):  
Respiratory Failure ◽  
Blood Group ◽  
Association Analysis ◽  
Meta Analysis ◽  
Genome Wide Association ◽  
Nucleotide Polymorphisms ◽  
Genome Wide Association Analysis ◽  
Genome Wide ◽  
A Genome ◽  
Group Locus

ABSTRACTBackgroundRespiratory failure is a key feature of severe Covid-19 and a critical driver of mortality, but for reasons poorly defined affects less than 10% of SARS-CoV-2 infected patients.MethodsWe included 1,980 patients with Covid-19 respiratory failure at seven centers in the Italian and Spanish epicenters of the SARS-CoV-2 pandemic in Europe (Milan, Monza, Madrid, San Sebastian and Barcelona) for a genome-wide association analysis. After quality control and exclusion of population outliers, 835 patients and 1,255 population-derived controls from Italy, and 775 patients and 950 controls from Spain were included in the final analysis. In total we analyzed 8,582,968 single-nucleotide polymorphisms (SNPs) and conducted a meta-analysis of both case-control panels.ResultsWe detected cross-replicating associations with rs11385942 at chromosome 3p21.31 and rs657152 at 9q34, which were genome-wide significant (P<5×10−8) in the meta-analysis of both study panels, odds ratio [OR], 1.77; 95% confidence interval [CI], 1.48 to 2.11; P=1.14×10−10 and OR 1.32 (95% CI, 1.20 to 1.47; P=4.95×10−8), respectively. Among six genes at 3p21.31, SLC6A20 encodes a known interaction partner with angiotensin converting enzyme 2 (ACE2). The association signal at 9q34 was located at the ABO blood group locus and a blood-group-specific analysis showed higher risk for A-positive individuals (OR=1.45, 95% CI, 1.20 to 1.75, P=1.48×10−4) and a protective effect for blood group O (OR=0.65, 95% CI, 0.53 to 0.79, P=1.06×10−5).ConclusionsWe herein report the first robust genetic susceptibility loci for the development of respiratory failure in Covid-19. Identified variants may help guide targeted exploration of severe Covid-19 pathophysiology.

scholarly journals Genome-wide analysis of thyroid function in Australian adolescents highlights SERPINA7 and NCOA3

2021 ◽  
Author(s):  
James Nolan ◽  
Purdey J Campbell ◽  
Suzanne J Brown ◽  
Gu Zhu ◽  
Scott Gordon ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Thyroid Function ◽  
Association Analysis ◽  
Genetic Factors ◽  
Meta Analysis ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genome Wide Analysis ◽  
Genome Wide ◽  
A Genome

Objective Genetic factors underpin the narrow intraindividual variability of thyroid function, although precise contributions of environmental versus genetic factors remain uncertain. We sought to clarify the heritability of thyroid function traits and thyroid peroxidase antibody (TPOAb) positivity and identify single nucleotide polymorphisms (SNPs) contributing to the trait variance. Methods Heritability of thyroid stimulating hormone (TSH), free T4 (fT4), free T3 (fT3) and TPOAb in a cohort of 2854 euthyroid, dizygous and monozygous twins (age range 11.9-16.9 years) from the Brisbane Longitudinal Twin Study (BLTS) was assessed using structural equation modelling. A genome-wide analysis was conducted on 2832 of these individuals across 7,522,526 single nucleotide polymorphisms as well as gene-based association analyses. Replication analysis of the association results was performed in the Raine Study (n= 1115) followed by meta-analysis to maximise power for discovery. Results Heritability of thyroid function parameters in the BLTS was 70.8% (95% CI: 66.7-74.9%) for TSH, 67.5% (59.8-75.3%) for fT4, 59.7% (54.4-65.0%) for fT3 and 48.8% (40.6-56.9%) for TPOAb. The genome-wide association study (GWAS) in the discovery cohort identified a novel association between rs2026401 upstream of NCOA3 and TPOAb. GWAS meta-analysis found associations between TPOAb and rs445219, also near NCOA3, and fT3 and rs12687280 near SERPINA7. Gene-based association analysis highlighted SERPINA7 for fT3 and NPAS3 for fT4. Conclusion Our findings resolve former contention regarding heritability estimates of thyroid function traits and TPOAb positivity. GWAS and gene-based association analysis identified variants accounting for a component of this heritability.

Autosome-wide Copy Number Variation Association Analysis for Rheumatoid Arthritis Using the WTCCC High-density SNP Genotype Data

2011 ◽  
Vol 38 (5) ◽  
pp. 797-801 ◽  
Author(s):  
MOHAMMED UDDIN ◽  
MITCH STURGE ◽  
PROTON RAHMAN ◽  
MICHAEL O. WOODS
Keyword(s):  
Rheumatoid Arthritis ◽  
Association Analysis ◽  
Lupus Erythematosus ◽  
Copy Number ◽  
Association Studies ◽  
Copy Number Variations ◽  
Transcription Activator ◽  
Variable Regions ◽  
Genome Wide ◽  
A Genome

Objective.Rheumatoid arthritis (RA) is a complex autoimmune rheumatic disease that is strongly influenced by genetic factors. Numerous genes are convincingly associated with RA, including genes in tumor necrosis factor signaling (TNF) and the nuclear factor-κB pathway. To date, except for genes within the HLA region, no data exist regarding potential copy number variations (CNV) involving RA-associated genes. We set out to identify genes affected by CNV that are associated with RA at a genome-wide level.Methods.Data from the Wellcome Trust Case Control Consortium (WTCCC) were used in our analyses. The initial WTCCC cohort genotyped 3004 controls and 1999 RA cases using the GeneChip 500k Mapping Array Set. We performed a comparative intensity analysis using the PennCNV algorithm, which uses a hidden Markov model to detect CNV. A total of 2271 controls and 1572 RA samples passed quality control criteria and were included for association analysis. Association analysis was performed in 2 phases: (1) to identify CNV that are < 1 Mb with a population frequency < 5%; and (2) to identify large CNV that are > 1 Mb. Fishers’ exact test was performed to quantify significance of the CNV.Results.We observed that the genome-wide CNV burden is 2-fold higher in patients with RA compared with controls. We identified 11 rare copy number variable regions with < 5% frequency that had an association with RA that reached a p < 1 × 10−4. These include TNFAIP3 and TNIP1, which has been implicated in association studies for RA, systemic lupus erythematosus, and psoriasis. We identified CNV involving IRF1, which functions as a transcription activator of genes induced by interferons; ALOX5AP and LCP2, involved in inflammatory mediation; B2M, an MHC-class I associated gene; and PRKCH, a gene involved in T cell signaling pathways. A 57 kb deletion with 1% frequency in RA cases at 7p21.3 was also observed. Six of these loci overlap with CNV catalogued in the Database of Genomic Variants.Conclusion.This is the first study to identify non-HLA RA-associated CNV using genome-wide analyses. Validation and functional significance of these deletions/duplications in RA and other autoimmune diseases need to be further investigated.

scholarly journals Genome-wide association analysis reveals QTL and candidate mutations involved in white spotting in cattle

2019 ◽  
Vol 51 (1) ◽  
Author(s):  
Swati Jivanji ◽  
Gemma Worth ◽  
Thomas J. Lopdell ◽  
Anna Yeates ◽  
Christine Couldrey ◽  
...  
Keyword(s):  
Association Analysis ◽  
Molecular Mechanisms ◽  
Coat Color ◽  
Sequence Data ◽  
Genome Wide Association ◽  
Whole Genome Sequence ◽  
Genome Wide Association Analysis ◽  
Genome Wide ◽  
Holstein Friesian ◽  
A Genome

Abstract Background White spotting of the coat is a characteristic trait of various domestic species including cattle and other mammals. It is a hallmark of Holstein–Friesian cattle, and several previous studies have detected genetic loci with major effects for white spotting in animals with Holstein–Friesian ancestry. Here, our aim was to better understand the underlying genetic and molecular mechanisms of white spotting, by conducting the largest mapping study for this trait in cattle, to date. Results Using imputed whole-genome sequence data, we conducted a genome-wide association analysis in 2973 mixed-breed cows and bulls. Highly significant quantitative trait loci (QTL) were found on chromosomes 6 and 22, highlighting the well-established coat color genes KIT and MITF as likely responsible for these effects. These results are in broad agreement with previous studies, although we also report a third significant QTL on chromosome 2 that appears to be novel. This signal maps immediately adjacent to the PAX3 gene, which encodes a known transcription factor that controls MITF expression and is the causal locus for white spotting in horses. More detailed examination of these loci revealed a candidate causal mutation in PAX3 (p.Thr424Met), and another candidate mutation (rs209784468) within a conserved element in intron 2 of MITF transcripts expressed in the skin. These analyses also revealed a mechanistic ambiguity at the chromosome 6 locus, where highly dispersed association signals suggested multiple or multiallelic QTL involving KIT and/or other genes in this region. Conclusions Our findings extend those of previous studies that reported KIT as a likely causal gene for white spotting, and report novel associations between candidate causal mutations in both the MITF and PAX3 genes. The sizes of the effects of these QTL are substantial, and could be used to select animals with darker, or conversely whiter, coats depending on the desired characteristics.

Investigating the likely association between genetic ancestry and COVID-19 manifestation (Preprint)

2020 ◽  
Author(s):  
Ranajit Das ◽  
Sudeep D Ghate
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Genome Wide Association Study ◽  
Genomic Sequence ◽  
Sequence Data ◽  
Antiviral Response ◽  
Genetic Ancestry ◽  
Recovery Ratio ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
A Genome

UNSTRUCTURED The novel coronavirus 2019-nCoV/SARS-CoV-2 infection has shown discernible variability across the globe. While in some countries people are recovering relatively quicker, in others, recovery times have been comparatively longer and numbers of those succumbing to it high. In this study, we aimed to evaluate the likely association between an individual’s ancestry and the extent of COVID-19 manifestation employing Europeans as the case study. We employed 10,215 ancient and modern genomes across the globe assessing 597,573 single nucleotide polymorphisms (SNPs). Pearson’s correlation coefficient (r) between various ancestry proportions of European genomes and COVID-19 death/recovery ratio was calculated and its significance was statistically evaluated. We found significant positive correlation (p=0.03) between European Mesolithic hunter gatherers (WHG) ancestral fractions and COVID-19 death/recovery ratio and a marginally significant negative correlation (p=0.06) between Neolithic Iranian ancestry fractions and COVID-19 death/recovery ratio. We further identified 404 immune response related single nucleotide polymorphisms (SNPs) by comparing publicly available 753 genomes from various European countries against 838 genomes from various Eastern Asian countries in a genome wide association study (GWAS). Prominently, we identified that SNPs associated with Interferon stimulated antiviral response, Interferon-stimulated gene 15 mediated antiviral mechanism and 2′-5′ oligoadenylate synthase mediated antiviral response show large differences in allele frequencies between Europeans and East Asians. Overall, to the best of our knowledge, this is the first study evaluating the likely association between genetic ancestry and COVID-19 manifestation. While our current findings improve our overall understanding of the COVID-19, we note that the development of effective therapeutics will benefit immensely from more detailed analyses of individual genomic sequence data from COVID-19 patients of varied ancestries.

Serum Folate Measurement by Chemiluminescence in Patients with Paraproteinaemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4193-4193
Author(s):  
Lisa J Wakeman ◽  
John O Lewis ◽  
Keith Morris ◽  
Ann Benton ◽  
Roger C Munro ◽  
...  
Keyword(s):  
T Test ◽  
Serum Folate ◽  
Albumin Concentration ◽  
Reference Ranges ◽  
Variable Regions ◽  
Mean Values ◽  
Significant Difference ◽  
The Mean ◽  
Normal Controls ◽  
Paired T Test

Abstract Introduction: Paraproteins cause interference in many assays systems due to increased viscosity and/or by non-specific binding to either analytes or reagents which may variably affect the results. There is abundant evidence to indicate that performance characteristics of automated, competitive protein-binding assays for folate assays are normally sound, but there is a paucity of data comparing folate assays in patients with paraproteinaemia compared to normals. Method: Serum samples were prepared from venous blood taken into Greiner Vacuette containers (code: 456018) in fifty patients with paraproteinaemia (IgG Kappa, n = 20: IgG Lambda, n = 9: IgM Kappa, n = 6: IgM Lambda, n = 4: IgA Kappa, n = 5: IgA Lambda, n = 3: multiclonal, n = 3). Serum folate assays were measured according to manufacturer’s instructions on Beckman-Coulter Access and Abbott Architect haematinics analysers on the day of sample collection. Results: The ratio of means of serum protein concentrations in the paraprotein sub-groups compared to the mean values of age/gender related reference ranges were: IgG = 1.57: IgM = 7.8: IgA = 6.3. Serum albumin concentration was normal in all patients. Mean serum folate results (±1SD) for paraprotein patients and normals controls (laboratory personnel) are shown in the table below: Serum Folate (μg/L) Access Architect paired t-test Normal controls (n = 50) 5.98 (±3.57) 5.01 (±3.14) p&lt;0.05 Paraprotein patients (n = 50) 5.08 (±2.79) 5.01 (±3.03) p0.700 When analysed using the paired-t-test serum folate was significantly different in normal subjects using the Access compared to the Architect. However, no such significant difference between the two systems was observed in the paraproteinaemia group. Although the mean serum folate in normals was higher compared to the paraprotein group as analysed by the Access, this difference was not significant when analysed using the two-sample t-test. Interestingly the mean serum folate when analysed in the two groups using the Architect gave identical mean values. There were no statistically significant differences between the two methods in any of the paraprotein sub-types (p&gt;0.05 in each case). Conclusions: The complex and variable mixture of proteins present in paraproteinaemias pose potential erroneous measurement in immunoassay systems. This is because they may interfere with the associated antigen-antibody reactions which are dependant on complimentary matching shapes being assumed by the antibody variable regions of the immunoglobulin. Despite this, our data using two distinct chemiluminescence analysers for folate measurement indicate no statistically significant difference for this parameter between patients with paraproteinaemia compared to normal controls. However, it has yet to be determined whether differing results between these two groups are generated using different analytical techniques.

scholarly journals A Missense Mutation in the MYBPH Gene Is Associated With Abdominal Fat Traits in Meat-Type Chickens

2021 ◽  
Vol 12 ◽  
Author(s):  
Priscila Anchieta Trevisoli ◽  
Gabriel Costa Monteiro Moreira ◽  
Clarissa Boschiero ◽  
Aline Silva Mello Cesar ◽  
Juliana Petrini ◽  
...  
Keyword(s):  
Protein Function ◽  
Sequence Data ◽  
Carcass Traits ◽  
Additive Model ◽  
Abdominal Fat ◽  
Whole Genome Sequence ◽  
P Value ◽  
Nucleotide Polymorphisms ◽  
A Genome ◽  
Meat Type

Chicken is an important source of protein for human nutrition and a model system for growth and developmental biology. Although the genetic architecture of quantitative traits in meat-type chickens has been the subject of ongoing investigation, the identification of mutations associated with carcass traits of economic interest remains challenging. Therefore, our aim was to identify predicted deleterious mutation, which potentially affects protein function, and test if they were associated with carcass traits in chickens. For that, we performed a genome-wide association analysis (GWAS) for breast, thigh and drumstick traits in meat-type chickens and detected 19 unique quantitative trait loci (QTL). We then used: (1) the identified windows; (2) QTL for abdominal fat detected in a previous study with the same population and (3) previously obtained whole genome sequence data, to identify 18 predicted deleterious single nucleotide polymorphisms (SNPs) in those QTL for further association with breast, thigh, drumstick and abdominal fat traits. Using the additive model, a predicted deleterious SNP c.482C &gt; T (SIFT score of 0.4) was associated (p-value &lt; 0.05) with abdominal fat weight and percentage. This SNP is in the second exon of the MYBPH gene, and its allele frequency deviates from Hardy–Weinberg equilibrium. In conclusion, our study provides evidence that the c.482C &gt; T SNP in the MYBPH gene is a putative causal mutation for fat deposition in meat-type chickens.

scholarly journals Investigatingthe likely association between genetic ancestry and COVID-19 manifestation

2020 ◽  
Author(s):  
Ranajit Das ◽  
Sudeep D. Ghate
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Genome Wide Association Study ◽  
Genomic Sequence ◽  
Sequence Data ◽  
Antiviral Response ◽  
Genetic Ancestry ◽  
Recovery Ratio ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
A Genome

AbstractThe novel coronavirus 2019-nCoV/SARS-CoV-2 infection has shown discernible variability across the globe. While in some countries people are recovering relatively quicker, in others, recovery times have been comparatively longer and numbers of those succumbing to it high. In this study, we aimed to evaluate the likely association between an individual’s ancestry and the extent of COVID-19 manifestation employing Europeans as the case study. We employed 10,215 ancient and modern genomes across the globe assessing 597,573 single nucleotide polymorphisms (SNPs). Pearson’s correlation coefficient (r) between various ancestry proportions of European genomes and COVID-19 death/recovery ratio was calculated and its significance was statistically evaluated. We found significant positive correlation (p=0.03) between European Mesolithic hunter gatherers (WHG) ancestral fractions and COVID-19 death/recovery ratio and a marginally significant negative correlation (p=0.06) between Neolithic Iranian ancestry fractions and COVID-19 death/recovery ratio. We further identified 404 immune response related single nucleotide polymorphisms (SNPs) by comparing publicly available 753 genomes from various European countries against 838 genomes from various Eastern Asian countries in a genome wide association study (GWAS). Prominently, we identified that SNPs associated with Interferon stimulated antiviral response, Interferon-stimulated gene 15 mediated antiviral mechanism and 2′-5′ oligoadenylate synthase mediated antiviral response show large differences in allele frequencies between Europeans and East Asians. Overall, to the best of our knowledge, this is the first study evaluating the likely association between genetic ancestry and COVID-19 manifestation. While our current findings improve our overall understanding of the COVID-19, we note that the development of effective therapeutics will benefit immensely from more detailed analyses of individual genomic sequence data from COVID-19 patients of varied ancestries.

A COMPARISON OF TWO METHODS FOR MEASUREMENT OF ALDOSTERONE SECRETION RATE IN MAN

1966 ◽  
Vol 53 (2) ◽  
pp. 177-188 ◽  
Author(s):  
P. Lund-Johansen ◽  
T. Thorsen ◽  
K. F. Støa
Keyword(s):  
Urinary Excretion ◽  
Normal Subjects ◽  
Secretion Rate ◽  
Aldosterone Secretion ◽  
Simple Method ◽  
Mean Values ◽  
Pathological Conditions ◽  
Significant Difference ◽  
Derivative Method ◽  
The Mean

ABSTRACT A comparison has been made between (A), a relatively simple method for the measurement of aldosterone secretion rate, based on paper chromatography and direct densitometry of the aldosterone spot and (B) a more elaborate isotope derivative method. The mean secretion rate in 9 normal subjects was 112 ± 26 μg per 24 hours (method A) and 135 ± 35 μg per 24 hours (method B). The »secretion rate« in one adrenalectomized subject after the intravenous injection of 250 μg of aldosterone was 230 μg per 24 hours (method A) and 294 μg per 24 hours (method B). There was no significant difference in the mean values, and correlation between the two methods was good (r = 0.80). It is concluded that the densitometric method is suitable for clinical purposes as well as research, being more rapid and less expensive than the isotope derivative method. Method A also measures the urinary excretion of the aldosterone 3-oxo-conjugate, which is of interest in many pathological conditions. The densitometric method is obviously the less sensitive and a prerequisite for its use is an aldosterone secretion of 20—30 μg per 24 hours. Lower values are, however, rare in adults.

Effectiveness of Brushing Associated with Oral Irrigation in Maintenance of Peri-Implant Tissues and Overdentures: Clinical Parameters and Patient Satisfaction.

2020 ◽  
Author(s):  
Marcela Moreira Salles ◽  
Viviane de Cássia Oliveira ◽  
Ana Paula Macedo ◽  
Claudia Helena Silva-Lovato ◽  
Helena de Freitas Oliveira Paranhos
Keyword(s):  
Patient Satisfaction ◽  
Analogue Scale ◽  
Ring System ◽  
Complete Dentures ◽  
Gingival Index ◽  
Prosthetic Rehabilitation ◽  
Mean Values ◽  
Probing Depth ◽  
Significant Difference ◽  
High Level

Implant-supported prostheses hygiene and peri-implant tissues health are considered to be predictive factors for successful prosthetic rehabilitation. Therefore, the purpose of this study was to evaluate the effectiveness of brushing associated with oral irrigation measured as biofilm-removing capacity, maintenance of healthy oral tissues, and patient satisfaction. A randomized, crossover clinical trial was conducted with 38 patients who wore conventional maxillary complete dentures and mandibular overdentures retained by the O-ring system. The patients were instructed to use the following hygiene methods for 14 days: mechanical brushing [MB (brush and dentifrice - Control)]; and MB with oral irrigation [WP (Waterpik - Experimental)]. Biofilm-removing capacity and maintenance of healthy oral tissues were evaluated by the Modified Plaque Index (PI), Gingival Index (GI), Probing Depth (PD), and Bleeding on Probing Index (BP) recorded at baseline and after each method. In parallel, patients answered a specific questionnaire using a Visual Analogue Scale after each hygiene method. Data were analyzed by Friedman and Wilcoxon tests (α=0.05). The results showed significantly lower PI, GI, PD, and BP indices after application of the hygiene methods (P&lt;0.001) than those observed at baseline. However, no significant difference was found between MB and WP. The satisfaction questionnaire responses to both methods showed high mean values for all questions, with no statistically significant difference found between the answers given after the use of MB and WP (P&gt;0.05). The findings suggest that WP was effective in reducing PI, GI, PD, and BP indices and provided a high level of patient satisfaction.

Sign in / Sign up

Export Citation Format

Share Document