scholarly journals Population Differentiation at the HLA Genes

2017 ◽  
Author(s):  
Débora Y. C. Brandt ◽  
Jônatas César ◽  
Jérôme Goudet ◽  
Diogo Meyer
Keyword(s):  
Population Differentiation ◽  
Balancing Selection ◽  
Global Scale ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Hla Genes ◽  
Genome Wide ◽  
Different Populations ◽  
Genomic Regions

ABSTRACTBalancing selection is defined as a class of selective regimes that maintain polymorphism above what is expected under neutrality. Theory predicts that balancing selection reduces population differentiation, as measured by FST. However, balancing selection regimes in which different sets of alleles are maintained in different populations could increase population differentiation. To tackle this issue, we investigated population differentiation at the HLA genes, which constitute the most striking example of balancing selection in humans. We found that population differentiation of single nucleotide polymorphisms (SNPs) at the HLA genes is on average lower than that of SNPs in other genomic regions. However, this result depends on accounting for the differences in allele frequency between selected and putatively neutral sites. Our finding of reduced differentiation at SNPs within HLA genes suggests a predominant role of shared selective pressures among populations at a global scale. However, in pairs of closely related populations, where genome-wide differentiation is low, differentiation at HLA is higher than in other genomic regions. This pattern was reproduced in simulations of overdominant selection. We conclude that population differentiation at the HLA genes is generally lower than genome-wide, but it may be higher for recently diverged population pairs, and that this pattern can be explained by a simple overdominance regime.

scholarly journals Type 2 Diabetes (T2D) Associated Polymorphisms Regulate Expression of Adjacent Transcripts in Transformed Lymphocytes, Adipose, and Muscle from Caucasian and African-American Subjects

2011 ◽  
Vol 96 (2) ◽  
pp. E394-E403 ◽  
Author(s):  
Neeraj K. Sharma ◽  
Kurt A. Langberg ◽  
Ashis K. Mondal ◽  
Steven C. Elbein ◽  
Swapan K. Das
Keyword(s):  
Genome Wide Association ◽  
Small Subset ◽  
Nucleotide Polymorphisms ◽  
Healthy Individuals ◽  
Allelic Expression Imbalance ◽  
Single Nucleotide ◽  
Metabolic Traits ◽  
Genome Wide

abstract Context: Genome-wide association scans (GWAS) have identified novel single nucleotide polymorphisms (SNPs) that increase T2D susceptibility and indicated the role of nearby genes in T2D pathogenesis. Objective: We hypothesized that T2D-associated SNPs act as cis-regulators of nearby genes in human tissues and that expression of these transcripts may correlate with metabolic traits, including insulin sensitivity (SI). Design, Settings, and Patients: Association of SNPs with the expression of their nearest transcripts was tested in adipose and muscle from 168 healthy individuals who spanned a broad range of SI and body mass index (BMI) and in transformed lymphocytes (TLs). We tested correlations between the expression of these transcripts in adipose and muscle with metabolic traits. Utilizing allelic expression imbalance (AEI) analysis we examined the presence of other cis-regulators for those transcripts in TLs. Results: SNP rs9472138 was significantly (P = 0.037) associated with the expression of VEGFA in TLs while rs6698181 was detected as a cis-regulator for the PKN2 in muscle (P = 0.00027) and adipose (P = 0.018). Significant association was also observed for rs17036101 (P = 0.001) with expression of SYN2 in adipose of Caucasians. Among 19 GWAS-implicated transcripts, expression of VEGFA in adipose was correlated with BMI (r = −0.305) and SI (r = 0.230). Although only a minority of the T2D-associated SNPs were validated as cis-eQTLs for nearby transcripts, AEI analysis indicated presence of other cis-regulatory polymorphisms in 54% of these transcripts. Conclusions: Our study suggests that a small subset of GWAS-identified SNPs may increase T2D susceptibility by modulating expression of nearby transcripts in adipose or muscle.

scholarly journals Genome-Wide Association Study of Body Weight Traits in Chinese Fine-Wool Sheep

Animals ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 170 ◽  
Author(s):  
Zengkui Lu ◽  
Yaojing Yue ◽  
Chao Yuan ◽  
Jianbin Liu ◽  
Zhiqiang Chen ◽  
...  
Keyword(s):  
Body Weight ◽  
Muscle Development ◽  
Genome Wide Association Study ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genome Wide ◽  
Economic Trait ◽  
Significance Levels ◽  
Genomic Regions ◽  
Selection Of

Body weight is an important economic trait for sheep and it is vital for their successful production and breeding. Therefore, identifying the genomic regions and biological pathways that contribute to understanding variability in body weight traits is significant for selection purposes. In this study, the genome-wide associations of birth, weaning, yearling, and adult weights of 460 fine-wool sheep were determined using resequencing technology. The results showed that 113 single nucleotide polymorphisms (SNPs) reached the genome-wide significance levels for the four body weight traits and 30 genes were annotated effectively, including AADACL3, VGF, NPC1, and SERPINA12. The genes annotated by these SNPs significantly enriched 78 gene ontology terms and 25 signaling pathways, and were found to mainly participate in skeletal muscle development and lipid metabolism. These genes can be used as candidate genes for body weight in sheep, and provide useful information for the production and genomic selection of Chinese fine-wool sheep.

scholarly journals Variation rs9929218 and Risk of the Colorectal Cancer and Adenomas: A Meta-analysis

2020 ◽  
Author(s):  
Huiyan Wang ◽  
Dongying Gu ◽  
Miao Yu ◽  
Yanjun Hu ◽  
Zhe Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Colorectal ◽  
Association Studies ◽  
Meta Analysis ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Accurate Approximation ◽  
Single Nucleotide ◽  
Genome Wide ◽  
Different Populations

Abstract Backgrounds: Genome-wide association studies (GWAS) have identified multiple common CRC-related (colorectal cancer) SNPs (single nucleotide polymorphisms) including the Cadherin 1(CDH1) rs9929218 may act by increasing the risk of colorectal cancer, colorectal adenoma, or both. These studies, however, reported inconsistent associations. Methods: To derive a more accurate approximation of the connection, we carried out a meta-analysis of 12 published pieces of research including 11,590 controls and 8,192 cases. We used odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate the associations' strength.Results: Meta-analysis implied considerable association between CRC and rs9929218 (OR = 1.21, 95%CI 1.04-1.42 for GG versus AA; OR = 1.22, 95%CI 1.05-1.42 for GG/AG versus AA).In the subgroup analyses, significantly increased risks were found among Europeans.Conclusions: In summary, our meta-analysis studies in different populations confirmed that SNP rs9929218 is significantly associated with CRC risk and that this variant may have a greater impact on Europeans.

scholarly journals Single-nucleotide polymorphisms: a perspective of cardiovascular prevention

2015 ◽  
Vol 61 (5) ◽  
pp. 458-468 ◽  
Author(s):  
Guilherme Brasil Grezzana ◽  
José Luiz da Costa Vieira ◽  
Vera Lúcia Portal
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Cardiovascular Prevention ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Heart Attacks ◽  
Clinical Scenarios ◽  
Different Populations ◽  
Clinical Conditions

Summary Introduction: several studies have evaluated the utilization of lipid biomarkers in an attempt to correlate them with clinical cardiovascular events. Nevertheless, the investigation of clinical conditions under specific plasmatic levels of lipoproteins for long periods presents limitations due to inherent difficulties that are related to the follow-up of individuals throughout their lives. Better understanding of the clinical response and occasional resistance to the action of hypolipidemic drugs in several clinic scenarios is also necessary. Objectives: to determine the role of evaluation of single-nucleotide polymorphisms (SNPs) related to the metabolism of lipids, and its implications in different clinical scenarios. Methods: a search of the literature in English and Spanish languages was performed in Medline, Lilacs via Bireme, IBECS via Bireme, and Cochrane databases. The expected results included information regarding plasmatic lipid profile and SNPs, cardiovascular clinical outcomes and polymorphisms related to the effectiveness of statins in the treatment of hypercholesterolemia. Results: in order to perform this analysis, 19 studies were included from a total of 89 identified citations. The evaluation of the results suggests that low plasmatic levels of LDL-c are associated with a reduction in the risk of heart attacks, although this was not observed for the rise of plasmatic levels of HDL-c. Conclusion: polymorphisms in different populations and clinical perspectives may bring important contributions for a better understanding and adequacy of plasmatic lipoproteins aiming at reducing cardiovascular risk.

scholarly journals Prediction of Deleterious Single Nucleotide Polymorphisms in Human p53 Gene

2018 ◽  
Author(s):  
Saruar Alam ◽  
Mohammad Sayem ◽  
Md. Kamrul Hasan ◽  
Zinat Sharmin ◽  
Mahmud Arif Pavel ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Deleterious Effect ◽  
P53 Gene ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Computational Tools ◽  
Genome Wide ◽  
Project Hope ◽  
Functional Part ◽  
Different Populations

AbstractWith a variety of accessible Single Nucleotide Polymorphisms (SNPs) data on human p53 gene, this investigation is intended to deal with detrimental SNPs in p53 gene by executing diverse valid computational tools, including Filter, SIFT, PredictSNP, Fathmm, UTRScan, ConSurf, Phyre, Tm-Adjust, I-Mutant, Task Seek after practical and basic appraisal, dissolvable openness, atomic progression, and analysing the energy minimization. Of 581 p53 SNPs, 420 SNPs are found to be missense or non-synonymous and 435 SNPs are in the 3 prime UTR and 112 SNPs are of every 5 prime UTR from which 16 non synonymous SNPs (nsSNPs) as non-tolerable while PredictSNP package predicted 14 (taking consideration SNP colored green by two or more than 2 analyses is neutral). By concentrating on six bioinformatics tools of various dimensions a combined output is generated where 14 nsSNPs are prone to exert a deleterious effect. By using diverse SNP analysing tools we have found 5 missense SNPs in the 3 crucial amino acids position in the DNA binding domain. The underlying discoveries are fortified by I-Mutant and Project HOPE. The ExPASy-PROSITE tools characterized whether the mutations located in the functional part of the protein or not. This study provides a decisive outcome concluding the accessible SNPs information by recognizing the five harming nsSNPs: rs28934573 (S241F), rs11540652 (R248Q), rs121913342 (R248W), rs121913343 (R273C) and rs28934576 (R273H). The findings of this investigation recognize the detrimental nsSNPs which enhance the danger of various kinds of oncogenesis in patients of different populations’ in genome-wide studies (GWS).

scholarly journals Variation rs9929218 and risk of the colorectal Cancer and adenomas: A meta-analysis

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Huiyan Wang ◽  
Dongying Gu ◽  
Miao Yu ◽  
Yanjun Hu ◽  
Zhe Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Colorectal ◽  
Association Studies ◽  
Meta Analysis ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Accurate Approximation ◽  
Single Nucleotide ◽  
Genome Wide ◽  
Different Populations

Abstract Backgrounds Genome-wide association studies (GWAS) have identified multiple common CRC-related (colorectal cancer) SNPs (single nucleotide polymorphisms) including the Cadherin 1(CDH1) rs9929218 may act by increasing the risk of colorectal cancer, colorectal adenoma, or both. These studies, however, reported inconsistent associations. Methods To derive a more accurate approximation of the connection, we carried out a meta-analysis of 12 published pieces of research including 11,590 controls and 8192 cases. We used odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate the associations’ strength. Results Meta-analysis implied considerable association between CRC and rs9929218 (OR = 1.21, 95%CI 1.04–1.42 for GG versus AA; OR = 1.22, 95%CI 1.05–1.42 for GG/AG versus AA). In the subgroup analyses, significantly increased risks were found among Europeans. Conclusions In summary, our meta-analysis studies in different populations confirmed that SNP rs9929218 is significantly associated with CRC risk and that this variant may have a greater impact on Europeans.

scholarly journals Genetic Mutation Analysis of High and Low IgY Chickens by Capture Sequencing

Animals ◽  
2019 ◽  
Vol 9 (5) ◽  
pp. 272 ◽  
Author(s):  
Qiao Wang ◽  
Fei Wang ◽  
Lu Liu ◽  
Qinghe Li ◽  
Ranran Liu ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Genetic Mutation ◽  
Genetic Mutations ◽  
Nucleotide Polymorphisms ◽  
White Leghorn ◽  
Single Nucleotide ◽  
Synonymous Mutations ◽  
Genome Wide ◽  
Genomic Regions ◽  
Capture Sequencing

Based on the results of our previous genome-wide association study (GWAS), a comprehensive analysis on single nucleotide polymorphisms (SNPs) was performed on White Leghorn and Beijing-You chickens with high and low IgY levels in defined genomic regions using the capture-sequencing approach. High and low IgY chickens showed substantial genetic variations. In total, more than 30,000 SNPs were found in all four chicken groups, among which 1045 were non-synonymous mutations resulting in amino acids alterations. In total, 23,309 Indels were identified. Among the 1169 Indels that were found only in Beijing-You chickens, 702 were shared between high and low IgY chickens compared with the reference genome. There were 1016 Indels specific to the White Leghorn chickens, among which 188 were high IgY-specific, 134 were low IgY-specific and 694 were shared between the high and low IgY chicken lines. Many genetic mutations were located in the regulatory regions of important immunomodulatory genes, including TAP1, TAP2 and BF1. Our findings provide an in-depth understanding of genetic mutations in chicken microchromosomes.

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