Genes Regulating Immune Response and Amelogenesis Interact in Increasing the Susceptibility to Molar-Incisor Hypomineralization

2018 ◽  
Vol 53 (2) ◽  
pp. 217-227 ◽  
Author(s):  
Diego Girotto Bussaneli ◽  
Manuel Restrepo ◽  
Camila Maria Bullio Fragelli ◽  
Lourdes Santos-Pinto ◽  
Fabiano Jeremias ◽  
...  
Keyword(s):  
Immune Response ◽  
Gene Interactions ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Nuclear Families ◽  
Molar Incisor Hypomineralization ◽  
Inflammatory Stimuli ◽  
Allele Specific ◽  
Family Based ◽  
And Function

Ameloblasts are sensitive cells whose metabolism and function may be affected by inflammatory stimuli. The aim of this study was to evaluate the possible association between polymorphisms in immune response-related genes and molar-incisor hypomineralization (MIH), and their interaction with polymorphisms in amelogenesis-related genes. DNA samples were obtained from 101 nuclear families that had at least 1 MIH-affected child. Eleven single-nucleotide polymorphisms (SNPs) were investigated in immune response genes using TaqMan® technology allele-specific probes. A transmission disequilibrium test was performed to verify overtransmission of alleles in all MIH families, as well as in families only with mild or severe MIH-affected children. Gene-gene interactions between the immune-related and amelogenesis-related polymorphisms were analyzed by determining whether alleles of those genes were transmitted from heterozygous parents more often in association than individually with MIH-affected children. In severe cases of MIH, significant results were observed for rs10733708 (TGFBR1, OR = 3.5, 95% CI = 1.1–10.6). Statistical evidence for gene-gene interactions between rs6654939 (AMELX) and the SNPs rs2070874 (IL4), rs2275913 (IL17A), rs1800872 (IL10), rs1800587 (IL1A), and rs3771300 (STAT1) was observed. The rs2070874 SNP (IL4) was also significantly overtransmitted from heterozygous parents with the rs7526319 (TUFT1) and the rs2355767 (BMP2) SNPs, suggesting a synergistic effect of the transmission of these alleles with susceptibility to MIH. This family-based study demonstrated an association between variation in TGFBR1 and MIH. Moreover, the polymorphisms in immune response and amelogenesis genes may have an additive effect on the risk of developing MIH.

scholarly journals TNF-α -308G/A polymorphism and susceptibility to tuberculosis in Azeri population of Iran

Genetika ◽  
2016 ◽  
Vol 48 (3) ◽  
pp. 819-826 ◽  
Author(s):  
Sajjad Ghorghanlu ◽  
Mohammad Asgharzadeh ◽  
Hossein Samadi-Kafil ◽  
Fatemeh Khaki-Khatibi ◽  
Jalil Rashedi ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Tuberculosis Patient ◽  
P Value ◽  
Nucleotide Polymorphisms ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Tuberculosis Patients ◽  
Specific Pcr ◽  
Allele Specific ◽  
And Function

Single nucleotide polymorphisms (SNPs) in cytokine genes may alter the level and function of secreted cytokine; therefore, SNPs can influence the immune response. The aim of the present study was to determine the association of TNF-? -308G/A single nucleotide polymorphism in tuberculosis patients in the Azeri population of Iran. The TNF-308G/A single nucleotide polymorphism in the promoter region was genotyped by using the allele-specific PCR method in 200 healthy controls and 124 tuberculosis patients. The distribution of allele frequencies for TNF-? -308G/A polymorphism between control and tuberculosis patient groups was not significant (P-value = 0.058, OR = 1.5). Furthermore, no statistically significant association was found between TNF-? -308G/A genotype and resistance/susceptibility to TB (P-value = 0.102). Our results suggest that TNF-? -308G/A polymorphism has no measurable effect on the development of tuberculosis in Azeri population of Iran.

scholarly journals Genetic Variation Underpinning ADHD Risk in a Caribbean Community

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 907
Author(s):  
Pedro J. Puentes-Rozo ◽  
Johan E. Acosta-López ◽  
Martha L. Cervantes-Henríquez ◽  
Martha L. Martínez-Banfi ◽  
Elsy Mejia-Segura ◽  
...  
Keyword(s):  
Neurodevelopmental Disorder ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genetic Studies ◽  
Nuclear Families ◽  
Caribbean Community ◽  
Hyperactivity Disorder ◽  
Potential Association ◽  
Family Based ◽  
Genetic Stratification

Attention Deficit Hyperactivity Disorder (ADHD) is a highly heritable and prevalent neurodevelopmental disorder that frequently persists into adulthood. Strong evidence from genetic studies indicates that single nucleotide polymorphisms (SNPs) harboured in the ADGRL3 (LPHN3), SNAP25, FGF1, DRD4, and SLC6A2 genes are associated with ADHD. We genotyped 26 SNPs harboured in genes previously reported to be associated with ADHD and evaluated their potential association in 386 individuals belonging to 113 nuclear families from a Caribbean community in Barranquilla, Colombia, using family-based association tests. SNPs rs362990-SNAP25 (T allele; p = 2.46 × 10−4), rs2282794-FGF1 (A allele; p = 1.33 × 10−2), rs2122642-ADGRL3 (C allele, p = 3.5 × 10−2), and ADGRL3 haplotype CCC (markers rs1565902-rs10001410-rs2122642, OR = 1.74, Ppermuted = 0.021) were significantly associated with ADHD. Our results confirm the susceptibility to ADHD conferred by SNAP25, FGF1, and ADGRL3 variants in a community with a significant African American component, and provide evidence supporting the existence of specific patterns of genetic stratification underpinning the susceptibility to ADHD. Knowledge of population genetics is crucial to define risk and predict susceptibility to disease.

scholarly journals Brain-derived neurotrophic factor (BDNF) gene and rapid-cycling bipolar disorder

2006 ◽  
Vol 189 (4) ◽  
pp. 317-323 ◽  
Author(s):  
Daniel J. Müller ◽  
Vincenzo De Luca ◽  
Tricia Sicard ◽  
Nicole King ◽  
John Strauss ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Rapid Cycling ◽  
Nucleotide Polymorphisms ◽  
Bdnf Gene ◽  
Single Nucleotide ◽  
Nuclear Families ◽  
Family Based ◽  
The Brain

BackgroundWe have previously reported the Val66Met and GT(n) repeat polymorphisms of the brain-derived neurotrophic factor (BDNF) gene to be associated with bipolar disorder. However, these findings have not been replicated consistently.AimsTo dissect the association of the BDNF gene with bipolar disorder by examining additional markers at the DNA level and by testing the illness categories of bipolar disorder I and II and rapid cycling.MethodWe performed a family-based association study and haplotype analyses with 312 nuclear families using four single nucleotide polymorphisms (SNPs) and the Val66Met and GT(n) repeat polymorphisms.ResultsThe SNPs hCVI1592756 and rs2049045, the Val66Met and GT(n) were significantly associated with bipolar disorder using transmission disequilibrium analyses (P=0.02, 0.009, 0.001 and 0.008 respectively). The effect at these markers was mainly driven by the rapid-cycling patients.ConclusionsWithin bipolar disorder, variation in the BDNF gene appears to predict risk for developing rapid cycling according to DSM–IV. Incorporating this clinical sub-phenotyping into other studies of the BDNF gene may help to resolve some of the inconsistencies reported thus far concerning BDNF and bipolar disorder.

scholarly journals Investigation of allele specific expression in various tissues of broiler chickens using the detection tool VADT

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
M. Joseph Tomlinson ◽  
Shawn W. Polson ◽  
Jing Qiu ◽  
Juniper A. Lake ◽  
William Lee ◽  
...  
Keyword(s):  
Broiler Chickens ◽  
Nucleotide Polymorphisms ◽  
Rna Seq ◽  
Specific Expression ◽  
Single Nucleotide ◽  
Allele Specific Expression ◽  
Detection Tool ◽  
Commercial Broiler ◽  
Significant Phenomenon ◽  
Allele Specific

AbstractDifferential abundance of allelic transcripts in a diploid organism, commonly referred to as allele specific expression (ASE), is a biologically significant phenomenon and can be examined using single nucleotide polymorphisms (SNPs) from RNA-seq. Quantifying ASE aids in our ability to identify and understand cis-regulatory mechanisms that influence gene expression, and thereby assist in identifying causal mutations. This study examines ASE in breast muscle, abdominal fat, and liver of commercial broiler chickens using variants called from a large sub-set of the samples (n = 68). ASE analysis was performed using a custom software called VCF ASE Detection Tool (VADT), which detects ASE of biallelic SNPs using a binomial test. On average ~ 174,000 SNPs in each tissue passed our filtering criteria and were considered informative, of which ~ 24,000 (~ 14%) showed ASE. Of all ASE SNPs, only 3.7% exhibited ASE in all three tissues, with ~ 83% showing ASE specific to a single tissue. When ASE genes (genes containing ASE SNPs) were compared between tissues, the overlap among all three tissues increased to 20.1%. Our results indicate that ASE genes show tissue-specific enrichment patterns, but all three tissues showed enrichment for pathways involved in translation.

In Silico Identification of Novel Acute Myeloid Leukemia Associated Missense SNPs in Human CEBPA Gene

2020 ◽  
pp. 10-24
Keyword(s):  
Acute Myeloid Leukemia ◽  
In Silico ◽  
Myeloid Leukemia ◽  
Gene Interaction ◽  
Nucleotide Polymorphisms ◽  
Future Perspectives ◽  
Single Nucleotide ◽  
In Silico Identification ◽  
And Function ◽  
Acute Myeloid

Single nucleotide polymorphisms (SNPs) in CEBPA gene have been found to be associated with cancer especially Acute Myeloid Leukemia (AML). Therefore, the identification of functional and structural polymorphisms in CEBPA is important to study and discover therapeutics targets and potential malfunctioning. For this purpose, several bioinformatics tools were used for the identification of disease-associated nsSNPs, which might be vital for the structure and function of CEBPA, making them extremely important. In silico tools used in this study included SIFT, PROVEAN, PolyPhen2, SNP&GO and PhD-SNP, followed by ConSurf and I-Mutant. Protein 3D modelling was carried out using I-TASSER and MODELLER v9.22, while GeneMANIA and string were used for the prediction of gene-gene interaction in this regard. From our study, we found that the L345P, R333C, R339Q, V328G, R327W, L317Q, N292S, E284A, R156W, Y108N and F82L mutations were the most crucial SNPs. Additionally, the gene-gene interaction showed the genes having correlation with CEBPA’s co-expressions and importance in several pathways. In future, these 11 mutations should be investigated while studying diseases related to CEBPA, especially for AML. Being the first of its kind, future perspectives are proposed in this study, which will help in precision medicine. Animal models are of great significance in finding out CEBPA effects in disease.

scholarly journals A Novel Test System for Genotyping rs43703016 Single-nucleotide Substitutions in the Bovine CSN3 Gene

2019 ◽  
pp. 1-5
Author(s):  
Svetlana Kovalchuk ◽  
Arina Tagmazyan ◽  
Eugene Klimov
Keyword(s):  
Nucleotide Substitution ◽  
Milk Proteins ◽  
Test System ◽  
Nucleotide Polymorphisms ◽  
Dna Testing ◽  
Nucleotide Substitutions ◽  
Single Nucleotide ◽  
Allele Specific ◽  
Selection Of

Aims: Caseins are among the main milk proteins that determine many of its properties. Bovine kappa-casein (CSN3) is associated with the qualitative composition of milk, as well as with the quality of cheese obtained from this milk. The rs43703016 single-nucleotide substitution (g.88532332A>C; Asp148Ala) in exon 4 of the bovine CSN3 gene plays an important role in the production of quality hard cheeses. Various methods for the DNA testing of this substitution have been developed in the last three decades. Emergent DNA technologies provide an opportunity to modernize methods of genotyping single-nucleotide polymorphisms. Results: We have developed and verified a method to differentiate A/C alleles of the rs43703016 substitution in the bovine CSN3 gene by real-time PCR using allele-specific fluorescent probes. Conclusion: Our new method allows fast genotyping of animals, and may be used for selection of cows carrying the CC genotype, which determines good cheese-making properties of milk.

Timing during translation matters: synonymous mutations in human pathologies influence protein folding and function

2018 ◽  
Vol 46 (4) ◽  
pp. 937-944 ◽  
Author(s):  
Robert Rauscher ◽  
Zoya Ignatova
Keyword(s):  
Protein Folding ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Synonymous Mutations ◽  
Translation Velocity ◽  
Disease Penetrance ◽  
And Function ◽  
Related Proteins ◽  
Translational Speed ◽  
Fine Tune

Ribosomes translate mRNAs with non-uniform speed. Translation velocity patterns are a conserved feature of mRNA and have evolved to fine-tune protein folding, expression and function. Synonymous single-nucleotide polymorphisms (sSNPs) that alter programmed translational speed affect expression and function of the encoded protein. Synergistic advances in next-generation sequencing have led to the identification of sSNPs associated with disease penetrance. Here, we draw on studies with disease-related proteins to enhance our understanding of mechanistic contributions of sSNPs to functional alterations of the encoded protein. We emphasize the importance of identification of sSNPs along with disease-causing mutations to understand genotype–phenotype relationships.

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