scholarly journals Computational Analysis of Single Nucleotide polymorphisms (SNPs) in Human TCell Acute Lymphocytic Leukemia Protein 1 (TAL1) Gene/Comprehensive Study

2018 ◽  
Author(s):  
Shaza W. Shantier ◽  
Hashim E. Elmansi ◽  
Mihad E. Elnnewery ◽  
Hind K. Osman ◽  
Isam-Aldin A. Alhassan ◽  
...  
Keyword(s):  
Protein Function ◽  
Computational Analysis ◽  
Lymphocytic Leukemia ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Post Translational Modifications ◽  
Diamond Blackfan Anemia ◽  
Helix Loop Helix ◽  
Therapeutic Measures ◽  
Near Future

AbstractBackgroundTAL1is a proto-oncogene whose distorted modifications in committed T-cell Precursors is related with the development of T-ALL, it also found to be related to many other human hematological diseases such as lymphoblastic lymphoma, immunodeficiency 18, acute myeloid leukemia and diamond-blackfan Anemia.ObjectivesThis study aims to predict the effect of nsSNPs onTAL1protein structure functionMethodsRetrieved nSNPs in the coding and3’UTRregions were analyzed using different in silico tools. Interactions ofTAL1with functionally similar genes were investigated using Genemania. Post-translational modifications in several sites of the protein were also investigated.ResultsOut of ninety nsSNPs identified, only eight were found damaging to protein function of which one is located in the basis helix-loop-helix domain (bHLH). Two SNPs were anticipated by PolymiRTs to prompt disturbance or creation of miR binding sites.ConclusionThe present study is the first ever computational analysis ofTAL1’s nsSNPs hence this effort might be of help in the near future for inventing early diagnostic and therapeutic measures for T-ALL

scholarly journals The Glucocorticoid Receptor Polymorphism Landscape in Patients With Diamond Blackfan Anemia Reveals an Association Between Two Clinically Relevant Single Nucleotide Polymorphisms and Time to Diagnosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Annalisa Lonetti ◽  
Valentina Indio ◽  
Irma Dianzani ◽  
Ugo Ramenghi ◽  
Lydie Da Costa ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Glucocorticoid Receptor ◽  
Compensatory Mechanism ◽  
Nucleotide Polymorphisms ◽  
Disease Manifestation ◽  
Single Nucleotide ◽  
Diamond Blackfan Anemia ◽  
Glucocorticoid Response ◽  
Minor Alleles ◽  
Population Demographic

NR3C1, the gene encoding the glucocorticoid receptor, is polymorphic presenting numerous single nucleotide polymorphisms (SNPs) some of which are emerging as leading cause in the variability of manifestation and/or response to glucocorticoids in human diseases. Since 60–80% of patients with Diamond Blackfan anemia (DBA), an inherited pure red cell aplasia induced by mutations in ribosomal protein genes became transfusion independent upon treatment with glucocorticoids, we investigated whether clinically relevant NR3C1 SNPs are associated with disease manifestation in DBA. The eight SNPs rs10482605, rs10482616, rs7701443, rs6189/rs6190, rs860457, rs6198, rs6196, and rs33388/rs33389 were investigated in a cohort of 91 European DBA patients. Results were compared with those observed in healthy volunteers (n=37) or present in public genome databases of Italian and European populations. Although, cases vs. control analyses suggest that the frequency of some of the minor alleles is significantly altered in DBA patients with respect to healthy controls or to the Italian or other European registries, lack of consistency among the associations across different sets suggests that overall the frequency of these SNPs in DBA is not different from that of the general population. Demographic data (47 females and 31 males) and driver mutations (44 S and 29 L genes and eight no-known mutation) are known for 81 patients while glucocorticoid response is known, respectively, for 81 (36 responsive and 45 non-responsive) and age of disease onsets for 79 (55 before and 24 after 4months of age) patients. Neither gender nor leading mutations were associated with the minor alleles or with disease manifestation. In addition, none of the SNPs met the threshold in the response vs. non-responsive groups. However, two SNPs (rs6196 and rs860457) were enriched in patients manifesting the disease before 4months of age. Although the exact biomechanistical consequences of these SNPs are unknown, the fact that their configuration is consistent with that of regulatory regions suggests that they regulate changes in glucocorticoid response during ontogeny. This hypothesis was supported by phosphoproteomic profiling of erythroid cells expanded ex vivo indicating that glucocorticoids activate a ribosomal signature in cells from cord blood but not in those from adult blood, possibly providing a compensatory mechanism to the driving mutations observed in DBA before birth.

scholarly journals Prediction of Structural and Functional Effects of Single Nucleotide Polymorphisms in <i>NAT2</i>gene, a Computational Analysis

2019 ◽  
Vol 7 (4) ◽  
pp. 88
Author(s):  
Amna Elsadig Elsafi Abodlaa ◽  
Dalia Mursi ◽  
Mona Abdelrahman Mohamed Khaier ◽  
Mai Abdul RahmanMasri ◽  
Nazik Elmalaika Obaid Seid Ahmed Husain ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Computational Analysis ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

scholarly journals Computational analysis of functional single nucleotide polymorphisms associated with SLC26A4 gene

PLoS ONE ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. e0225368
Author(s):  
Mirza Jawad Ul Hasnain ◽  
Muhammad Shoaib ◽  
Salman Qadri ◽  
Bakhtawar Afzal ◽  
Tehreem Anwar ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Computational Analysis ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Slc26a4 Gene

Prognostic Assessment of Three Single Nucleotide Polymorphisms (BCL2–938C>A, MTHFR 677C>T, GNAS1 T393C) in Chronic Lymphocytic Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2080-2080
Author(s):  
Thorsten Zenz ◽  
Ulrich Duehrsen ◽  
Harald Dohner ◽  
Winfried Siffert ◽  
Stephan Stilgenbauer ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Single Nucleotide Polymorphisms ◽  
Molecular Genetics ◽  
Association Studies ◽  
Lymphocytic Leukemia ◽  
Allele Frequencies ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Gnas1 T393c

Abstract A number of single nucleotide polymorphisms (SNP) have been implicated to impact on the disease course in chronic lymphocytic leukemia (CLL). Nonetheless, there have been few polymorphisms for which replications of association were done in different studies. We genotyped three recently described SNPs (BCL2 –938C&gt;A, MTHFR 677C&gt;T, GNAS1 T393C) in a large group of CLL patients (n=273) with mature follow up and detailed analysis of molecular genetics. The cohort had a median follow-up of over 150 months and the known poor risk molecular genetics (17p–, 11q– and unmutated VH-status) were associated with poor prognosis. The allele frequencies for all three SNPs were in Hardy Weinberg equilibrium and we could not identify imbalances when we stratified for subgroups (genomic aberrations, VH status, stage according to Binet). Moreover, the polymorphisms did not affect clinical outcome (time to first treatment and overall survival) in univariate or multivariate analysis in the current cohort. Comparing CLL patients with over 100 healthy controls we found no significant differences in allele frequencies or genotype distributions for all three polymorphisms. While there have been reports showing the molecular effects and clinical consequences of the polymorphisms we studied, we did not find SNP genotype-dependent effects in a large cohort of CLL patients. Potential reasons for the discrepancy of the results are numerous. Because of the advancement of genotyping technologies, a large number of SNPs can be evaluated (multiple testing). The sample sizes of the reported association studies are often too small and frequently only one patient cohort is investigated. Moreover, negative results are often not published (publication bias). One major reason for the different results is the different genetic background of the populations due to ethnicity (selection bias). Summarized, this study supports the importance of confirmation of initial findings in an independent data set. However, results of genome-wide association studies will soon be reported with additional novel genes identified and will help making great strides in identifying the genetic determinants of CLL risk.

Inherited genetic susceptibility to monoclonal B-cell lymphocytosis

Blood ◽  
2010 ◽  
Vol 116 (26) ◽  
pp. 5957-5960 ◽  
Author(s):  
Dalemari Crowther-Swanepoel ◽  
Tanguy Corre ◽  
Amy Lloyd ◽  
Gianluca Gaidano ◽  
Bianca Olver ◽  
...  
Keyword(s):  
Genetic Variation ◽  
B Cell ◽  
Odds Ratio ◽  
Case Control ◽  
Lymphocytic Leukemia ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Control Series ◽  
Inherited Predisposition ◽  
The Impact

Abstract Monoclonal B-cell lymphocytosis (MBL) is detectable in &gt; 3% of the general population. Recent data are compatible, at least in a proportion of cases, with MBL being a progenitor lesion for chronic lymphocytic leukemia (CLL) and a surrogate for inherited predisposition. Common single nucleotide polymorphisms (SNPs) at 2q13 (rs17483466), 2q37.1 (rs13397985), 2q37.3 (rs757978), 6p25.3 (rs872071), 8q24.21 (rs2456449), 11q24.1 (rs735665), 15q21.3 (rs7169431), 15q23 (rs7176508), 16q24.1 (rs305061), and 19q13.32 (rs11083846) have been shown to confer a modest but significant increase in CLL risk. To examine the impact of these 10 SNPs on MBL, we analyzed 3 case-control series totaling 419 cases and 1753 controls. An association between genotype and MBL risk was seen for 9 SNPs, 6 of which were statistically significant: rs17483466 (odds ratio [OR] =1.27; P = .02), rs13397985 (OR = 1.40; P = 1.72 × 10−3), rs757978 (OR = 1.38; P = .02), rs872071 (OR = 1.27; P = 7.75 × 10−3), rs2456449 (OR = 1.31; P = 3.14 × 10−3), and rs735665 (OR = 1.63; P = 6.86 × 10−6). Collectively, these data provide support for genetic variation influencing CLL risk through predisposition to MBL.

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