Characterization Of a Weakly Expressed KIR2DL1 Allele

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4847-4847
Author(s):  
Hongchuan Li ◽  
Andrew R Huehn ◽  
Postbaccalaureate Fellow ◽  
Paul W Wright ◽  
Research Biologist ◽  
...  
Keyword(s):  
Single Copy ◽  
Surface Expression ◽  
Genetic Alterations ◽  
Proximal Promoter ◽  
Nucleotide Polymorphisms ◽  
Coding Region ◽  
Class I Mhc ◽  
Complete Sequencing ◽  
Weak Expression ◽  
Distal Promoter

Abstract The variegated expression of the human KIR family of class I MHC receptors provides an interesting model system for the study of stochastic activation of gene transcription. Previous studies have linked distal KIR promoter transcription to the initiation of KIR expression from the proximal promoter. In order to identify novel genetic alterations associated with decreased KIR expression, a group of 182 donors was characterized for KIR gene content, KIR transcripts, and FACS analysis of KIR surface expression. An individual was discovered that possessed a single copy of the KIR2DL1 gene but had a low level of gene expression by either FACS or Q-PCR.  Complete sequencing of the KIR2DL1 gene confirmed the presence of an intact coding region. Analysis of promoter elements revealed a cluster of three single nucleotide polymorphisms (SNPs) in the distal promoter approximately 1 kb upstream from the start of KIR2DL1 translation. These SNPs are also found in the distal promoter region of the non-transcribed KIR2DL5*002 allele as well as the KIR3DP1 pseudogene. One of these SNPs creates a functional binding site for the ZEB1 transcription factor.  Individuals possessing the ZEB1 site in their KIR2DL1 promoter produce high levels of a non-translatable distal KIR2DL1transcript that inhibits transcription from the proximal promoter, resulting in weak expression of this allele. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. Funded by NCI Contract HHSN261200800001E. Disclosures: Miller: Coronado Biosciences: Scientific Advisory Board Other.

scholarly journals THE EFFECT OF SINGLE NUCLEOTIDE POLYMORPHISM (SNP) IN GLIOBLASTOMA MULTIFORME

2021 ◽  
Author(s):  
Asmita Ghosh ◽  
Dattatreya Mukherjee ◽  
Parth Patel ◽  
Debraj Mukhopadhyay
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Glioblastoma Multiforme ◽  
Association Studies ◽  
Disease Onset ◽  
Genetic Alterations ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Coding Region ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide

Single nucleotide polymorphism is a genetic substitution of a base pair at a single position of the genome. SNPs are a common phenomenon and influence mRNA expression. Half of the SNPs occur in the non-coding region with 25% being mis-sense mutation and 25% being silent mutations. SNPs belong to the last generation of molecular markers which is identified through SNP mapping. SNPs are extensively studied to distinguish genetic expression and protein synthesis. These genetic differences are a major source of diseases in humans like cancers. One of the most common types of cancer of the brain is the Glioblastoma Multiforme that accounts for more than 80% of the malignant primary brain tumors (PBT). Researchers have found out a potential role of various SNPs in the genome to have a strong relation with Glioma formation and proliferation. Most SNPs are either not discovered, or their biological mechanisms are unknown, making it difficult to link putative associations with disease onset. The given review aims to identify some of the most common SNPs associated with GBM and classify the genetic basis along with future prospects. These SNPs are pioneer in Genome Wide Association studies to help in cancer research and identification of specific genetic alterations liked to GBM. Single Nucleotide Polymorphisms in a gene can be used as genetic biomarkers to aid better understanding of the mechanism of cancer formation, its aetiology, progression and metastatic behaviour.

scholarly journals Glyoxalase 1 gene improves the antistress capacity and reduces the immune inflammatory response

BMC Genetics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Fukuan Du ◽  
Yan Li ◽  
Jing Shen ◽  
Yueshui Zhao ◽  
Parham Jabbarzadeh Kaboli ◽  
...  
Keyword(s):  
Sudden Death ◽  
Inflammatory Response ◽  
Protein Expression ◽  
Antioxidant Capacity ◽  
Single Copy ◽  
Dimensional Structure ◽  
Nucleotide Polymorphisms ◽  
Coding Region ◽  
Immune Mediated ◽  
Mrna And Protein Expression

Abstract Background Fish immunity is not only affected by the innate immune pathways but is also triggered by stress. Transport and loading stress can induce oxidative stress and further activate the immune inflammatory response, which cause tissue damage and sudden death. Multiple genes take part in this process and some of these genes play a vital role in regulation of the immune inflammatory response and sudden death. Currently, the key genes regulating the immune inflammatory response and the sudden death caused by stress in Coilia nasus are unknown. Results In this study, we studied the effects of the Glo1 gene on stress, antioxidant expression, and immune-mediated apoptosis in C. nasus. The full-length gene is 4356 bp, containing six exons and five introns. Southern blotting indicated that Glo1 is a single-copy gene in the C. nasus genome. We found two single-nucleotide polymorphisms (SNPs) in the Glo1 coding region, which affect the three-dimensional structure of Glo1 protein. An association analysis results revealed that the two SNPs are associated with stress tolerance. Moreover, Glo1 mRNA and protein expression of the heterozygous genotype was significantly higher than that of the homozygous genotype. Na+ and sorbitol also significantly enhanced Glo1 mRNA and protein expression, improved the fish’s antioxidant capacity, and reduced the immune inflammatory response, thus sharply reducing the mortality caused by stress. Conclusions Glo1 plays a potential role in the stress response, antioxidant capacity, and immune-mediated apoptosis in C. nasus.

scholarly journals Polymorphism Detection of GDF9 Gene and Its Association with Litter Size in Luzhong Mutton Sheep (Ovis aries)

Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 571
Author(s):  
Fengyan Wang ◽  
Mingxing Chu ◽  
Linxiang Pan ◽  
Xiangyu Wang ◽  
Xiaoyun He ◽  
...  
Keyword(s):  
Litter Size ◽  
Tertiary Structure ◽  
Novel Mutation ◽  
Major Gene ◽  
Ovis Aries ◽  
Nucleotide Polymorphisms ◽  
Economic Traits ◽  
Coding Region ◽  
Association Analyses ◽  
Gdf9 Gene

Litter size is one of the most important economic traits in sheep. GDF9 and BMPR1B are major genes affecting the litter size of sheep. In this study, the whole coding region of GDF9 was sequenced and all the SNPs (single nucleotide polymorphisms) were determined in Luzhong mutton ewes. The FecB mutation was genotyped using the Sequenom MassARRAY®SNP assay technology. Then, the association analyses between polymorphic loci of GDF9 gene, FecB, and litter size were performed using a general linear model procedure. The results showed that eight SNPs were detected in GDF9 of Luzhong mutton sheep, including one novel mutation (g.41769606 T > G). The g.41768501A > G, g.41768485 G > A in GDF9 and FecB were significantly associated with litter size in Luzhong mutton ewes. The g.41768485 G > A is a missense mutation in the mature GDF9 protein region and is predicted to affect the tertiary structure of the protein. The results preliminarily demonstrated that GDF9 was a major gene affecting the fecundity of Luzhong mutton sheep and the two loci g.41768501A > G and g.41768485 G > A may be potential genetic markers for improving litter size.

Sequence variants in the FcεRI alpha chain gene

2002 ◽  
Vol 93 (1) ◽  
pp. 37-41 ◽  
Author(s):  
Toshiki Shikanai ◽  
Eric S. Silverman ◽  
Brian W. Morse ◽  
Craig M. Lilly ◽  
Hiroshi Inoue ◽  
...  
Keyword(s):  
Promoter Region ◽  
Population Substructure ◽  
Chain Gene ◽  
Polymorphism Analysis ◽  
Sequence Variants ◽  
Nucleotide Polymorphisms ◽  
Coding Region ◽  
Alpha Chain ◽  
Asthmatic Patients ◽  
Single Stranded Conformational Polymorphism

There is a relationship between IgE levels and expression of high-affinity IgE receptors (FcεRI). Because the alpha chain is the only portion of the receptor that binds directly to IgE, we reasoned that sequence variants in the FcεRI alpha gene may exist that alter these binding events. We screened all of the exons and the promoter region of the FcεRI alpha chain gene with genomic DNA from 389 asthmatic and 341 normal control subjects for mutations by using single-stranded conformational polymorphism analysis. No nonsynonomous single nucleotide polymorphisms (SNPs) were identified in the coding region. Three SNPs were found in the promoter region: an A/C transversion at −770 from the translation start site; a G/A transition at −664; and a T/C transition at −335. No differences in allele frequencies were detected between asthmatic subjects and controls. Homozygosity for the C variant at locus −335 was more common in Caucasian asthmatic patients with IgE levels in the lower quartile than in the upper quartile ( P = 0.032). An analysis of highly polymorphic SNPs indicated that this association is unlikely to be due to population substructure. We conclude that homozygosity for the C allele of FcεRI alpha chain variant is associated with lower IgE levels.

Single nucleotide polymorphisms of CBF4 locus region of Arabidopsis thaliana correspond to drought tolerance

2004 ◽  
Vol 1 (3) ◽  
pp. 181-190 ◽  
Author(s):  
Hao Gang-Ping ◽  
Wu Zhong-Yi ◽  
Chen Mao-Sheng ◽  
Cao Ming-Qing ◽  
Dominique Brunel ◽  
...  
Keyword(s):  
Arabidopsis Thaliana ◽  
Drought Tolerance ◽  
World Wide ◽  
Nucleotide Variation ◽  
Nucleotide Polymorphisms ◽  
Water Deficiency ◽  
Coding Region ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Adaptation To Drought

AbstractThe levels of drought tolerance and nucleotide polymorphism at the CBF4 locus were examined in a world-wide sample of 17 core accessions of Arabidopsis thaliana. The results showed that different accessions exhibited considerable differences in adaptation to drought stress. Compared with Columbia accession, the frequency of nucleotide polymorphism at the CBF4 locus of 25av, 203av and 244av accessions, including single nucleotide polymorphism (SNP) and insertion/deletion (Indel), was high, on average 1 SNP per 35.8 bp and 1 Indel per 143 bp. No significance in all regions of Tajima's D test indicated that the neutral mutation hypothesis could explain the nucleotide polymorphism in this CBF4 gene region. The higher polymorphism was the result of purification selection. Nucleotide polymorphism in the non-coding region was three times higher than in the coding region. This might indicate a recent relaxation of selection pressures on the non-coding region of CBF4 gene. In the coding region of CBF4, SNP frequency was 1 SNP per 96.4 bp and one non-synonymous mutation was detected from 25av, 203av and 244av accessions: the amino acid variation gly↔val at position 205, caused by the nucleotide variation G↔T at position 1034 (corresponding to the nucleotide at position 19 696 of GenBank accession no. AB015478 as 1). Furthermore, four differential SNPs were discovered in haplotype 6 constituted by 203av, one of them located in the 3′ non-coding region (A↔C at position 1106) and the others in the 5′ non-coding region (A↔G, A↔C and G↔A at positions 27, 129 and 171, respectively). The drought tolerance assay indicated that accession 203av was the best at tolerating water deficiency. We propose that haplotype 6 is consistent with its drought tolerance.

GENETIC VARIATION IN RARE AND WIDESPREAD LOMATIUM SPECIES (APIACEAE): A COMPARISON OF AFLP AND SSCP DATA

2001 ◽  
Vol 58 (2) ◽  
pp. 347-356 ◽  
Author(s):  
M. A. GITZENDANNER ◽  
P. S. SOLTIS
Keyword(s):  
Rare Species ◽  
Nucleotide Diversity ◽  
Nuclear Dna ◽  
Allelic Variation ◽  
Plant Conservation ◽  
Single Copy ◽  
Small Populations ◽  
Nucleotide Polymorphisms ◽  
Widespread Species ◽  
Low Levels

Plant conservation genetics has been hampered by a lack of markers for studies of levels and patterns of variation in rare species. We investigated the levels of variation in several rare and widespread species of the western North American genus Lomatium Raf. (Apiaceae) using two relatively new molecular markers: AFLPs and single-strand conformation polymorphisms (SSCPs). For each species, approximately 150 AFLP loci have been scored, yielding estimates of species-level percent polymorphic loci in rare species ranging from near zero to over 80%. Levels of AFLP diversity were similar in two of the rare species, L. bradshawii (Rose ex Mathias) Mathas & Constance and L. ochocense Helliwell & Constance, and the widespread species. The third rare species, L. cookii Kagan, which has small populations, has low levels of diversity based on AFLPs. We also examined nucleotide diversity at the single-copy nuclear-DNA locus glyceraldehyde 3-phosphate dehydrogenase (Gap-C). PCR-amplified segments were analysed for allelic variation using SSCPs, and intrapopulational nucleotide polymorphisms were identified in both L. bradshawii and L. cookii. In the 211bp segment of Gap-C analysed, five nucleotide sites were segregating within populations of L. bradshawii and two in L. cookii.

Variants in the VCAM1 gene and risk for symptomatic stroke in sickle cell disease

Blood ◽  
2002 ◽  
Vol 100 (13) ◽  
pp. 4303-4309 ◽  
Author(s):  
James G. Taylor VI ◽  
Delia C. Tang ◽  
Sharon A. Savage ◽  
Susan F. Leitman ◽  
Seth I. Heller ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Critical Role ◽  
Genome Project ◽  
Monogenic Disease ◽  
Candidate Snps ◽  
Healthy Population ◽  
Nucleotide Polymorphisms ◽  
Coding Region ◽  
A Cell ◽  
The Human Genome Project

Stroke is a major cause of morbidity and mortality in sickle cell (SS) disease. Genetic risk factors have been postulated to contribute to this clinical outcome. The human genome project has substantially increased the catalog of variations in genes, many of which could modify the risk for manifestations of disease outcome in a monogenic disease, namely SS. VCAM1 is a cell adhesion molecule postulated to play a critical role in the pathogenesis of SS disease. We identified a total of 33 single nucleotide polymorphisms (SNPs) by sequencing the entire coding region, 2134 bp upstream of the 5′ end of the published cDNA, 217 bp downstream of the 3′ end of the cDNA, and selected intronic regions of the VCAM1 locus. Allelic frequencies for selected SNPs were determined in a healthy population. We subsequently analyzed 4 nonsynonymous coding, 2 synonymous coding, and 4 common promoter SNPs in a genetic association study of clinically apparent stroke in SS disease conducted in a cohort derived from a single institution in Jamaica (51 symptomatic cases and 51 matched controls). Of the 10 candidate SNPs analyzed in this pilot study, the variant allele of the nonsynonymous SNP, VCAM1 G1238C, may be associated with protection from stroke (odds ratio [OR] 0.35, 95% confidence interval [CI] 0.15-0.83, P = .04). Further study is required to confirm the importance of this variant inVCAM1 as a clinically useful modifier of outcome in SS disease.

scholarly journals Screening of Three Different Alleles of mtDNA (G709A, G3496T, A3537G) in Subpopulation of UKM Students

2018 ◽  
Vol 5 (1) ◽  
pp. 37-40
Author(s):  
Seri Mirianti Ishar ◽  
Jeyaganesan Pillay a/l Balaraman ◽  
Muhammad Jefri Mohd Yusof ◽  
Khairul Osman ◽  
Lee Loong Chuen
Keyword(s):  
Uv Light ◽  
Forensic Genetics ◽  
Nucleotide Polymorphisms ◽  
Coding Region ◽  
Documentation System ◽  
Single Nucleotide ◽  
National University ◽  
Pcr Products ◽  
Malay Population ◽  
Mutation Allele

Human DNA consists of nucleus DNA (nDNA) and mitochondrial DNA (mtDNA). Both are valuable in medicine and forensic genetics but in this project, single nucleotide polymorphisms (SNPs) in mtDNA are used to trace the mutation occurred. Mutations in the sequence of alleles can lead to haplogroup variation and also certain diseases. The purpose of this study is to screen of mutations on alleles G709A, G3496T, and A3537G in Malay population of The National University of Malaysia (UKM) students. These SNPs lie in the ND1 (nitrogen dehydrogenase subunit 1) coding region, and the reports state that these three alleles are prone to mutate. From MitoMap Web site, the mutations of these alleles are reported to have potential in causing several diseases with the collaboration of other SNPs mutation. Allele G709A is reported to have an association with hearing loss and Leber Hereditary Optic Neuropathy (LHON) while allele G3496T is associated to LHON only. Allele A3537G is related to diabetes. A total of 100 DNA samples were collected from Malay students of UKM and preserved on FTA card to be purified later. The concentration of the DNA on the purified FTA card was between 10μM to 20μM. An attempt was made by amplifying those three loci from the genomic DNA. The amplified product was detected and separated using 1% gel electrophoresis. Before sequencing, the PCR products were visualized under UV light using gel documentation system. All PCR products were sequenced to detect the mutation on every single position chosen. From the alignment of sequencing results, allele G709A and allele G3496T showed no mutation. Meanwhile four samples from alleles A3537G has the mutation. From the results obtained, it seems that mutations are rare in all selected alleles. It is recommended to increase the sample size and alleles selected in the future to increase the strength of the study. This study also should be applied to other populations in Malaysia such as Chinese and Indian.  

scholarly journals Variations in MHC class I antigen presentation and immunopeptidome selection pathways

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 1177
Author(s):  
Anita J. Zaitouna ◽  
Amanpreet Kaur ◽  
Malini Raghavan
Keyword(s):  
Cell Surface ◽  
Antigen Presentation ◽  
Surface Expression ◽  
Structural Features ◽  
Class I ◽  
Cell Surface Expression ◽  
Immune Recognition ◽  
Antigen Receptors ◽  
Class I Mhc ◽  
Mhc I

Major histocompatibility class I (MHC-I) proteins mediate immunosurveillance against pathogens and cancers by presenting antigenic or mutated peptides to antigen receptors of CD8+ T cells and by engaging receptors of natural killer (NK) cells. In humans, MHC-I molecules are highly polymorphic. MHC-I variations permit the display of thousands of distinct peptides at the cell surface. Recent mass spectrometric studies have revealed unique and shared characteristics of the peptidomes of individual MHC-I variants. The cell surface expression of MHC-I–peptide complexes requires the functions of many intracellular assembly factors, including the transporter associated with antigen presentation (TAP), tapasin, calreticulin, ERp57, TAP-binding protein related (TAPBPR), endoplasmic reticulum aminopeptidases (ERAPs), and the proteasomes. Recent studies provide important insights into the structural features of these factors that govern MHC-I assembly as well as the mechanisms underlying peptide exchange. Conformational sensing of MHC-I molecules mediates the quality control of intracellular MHC-I assembly and contributes to immune recognition by CD8 at the cell surface. Recent studies also show that several MHC-I variants can follow unconventional assembly routes to the cell surface, conferring selective immune advantages that can be exploited for immunotherapy.

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