scholarly journals Abundant Small Genetic Alterations after Upland Cotton Domestication

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Ying Bao ◽  
Xia Zhang ◽  
Xin Xu
Keyword(s):  
Upland Cotton ◽  
Genetic Alterations ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Genetic Changes ◽  
Noncoding Regions ◽  
Insertion And Deletion ◽  
Short Period ◽  
Wild Cotton ◽  
Reading Frames

Domestication has long been recognized as the most direct and effective way to intentionally influence morphological and physiological phenotypes in plants and animals. Consequently, understanding how small genetic alterations contribute to domestication is of considerable importance. In this study, we resequenced the genome of the wild upland cotton variety Gossypium hirsutum var. yucatanense, the putative wild ancestor of cultivated upland cotton, and then compared single nucleotide polymorphism (SNP) and short insertion and deletion (InDel) variations of the genome with the cultivated accession (TM-1) of G. hirsutum. We found approximately 6.6 million SNPs and 0.7 million InDels between the two genomes. Most of the small genetic variations were anchored in the noncoding regions. With regard to potential coding genes, we found 24,035 genes with nonsynonymous SNPs. Interestingly, 2603 genes in domesticated cotton are found that have changed the positions of stop codons or shifted reading frames from that in G. hirsutum var. yucatanense. This suggests that domestication may have been selected for mutations that restored gene function or that wild cotton has undergone a number of gene inactivation events since its divergence from cultivated cotton. The former scenario seems most likely due to the intense selective pressure applied during the domestication process. These results demonstrate that, within a relatively short period of time, the cotton genome has been readjusted through small genetic changes. The current study provides useful clues for seeking interesting genes for cotton improvement.

Single Nucleotide Polymorphism Array Analysis Of Bone Marrow Failure Patients Reveals Characteristic Patterns Of Genetic Changes

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3710-3710
Author(s):  
Daria V. Babushok ◽  
Hongbo M. Xie ◽  
Jacquelyn J. Roth ◽  
Nieves Perdigones ◽  
Timothy S. Olson ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Single Nucleotide Polymorphism ◽  
Copy Number ◽  
Clinical Utility ◽  
Bone Marrow Failure ◽  
Clonal Evolution ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Genetic Changes ◽  
Conventional Cytogenetics

Abstract Bone marrow failure syndromes (BMFS) are a diverse group of rare life-threatening blood disorders characterized by inadequate hematopoiesis, clonal evolution, and increased risk of hematologic malignancies. Despite recent advances in the understanding of the molecular pathogenesis of BMFS, the ability to diagnose, risk-stratify, and treat patients with these rare disorders remains limited. In both the acquired and the inherited BMFS, the major contributors to mortality are complications of progressive cytopenias, and, albeit to a lesser extent—transformation to myelodysplastic syndrome (MDS) and acute myeloid leukemia. The main predictor of malignant transformation is acquisition of clonal cytogenetic abnormalities. Recently, single nucleotide polymorphism arrays (SNP-A) were proposed as a promising tool for high resolution cytogenetic analysis and surveillance of early clonal changes in BMFS, however, their clinical utility still remains to be established. In 2009, the Comprehensive Bone Marrow Failure Center at the Children’s Hospital of Philadelphia and the Hospital of the University of Pennsylvania incorporated high-density SNP-A as an adjunct to conventional cytogenetics in evaluation of BMFS patients. Here we present a comprehensive analysis of genetic changes in BMFS using 124 SNP-A from 91 patients, who were referred for evaluation of bone marrow failure. SNP-A genotyping was correlated with medical histories, hematopathology, cytogenetic, and molecular data. To assess the potential role of SNP-A in screening for early clonal evolution, longitudinal analysis of SNP-A was performed in 25 patients. We found that acquired copy number-neutral loss of heterozygosity (CN-LOH) was significantly more frequent in acquired aplastic anemia (aAA) than in other BMFS (OR 12.240, 95% CI 1.333-573.696, p<0.01). In contrast, acquired copy number alterations (CNAs) were more typical of MDS and unclassified BMFS. Extended tracts of homozygosity were common, frequently unmasking recessive loci in cases of inherited BMFS. Copy number variants (CNVs) were frequently polymorphic, and we identified several CNVs that are enriched in patients with aAA and neutropenia and may serve as disease modifiers. Clinical utilization analysis revealed that SNP-A can be helpful as an adjunct to conventional cytogenetics at the time of initial diagnosis (e.g. to identify regions of acquired CN-LOH and inherited homozygosity, acquired CNAs with a small clone size, and CNVs). Our longitudinal analysis showed that the likelihood of detecting a new acquired abnormality in a follow-up SNP-A was significantly higher in the setting of relapse than in the setting of stable disease (OR 27, 95% CI 1.23 to 808.54, p=0.035). Our results suggest that acquired CN-LOH is a general phenomenon in aAA, likely mechanistically and prognostically distinct from typical CN-LOH of myeloid malignancies. Our analysis of clinical utility of SNP-A shows the highest yield of detecting new clonal hematopoiesis at diagnosis and at relapse. Disclosures: No relevant conflicts of interest to declare.

The role of a single nucleotide polymorphism of MDM2 in glioblastoma multiforme

2008 ◽  
Vol 109 (5) ◽  
pp. 842-848 ◽  
Author(s):  
Rina G. Khatri ◽  
Kapila Navaratne ◽  
Robert J. Weil
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Glioblastoma Multiforme ◽  
Age Of Onset ◽  
Polymerase Chain Reaction Analysis ◽  
Genetic Alterations ◽  
Primary Brain Tumor ◽  
Healthy Controls ◽  
Wild Type ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide

Object Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults, with a 5-year survival rate of < 5%. Aberrant function of TP53 is common in GBM. Although mutational inactivation of p53 is found in many cases, there remain tumors in which genetic alterations of p53 are absent. Negative regulators of the TP53 pathway such as MDM2, which directly inhibits TP53 expression and activity, may influence the pathogenesis of GBM. To understand its potential function in gliomagenesis, the authors analyzed a novel single nucleotide polymorphism (SNP) in the MDM2 promoter that enhances MDM2 expression. Methods The investigators isolated DNA from 98 patients with GBM and 102 healthy, cancer-free controls. A polymerase chain reaction analysis was performed to determine the MDM2 SNP309 genotype by using distinct primer pairs for the wild-type (T) and mutant (G) alleles. Results The frequency of the mutant MDM2 polymorphism was found to be higher (p = 0.0092) in patients with GBM (54.6%) compared with healthy controls (41.2%); the TT and GG genotypes were more common in healthy controls and patients with GBM (p = 0.0004 and p = 0.02, respectively). Although there was no association between the MDM2 SNP309 and overall survival, the GG genotype was associated with development of GBM at a younger age in patients with tumors harboring wild-type p53, which may mitigate the effect of the MDM2 SNP. Conclusions Although the MDM2 SNP309 does not portend decreased survival, the increased incidence of the mutant G allele in patients with GBM and its influence on age of onset suggest a potential role in the molecular pathogenesis of GBM, and may be a therapeutic target.

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 Neuroblastoma with flat genomic profile: a question of representativity?

2018 ◽  
pp. bcr-2018-225568
Author(s):  
Anders Valind ◽  
Ingrid Öra ◽  
Fredrik Mertens ◽  
David Gisselsson
Keyword(s):  
Single Nucleotide Polymorphism Array ◽  
Reference Sample ◽  
Genetic Alterations ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide Variants ◽  
Array Analysis ◽  
Allelic Profile ◽  
Single Nucleotide ◽  
Whole Exome ◽  
Genome Copy Number

Neuroblastoma is one of the most common paediatric malignancies. Detection of somatic genetic alterations in this tumour is instrumental for its risk stratification and treatment. On the other hand, an absence of detected chromosomal imbalances in neuroblastoma biopsies is difficult to interpret because it is unclear whether this situation truly reflects the tumour genome or if it is due to suboptimal sampling. We here present a neuroblastoma in the left adrenal of a newborn. The tumour was subjected to single-nucleotide polymorphism array analysis of five tumour regions with >80% tumour cells in histological mirror sections. This revealed no aberrations compared with a normal reference sample from the patient. Whole exome sequencing identified two single-nucleotide variants present in most tumour regions, corroborating that the tumour resulted from monoclonal expansion. Our data provide proof-of-principle that rare cases of neuroblastoma can have a normal whole genome copy number and allelic profile.

Dissecting Clonal Diversity in Complex Leukemia Samples with Next Generation Single Nucleotide Polymorphism (SNP)-Copy Number Arrays,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3550-3550
Author(s):  
Sanidad A Marc ◽  
Marilyn L Slovak ◽  
Philip N Mowry ◽  
Joey C Kelly ◽  
Daniel M Jones
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Copy Number ◽  
Dna Microarrays ◽  
De Novo ◽  
Clonal Diversity ◽  
Genetic Alterations ◽  
Next Generation ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Oligonucleotide Arrays

Abstract Abstract 3550 Introduction: The genetic loci altered in many de novo leukemia cases are relatively well-understood and can be accurately assessed by current cytogenetic techniques including multi-probe fluorescence in situ hybridization (FISH). However, identifying the cancer genes involved in complex leukemia karyotypes remains problematic due to the presence of multiple secondary structural rearrangements observed in subclonal populations. These alterations often affect both chromosome (chr) homologues and predominantly involve chr 1, 3, 5, 7, 12 and 17. Such clonal diversity within a tumor reflects the underlying biologically-selected sequential and multiple rearrangements and can, if carefully mapped, highlight the locations of tumor suppressor genes and modifiers involved in disease progression. Previous generations of DNA microarrays have proven useful in dissecting genomic changes in the predominant tumor clone, including copy-neutral loss of heterozygosity (CN-LOH) when single nucleotide polymorphism (SNP) arrays are used. However, a well-known shortcoming of DNA microarrays to date has been their limited sensitivity for accurately detecting low level mosaicism (<20%) and subclonal changes that are common in complex karyotypes. Methods: Using leukemia cases that showed complex karyotypes with up to 4 subclones, we compared the ability of standard (SNP 6.0, Affymetrix) and next-generation (Cytoscan HD, Affymetrix) SNP/copy number oligonucleotide arrays to accurately detect the observed karyotypic subclones and more precisely delineate areas of complex chromosomal alterations. Genomic DNA extracted from fresh material or 24∼48 hour short-term cultures from 8 patients with either de novo or previously treated chronic lymphocytic leukemia (CLL) was assessed on the SNP 6.0 and Cytoscan HD platforms and then compared with their karyotype, and/or supporting FISH studies. Copy number alterations and CN-LOH calls were made using ChAS software (Affymetrix), with the degree of clonal mosaicism analyzed for segmental increments of each chromosome by averaging the smooth signal data. Results and Conclusion: For all 53 CN-LOH and copy number calls, the two arrays gave identical detection rates and similar alteration boundaries in 34 instances (64.1% concordance). The genetic alterations that differed among the cytogenetically-related clones (subclones) were subclonal, in all but 3 instances, and most frequently involved chr 1 and 5. In general, the Cytoscan HD arrays were able to accurately detect karyotypically-confirmed subclones down to the 20% level (as well as distinguishing 90% vs. 100% calls), as opposed to the 30–50% level seen with the SNP 6.0 arrays. Improved detection of the discrete subclones or lower level clonality was attributed to more precise allele peak heights that did not require smoothing. Next-generation SNP/copy number oligonucleotide arrays show great promise in providing additive value to leukemic genomic profiling by clear visual separation of multiple genomic alterations within clonally diverse samples with the potential of identifying novel genetic alterations that may be important in disease progression. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Genetic Analysis of Clinical VZV Isolates Collected in China Reveals a More Homologous Profile

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Longfeng Jiang ◽  
Lin Gan ◽  
Jason Chen ◽  
Mingli Wang
Keyword(s):  
Phylogenetic Analysis ◽  
Open Reading Frames ◽  
Polymorphic Markers ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Varicella Zoster ◽  
Clade B ◽  
The Us ◽  
The World ◽  
Reading Frames

Forty-four varicella-zoster virus (VZV) isolates from China were genotyped by using a scattered single nucleotide polymorphism (SNP) method, including open reading frames (ORFs) 1, 22, 31, 37, 60, 62, 67, and 68. Based on the analysis of the polymorphic markers in the 8 ORFs, all of the 44 isolates can be placed in genotype J defined by the SNP profiles in ORF22 or clade B defined by the SNP profiles in ORFs 31, 37, 60, 62, 67, and 68. The three consecutive nucleotide (CGG) in-frame insertions in ORF 1 were found in 8 (18.2%) isolates, which has not been described in VZV strains from any other part of the world. A novel synonymous A>G substitution in ORF60 was revealed in 4 (9.1%) of the isolates. In addition, a previously described three consecutive nucleotide (ATC) insertion in ORF 60 was found in all the Chinese isolates but not in the US isolate MLS. The results showed all the 44 strains that belong to genotype J/clade B with significantly high homogeneity, and phylogenetic analysis suggested that the 44 Chinese isolates consist of 4 clusters, but interstrain variations also exist. Overall, VZV isolates obtained in China showed significantly higher genetic homogeneity than isolates reported from other countries.

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