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Journal articles on the topic 'OLIGONUCLEOTIDE FREQUENCIES'

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Published: 11 September 2023

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1

Martindale, Colin, and Andrzej K. Konopka. "Oligonucleotide frequencies in DNA follow a Yule distribution." Computers & Chemistry 20, no. 1 (March 1996): 35–38. http://dx.doi.org/10.1016/s0097-8485(96)80005-2.

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2

Wang, G., D. D. Levy, M. M. Seidman, and P. M. Glazer. "Targeted mutagenesis in mammalian cells mediated by intracellular triple helix formation." Molecular and Cellular Biology 15, no. 3 (March 1995): 1759–68. http://dx.doi.org/10.1128/mcb.15.3.1759.

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As an alternative to standard gene transfer techniques for genetic manipulation, we have investigated the use of triple helix-forming oligonucleotides to target mutations to selected genes within mammalian cells. By treating monkey COS cells with oligonucleotides linked to psoralen, we have generated targeted mutations in a simian virus 40 (SV40) vector contained within the cells via intracellular triple helix formation. Oligonucleotide entry into the cells and sequence-specific triplex formation within the SV40 DNA deliver the psoralen to the targeted site. Photoactivation of the psoralen by long-wavelength UV light yields adducts and thereby mutations at that site. We engineered into the SV40 vector novel supF mutation reporter genes containing modified polypurine sites amenable to triplex formation. By comparing the abilities of a series of oligonucleotides to target these new sites, we show that targeted mutagenesis in vivo depends on the strength and specificity of the third-strand binding. Oligonucleotides with weak target site binding affinity or with only partial target site homology were ineffective at inducing mutations in the SV40 vectors within the COS cells. We also show that the targeted mutagenesis is dependent on the oligonucleotide concentration and is influenced by the timing of the oligonucleotide treatment and of the UV irradiation of the cells. Frequencies of intracellular targeted mutagenesis in the range of 1 to 2% were observed, depending upon the conditions of the experiment. DNA sequence analysis revealed that most of the mutations were T.A-to-A.T transversions precisely at the targeted psoralen intercalation site. Several deletions encompassing that site were also seen. The ability to target mutations to selected sites within mammalian cells by using modified triplex-forming oligonucleotides may provide a new research tool and may eventually lead to therapeutic applications.
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3

Hong, Juan. "Prediction of oligonucleotide frequencies based upon dinucleotide frequencies obtained from the nearest neighbor analysis." Nucleic Acids Research 18, no. 6 (1990): 1625–28. http://dx.doi.org/10.1093/nar/18.6.1625.

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4

Tyagi, Antariksh, Sumit K. Bag, Virendra Shukla, Sribash Roy, and Rakesh Tuli. "Oligonucleotide Frequencies of Barcoding Loci Can Discriminate Species across Kingdoms." PLoS ONE 5, no. 8 (August 20, 2010): e12330. http://dx.doi.org/10.1371/journal.pone.0012330.

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5

Goussarov, Gleb, Ilse Cleenwerck, Mohamed Mysara, Natalie Leys, Pieter Monsieurs, Guillaume Tahon, Aurélien Carlier, Peter Vandamme, and Rob Van Houdt. "PaSiT: a novel approach based on short-oligonucleotide frequencies for efficient bacterial identification and typing." Bioinformatics 36, no. 8 (January 3, 2020): 2337–44. http://dx.doi.org/10.1093/bioinformatics/btz964.

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Abstract Motivation One of the most widespread methods used in taxonomy studies to distinguish between strains or taxa is the calculation of average nucleotide identity. It requires a computationally expensive alignment step and is therefore not suitable for large-scale comparisons. Short oligonucleotide-based methods do offer a faster alternative but at the expense of accuracy. Here, we aim to address this shortcoming by providing a software that implements a novel method based on short-oligonucleotide frequencies to compute inter-genomic distances. Results Our tetranucleotide and hexanucleotide implementations, which were optimized based on a taxonomically well-defined set of over 200 newly sequenced bacterial genomes, are as accurate as the short oligonucleotide-based method TETRA and average nucleotide identity, for identifying bacterial species and strains, respectively. Moreover, the lightweight nature of this method makes it applicable for large-scale analyses. Availability and implementation The method introduced here was implemented, together with other existing methods, in a dependency-free software written in C, GenDisCal, available as source code from https://github.com/LM-UGent/GenDisCal. The software supports multithreading and has been tested on Windows and Linux (CentOS). In addition, a Java-based graphical user interface that acts as a wrapper for the software is also available. Supplementary information Supplementary data are available at Bioinformatics online.
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6

McFarland, JG, RH Aster, JB Bussel, JG Gianopoulos, RS Derbes, and PJ Newman. "Prenatal diagnosis of neonatal alloimmune thrombocytopenia using allele- specific oligonucleotide probes." Blood 78, no. 9 (November 1, 1991): 2276–82. http://dx.doi.org/10.1182/blood.v78.9.2276.2276.

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Abstract The prediction of neonatal alloimmune thrombocytopenia (NATP) in affected families has, in the past, been based on information about gene frequencies of the antigen systems involved, parental phenotyping, and fetal platelet counts. We explored the feasibility of allele- specific oligonucleotide probe typing for PIA antigens to determine the risk of second or subsequent fetuses in families where one infant had a diagnosis of anti-PIA1-mediated NATP. A total of eight families at risk for delivering an affected fetus were studied with both serologic and oligonucleotide typing. The correlation between serologic and oligonucleotide PIA types was 100%. Similarly, in an additional eight families not at risk for PIA1-mediated NATP, serologic and oligonucleotide typing maintained a perfect correlation. DNA isolated from fetal leukocytes as well as fetal amniocytes was successfully typed using this technology. Oligonucleotide-based typing of fetuses at risk for NATP whose fathers are heterozygous for the PIA antigens allows early recognition of affected fetuses so that prenatal therapy of mothers can be instituted if necessary. When fetuses are found to be unaffected, invasive, and/or expensive, prenatal interventions can be avoided.
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7

McFarland, JG, RH Aster, JB Bussel, JG Gianopoulos, RS Derbes, and PJ Newman. "Prenatal diagnosis of neonatal alloimmune thrombocytopenia using allele- specific oligonucleotide probes." Blood 78, no. 9 (November 1, 1991): 2276–82. http://dx.doi.org/10.1182/blood.v78.9.2276.bloodjournal7892276.

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The prediction of neonatal alloimmune thrombocytopenia (NATP) in affected families has, in the past, been based on information about gene frequencies of the antigen systems involved, parental phenotyping, and fetal platelet counts. We explored the feasibility of allele- specific oligonucleotide probe typing for PIA antigens to determine the risk of second or subsequent fetuses in families where one infant had a diagnosis of anti-PIA1-mediated NATP. A total of eight families at risk for delivering an affected fetus were studied with both serologic and oligonucleotide typing. The correlation between serologic and oligonucleotide PIA types was 100%. Similarly, in an additional eight families not at risk for PIA1-mediated NATP, serologic and oligonucleotide typing maintained a perfect correlation. DNA isolated from fetal leukocytes as well as fetal amniocytes was successfully typed using this technology. Oligonucleotide-based typing of fetuses at risk for NATP whose fathers are heterozygous for the PIA antigens allows early recognition of affected fetuses so that prenatal therapy of mothers can be instituted if necessary. When fetuses are found to be unaffected, invasive, and/or expensive, prenatal interventions can be avoided.
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8

Obata, Fumiya, Koichi Ito, Takehisa Kaneko, Yong-guang Yang, Kelji Onda, Ichiro Ito, Noriko Yabe, Koji Watanabo, and Noboru Kashiwagi. "HLA-DR gene frequencies in the Japanese population obtained by oligonucleotide genotyping." Tissue Antigens 38, no. 1 (July 1991): 124–32. http://dx.doi.org/10.1111/j.1399-0039.1991.tb02025.x.

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9

Abe, Takashi, Yuta Hamano, and Toshimichi Ikemura. "Visualization of Genome Signatures of Eukaryote Genomes by Batch-Learning Self-Organizing Map with a Special Emphasis onDrosophilaGenomes." BioMed Research International 2014 (2014): 1–8. http://dx.doi.org/10.1155/2014/985706.

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A strategy of evolutionary studies that can compare vast numbers of genome sequences is becoming increasingly important with the remarkable progress of high-throughput DNA sequencing methods. We previously established a sequence alignment-free clustering method “BLSOM” for di-, tri-, and tetranucleotide compositions in genome sequences, which can characterize sequence characteristics (genome signatures) of a wide range of species. In the present study, we generated BLSOMs for tetra- and pentanucleotide compositions in approximately one million sequence fragments derived from 101 eukaryotes, for which almost complete genome sequences were available. BLSOM recognized phylotype-specific characteristics (e.g., key combinations of oligonucleotide frequencies) in the genome sequences, permitting phylotype-specific clustering of the sequences without any information regarding the species. In our detailed examination of 12Drosophilaspecies, the correlation between their phylogenetic classification and the classification on the BLSOMs was observed to visualize oligonucleotides diagnostic for species-specific clustering.
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10

Bai, Yu, Yuki Iwasaki, Shigehiko Kanaya, Yue Zhao, and Toshimichi Ikemura. "A Novel Bioinformatics Method for Efficient Knowledge Discovery by BLSOM from Big Genomic Sequence Data." BioMed Research International 2014 (2014): 1–11. http://dx.doi.org/10.1155/2014/765648.

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With remarkable increase of genomic sequence data of a wide range of species, novel tools are needed for comprehensive analyses of the big sequence data. Self-Organizing Map (SOM) is an effective tool for clustering and visualizing high-dimensional data such as oligonucleotide composition on one map. By modifying the conventional SOM, we have previously developed Batch-Learning SOM (BLSOM), which allows classification of sequence fragments according to species, solely depending on the oligonucleotide composition. In the present study, we introduce the oligonucleotide BLSOM used for characterization of vertebrate genome sequences. We first analyzed pentanucleotide compositions in 100 kb sequences derived from a wide range of vertebrate genomes and then the compositions in the human and mouse genomes in order to investigate an efficient method for detecting differences between the closely related genomes. BLSOM can recognize the species-specific key combination of oligonucleotide frequencies in each genome, which is called a “genome signature,” and the specific regions specifically enriched in transcription-factor-binding sequences. Because the classification and visualization power is very high, BLSOM is an efficient powerful tool for extracting a wide range of information from massive amounts of genomic sequences (i.e., big sequence data).
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11

Liu, Shaolin, Nicholas A. Tinker, and Diane E. Mather. "Exact word matches in rice pseudomolecules." Genome 49, no. 8 (August 1, 2006): 1047–51. http://dx.doi.org/10.1139/g06-055.

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Using pseudomolecules of assembled genomic sequence, we computed the frequencies of 6 to 24 bp oligonucleotide (oligo) "words" across the genome of rice (Oryza sativa L. subsp. japonica). All oligos of 10 or fewer basepairs were repeated at least 12 times in the genome. The percentage of unique (non-repeated) oligos ranged from 0.1% for 12 bp oligos to 76.0% for 24 bp oligos. For three 200 kb regions, we annotated each nucleotide position with the genome-wide frequency of the 18 bp oligo starting at that position. These frequencies formed landscapes consisting of high- and low-frequency zones. Low-frequency zones contained occasional high-frequency spikes; these may represent footprints of RIM2 transposon activity. BLASTn searches of high-frequency non-SSR (simple sequence repeat) 18 bp oligos returned few sequences from species other than rice. These results demonstrate that, in rice, words are not randomly used between different regions within the same genome, and indicate that words that are frequently repeated within the rice genome tend to be unique to rice.Key words: oligonucleotide, sequence repetition, word match frequency, rice.
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12

Chan, Chon-Kit Kenneth, Arthur L. Hsu, Sen-Lin Tang, and Saman K. Halgamuge. "Using Growing Self-Organising Maps to Improve the Binning Process in Environmental Whole-Genome Shotgun Sequencing." Journal of Biomedicine and Biotechnology 2008 (2008): 1–10. http://dx.doi.org/10.1155/2008/513701.

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Metagenomic projects using whole-genome shotgun (WGS) sequencing produces many unassembled DNA sequences and small contigs. The step of clustering these sequences, based on biological and molecular features, is called binning. A reported strategy for binning that combines oligonucleotide frequency and self-organising maps (SOM) shows high potential. We improve this strategy by identifying suitable training features, implementing a better clustering algorithm, and defining quantitative measures for assessing results. We investigated the suitability of each of di-, tri-, tetra-, and pentanucleotide frequencies. The results show that dinucleotide frequency is not a sufficiently strong signature for binning 10 kb long DNA sequences, compared to the other three. Furthermore, we observed that increased order of oligonucleotide frequency may deteriorate the assignment result in some cases, which indicates the possible existence of optimal species-specific oligonucleotide frequency. We replaced SOM with growing self-organising map (GSOM) where comparable results are obtained while gaining7%–15%speed improvement.
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13

Harvey, D., J. J. Pointon, C. Sleator, A. Meenagh, C. Farrar, J. Y. Sun, D. Senitzer, D. Middleton, M. A. Brown, and B. P. Wordsworth. "Analysis of killer immunoglobulin-like receptor genes in ankylosing spondylitis." Annals of the Rheumatic Diseases 68, no. 4 (November 19, 2008): 595–98. http://dx.doi.org/10.1136/ard.2008.095927.

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Objectives:To assess the possible association of killer immunoglobulin-like receptor (KIR) genes, specifically KIR3DL1, KIR3DS1 and KIR3DL2, with ankylosing spondylitis (AS).Methods:14 KIR genes were genotyped in 200 UK patients with AS and 405 healthy controls using multiplex polymerase chain reaction. Sequence-specific oligonucleotide probes were used to subtype 368 cases with AS and 366 controls for 12 KIR3DL2 alleles. Differences in KIR genotypes and KIR3DL2 allele frequencies were assessed using the χ2 test.Results:KIR3DL1 and KIR3DS1 gene frequencies were very similar in cases with AS and controls (odds ratio = 1.5, 95% confidence interval 0.8 to 3.0, and odds ratio = 1.02, 95% confidence interval 0.2 to 5.3, respectively). KIR3DL2 allele frequencies were not significantly different between cases with AS and controls.Conclusions:Neither the KIR gene content of particular KIR haplotypes nor KIR3DL2 polymorphisms contribute to AS.
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Armstrong, EG, and JTP Verhoeven. "Machine learning analyses of bacterial oligonucleotide frequencies to assess the benthic impact of aquaculture." Aquaculture Environment Interactions 12 (April 9, 2020): 131–37. http://dx.doi.org/10.3354/aei00353.

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Aquaculture is a rapidly expanding industry and is now one of the primary sources of all consumed seafood. Intensive aquaculture production is associated with organic enrichment, which occurs as organic material settles onto the seafloor, creating anoxic conditions which disrupt ecological processes. Bacteria are sensitive bioindicators of organic enrichment, and supervised classifiers using features derived from 16s rRNA gene sequences have shown potential to become useful in aquaculture environmental monitoring. Current taxonomy-based approaches, however, are time intensive and built upon emergent features which cannot easily be condensed into a monitoring pipeline. Here, we used a taxonomy-free approach to examine 16s rRNA gene sequences derived from flocculent matter underneath and in proximity to hard-bottom salmon aquaculture sites in Newfoundland, Canada. Tetranucleotide frequencies (k = 4) were tabulated from sample sequences and included as features in a machine learning pipeline using the random forest algorithm to predict 4 levels of benthic disturbance; resulting classifications were compared to those obtained using a published taxonomy-based approach. Our results show that k-mer count features can effectively be used to create highly accurate predictions of benthic disturbance and can resolve intermediate changes in seafloor condition. In addition, we present a robust assessment of model performance which accounts for the effect of randomness in model creation. This work outlines a flexible framework for environmental assessments at aquaculture sites that is highly reproducible and free of taxonomy-assignment bias.
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Liu, Haipeng, and Darrell Irvine. "Immunostimulatory properties of dynamic oligonucleotide micelles (53.9)." Journal of Immunology 188, no. 1_Supplement (May 1, 2012): 53.9. http://dx.doi.org/10.4049/jimmunol.188.supp.53.9.

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Abstract Synthetic immunostimulatory oligonucleotides such as double-stranded RNA or unmethylated cytosine-guanosine motifs (CpG-ODNs) mimic molecular signatures of pathogens and trigger an immunostimulatory cascade; as a result, these synthetic ODNs have been extensively studied as therapeutic agents for cancer and as vaccine adjuvants. Using a self-assembly approach, we designed lipo-CpG-ODN molecules composed of CpG oligos conjugated with diacyl lipid tails. These dynamic amphiphiles form compact micelles ~20 nm in diam. in water but can also disassemble and insert their acyl tails into the plasma membrane when incubated with cells. These two key elements of the CpG micelle-ultra-small physical size and cell membrane insertion capability- combine to greatly enhance the adjuvant properties of CpG or other co-associated TLR agonists. Injection of CpG micelles s.c. resulted in a 5-15-fold enhancement of draining lymph node (dLN) retention compared with free CpG or stabilized CpG-micelles incapable of inserting into membranes. Immunization with soluble antigen mixed with CpG micelles induced 10-fold increased frequencies of antigen-specific T-cells in blood and elicited higher antibody production than equivalent doses of soluble CpG, and also elicited stronger responses than CpG-micelles lacking membrane insertion potential. Thus, dynamic micellar TLR agonists may be of interest as novel vaccine adjuvants.
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Keller-Seitz, Monika U., Ulrich Certa, Christian Sengstag, Friedrich E. Würgler, Mingzeng Sun, and Michael Fasullo. "Transcriptional Response of Yeast to Aflatoxin B1: Recombinational Repair InvolvingRAD51andRAD1." Molecular Biology of the Cell 15, no. 9 (September 2004): 4321–36. http://dx.doi.org/10.1091/mbc.e04-05-0375.

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The potent carcinogen aflatoxin B1is a weak mutagen but a strong recombinagen in Saccharomyces cerevisiae. Aflatoxin B1exposure greatly increases frequencies of both heteroallelic recombination and chromosomal translocations. We analyzed the gene expression pattern of diploid cells exposed to aflatoxin B1using high-density oligonucleotide arrays comprising specific probes for all 6218 open reading frames. Among 183 responsive genes, 46 are involved in either DNA repair or in control of cell growth and division. Inducible growth control genes include those in the TOR signaling pathway and SPO12, whereas PKC1 is downregulated. Eleven of the 15 inducible DNA repair genes, including RAD51, participate in recombination. Survival and translocation frequencies are reduced in the rad51 diploid after aflatoxin B1exposure. In mec1 checkpoint mutants, aflatoxin B1exposure does not induce RAD51 expression or increase translocation frequencies; however, when RAD51 is constitutively overexpressed in the mec1 mutant, aflatoxin B1exposure increased translocation frequencies. Thus the transcriptional profile after aflatoxin B1exposure may elucidate the genotoxic properties of aflatoxin B1.
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Bohlin, Jon, Eystein Skjerve, and David W. Ussery. "Reliability and applications of statistical methods based on oligonucleotide frequencies in bacterial and archaeal genomes." BMC Genomics 9, no. 1 (2008): 104. http://dx.doi.org/10.1186/1471-2164-9-104.

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18

Arnau, Vicente, Wladimiro Díaz-Villanueva, Jorge Mifsut Benet, Paula Villasante, Beatriz Beamud, Paula Mompó, Rafael Sanjuan, Fernando González-Candelas, Pilar Domingo-Calap, and Mária Džunková. "Inference of the Life Cycle of Environmental Phages from Genomic Signature Distances to Their Hosts." Viruses 15, no. 5 (May 19, 2023): 1196. http://dx.doi.org/10.3390/v15051196.

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The environmental impact of uncultured phages is shaped by their preferred life cycle (lytic or lysogenic). However, our ability to predict it is very limited. We aimed to discriminate between lytic and lysogenic phages by comparing the similarity of their genomic signatures to those of their hosts, reflecting their co-evolution. We tested two approaches: (1) similarities of tetramer relative frequencies, (2) alignment-free comparisons based on exact k = 14 oligonucleotide matches. First, we explored 5126 reference bacterial host strains and 284 associated phages and found an approximate threshold for distinguishing lysogenic and lytic phages using both oligonucleotide-based methods. The analysis of 6482 plasmids revealed the potential for horizontal gene transfer between different host genera and, in some cases, distant bacterial taxa. Subsequently, we experimentally analyzed combinations of 138 Klebsiella pneumoniae strains and their 41 phages and found that the phages with the largest number of interactions with these strains in the laboratory had the shortest genomic distances to K. pneumoniae. We then applied our methods to 24 single-cells from a hot spring biofilm containing 41 uncultured phage–host pairs, and the results were compatible with the lysogenic life cycle of phages detected in this environment. In conclusion, oligonucleotide-based genome analysis methods can be used for predictions of (1) life cycles of environmental phages, (2) phages with the broadest host range in culture collections, and (3) potential horizontal gene transfer by plasmids.
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Ameen, Reem, Salem H. Al Shemmari, and Steven G. E. Marsh. "HLA Haplotype Frequencies and Genetic Profiles of the Kuwaiti Population." Medical Principles and Practice 29, no. 1 (March 15, 2019): 39–45. http://dx.doi.org/10.1159/000499593.

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Objective: The aim of this study was to assess the HLA haplotype frequencies and genetic profiles of the Kuwaiti population. Materials and Methods: Whole venous blood was obtained from 595 healthy, unrelated Kuwaiti volunteers. The study population was genotyped for HLA class I (HLA-A, HLA-B, and HLA-C) and class II (HLA-DRB1 and HLA-DQB1) loci using sequence-specific oligonucleotide (SSO) probe-based hybridization and high-resolution HLA genotyping. Haplotype frequencies were estimated using an implementation of the expectation maximization algorithm that resolves both phase and allelic ambiguity. The Kuwaiti population was compared with other populations from the US National Marrow Donor Program (NMDP), by running a principal component analysis (PCA) on the relevant haplotype frequencies. Results: The most common HLA class I alleles in Kuwait were HLA-A*02:01g, HLA-C*06:02g, and HLA-B*50:01g with frequencies of 16, 14, and 12%, respectively. The most common HLA class II alleles in Kuwait were HLA-DQB1*02:01g and HLA-DRB1*07:01 with frequencies of 29.7 and 16.5%, respectively. The most common Kuwaiti haplotype observed was HLA-A*02:01g∼HLA-C*06:02g∼HLA-B*50:01g∼HLA-DRB1*07:01∼HLA-DQB1*02:01g at a frequency of 2.3%. The PCA demonstrated close genetic proximity of the Kuwaiti population with Middle Eastern, Southeast Asian, and North African populations in the NMDP. Conclusion: Identifying the haplotype diversity in the Kuwaiti population will contribute to the selection of an HLA-match for HSCT, disease associations, pharmacogenomics, and knowledge of pop­ulation HLA diversity.
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Ikemura, Toshimichi, Yuki Iwasaki, Kennosuke Wada, Yoshiko Wada, and Takashi Abe. "AI-based search for convergently expanding, advantageous mutations in SARS-CoV-2 by focusing on oligonucleotide frequencies." PLOS ONE 17, no. 8 (August 31, 2022): e0273860. http://dx.doi.org/10.1371/journal.pone.0273860.

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Among mutations that occur in SARS-CoV-2, efficient identification of mutations advantageous for viral replication and transmission is important to characterize and defeat this rampant virus. Mutations rapidly expanding frequency in a viral population are candidates for advantageous mutations, but neutral mutations hitchhiking with advantageous mutations are also likely to be included. To distinguish these, we focus on mutations that appear to occur independently in different lineages and expand in frequency in a convergent evolutionary manner. Batch-learning SOM (BLSOM) can separate SARS-CoV-2 genome sequences according by lineage from only providing the oligonucleotide composition. Focusing on remarkably expanding 20-mers, each of which is only represented by one copy in the viral genome, allows us to correlate the expanding 20-mers to mutations. Using visualization functions in BLSOM, we can efficiently identify mutations that have expanded remarkably both in the Omicron lineage, which is phylogenetically distinct from other lineages, and in other lineages. Most of these mutations involved changes in amino acids, but there were a few that did not, such as an intergenic mutation.
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Zhang, Jing, Jun Hu, Xiu-fan Shi, Huai Cao, and Wei-bo Liu. "Detection of potential positive regulatory motifs of transcription in yeast introns by comparative analysis of oligonucleotide frequencies." Computational Biology and Chemistry 27, no. 4-5 (October 2003): 497–506. http://dx.doi.org/10.1016/j.compbiolchem.2003.09.005.

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22

Osman, Awad E., Faviel F. Gonzalez-Galarza, Mohamed Mubasher, Hanan Al-Harthi, Nezar Eltayeb Elsheikh, Noureddine Berka, Derek Middleton, and Gehad Elghazali. "HLA-A, -B, -C, -DRB1, and -DQB1 Allele Lineages and Haplotype Frequencies among Saudis." Immunology and Immunogenetics Insights 6 (January 2014): III.S16769. http://dx.doi.org/10.4137/iii.s16769.

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There are few reported studies on Saudi population for human leukocyte antigens (HLA) genes. We investigated allele lineages (two-digit) and haplotype frequencies of HLA-A, -B, -C, -DRB1, and -DQB1 loci in 499 healthy unrelated individuals, selected from potential bone marrow transplant (BMT) families’ donors at King Fahad Medical City (KFMC), Saudi Arabia (SA). Genotyping was performed by Sequence Specific Oligonucleotide Probe (SSOP) utilizing a Luminex-based method. Allele lineages and haplotype frequencies were evaluated along with principal component analysis (PCA) to compare findings with previously reported data on Arab related populations. A total of 18 allele lineages for HLA-A, 28 for -B, 14 for -C, 13 for -DRB1, and 5 for -DQB1 were detected. High values for linkage disequilibrium indicators were found for B:C ( D’ = 0.86599) and DRB1:DQB1 ( D’ = 0.89468) loci. Additionally, PCA results confirmed previous findings on this population, but also indicated some genetic distances from other Arab related populations. The present study helps in further investigations of this population in anthropological analysis and HLA-associated disease studies.
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23

Mehta, S. C., B. P. Mishra, and M. S. Sahani. "Genetic differentiation of Indian camel (Camelus dromedarius) breeds using random oligonucleotide primers." Animal Genetic Resources Information 39 (April 2006): 77–88. http://dx.doi.org/10.1017/s1014233900002157.

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SummaryThe camel population in India is facing a severe decline which demands that immediate steps are taken to ensure its conservation. Characterisation is an integral part of the conservation program. The Polymerase Chain Reaction-Randomly Amplified Polymorphic DNA profile of unrelated camels of the Bikaneri (29), Jaisalmeri (30) and Kachchhi (18) breeds were analyzed. Reproducible polymorphic bands with varying frequencies among the three breeds of camel were obtained with five oligonucleotide primers. A total of 75 bands were amplified, of which 27 (36%) were polymorphic. The probability of obtaining identical fingerprints was observed to be the lowest in primer GC-10 (5.7%) followed by OP-08 (8.7%), GT-10 (11.3%), G-2 (15.5%) and G-1 (80%). Breed informative bands were amplified. The maximum genetic variability was observed in the Bikaneri (0.80±0.05) followed by the Kachchhi (0.84±0.06) and the Jaisalmeri (0.87±0.05) breeds. The inter-breed genetic distance estimates indicated a closer relationship in the Bikaneri-Kachchhi camels, (0.075), followed by the Jaisalmeri-Kachchhi (0.106) and Bikaneri-Jaisalmeri (0.132) breeds. A similar genetic relationship was observed when the degree of population subdivision was measured between the Bikaneri-Kachchhi (0.529), Jaisalmeri-Kachchhi (0.558) and Bikaneri-Jaisalmeri (0.566) breeds.
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Blake, Jonathan D., and R. D. Blake. "The use of multi-dimensional scaling to investigate similarities between non-random oligonucleotide frequencies in introns and exons." Computers & Chemistry 17, no. 2 (June 1993): 177–84. http://dx.doi.org/10.1016/0097-8485(93)85008-z.

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Mahdi, Rami N., and Eric C. Rouchka. "RBF-TSS: Identification of Transcription Start Site in Human Using Radial Basis Functions Network and Oligonucleotide Positional Frequencies." PLoS ONE 4, no. 3 (March 16, 2009): e4878. http://dx.doi.org/10.1371/journal.pone.0004878.

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26

Wills, Mark R., Andrew J. Carmichael, Michael P. Weekes, Kim Mynard, Georgina Okecha, Ray Hicks, and J. G. Patrick Sissons. "Human Virus-Specific CD8+ CTL Clones Revert from CD45ROhigh to CD45RAhigh In Vivo: CD45RAhighCD8+ T Cells Comprise Both Naive and Memory Cells." Journal of Immunology 162, no. 12 (June 15, 1999): 7080–87. http://dx.doi.org/10.4049/jimmunol.162.12.7080.

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Abstract It has been generally believed that human CD8+ memory cells are principally found within the CD45ROhigh population. There are high frequencies of CD8+ memory CTL specific for the human CMV tegument phosphoprotein pp65 in PBMC of long-term virus carriers; the large population of memory CTL specific for a given pp65 peptide contains individual CTL clones that have greatly expanded. In this study, we found high frequencies of pp65 peptide-specific memory CTL precursors in the CD45ROhighCD45RA− population, but also appreciable frequencies in the CD45RAhigh subpopulation. Because the majority of CD8+ T cells in PBMC are CD45RAhigh, more of the total pp65-specific memory CTL pool is within the CD45RAhigh than in the CD45ROhigh compartment. Using clonotypic oligonucleotide probes to quantify the size of individual pp65-specific CTL clones in vivo, we found the CD45RAhigh population contributed 6- to 10-fold more than the CD45ROhigh population to the total virus-specific clone size in CD8+ cells. During primary CMV infection, an individual virus-specific CTL clone was initially CD45ROhigh, but after resolution of infection this clone was detected in both the CD45ROhigh and the CD45RAhigh populations. We conclude that CD45RA+ human CD8+ T cells do not solely comprise naive cells, but contain a very significant proportion of memory cells, which can revert from the CD45ROhigh to CD45RAhigh phenotype in vivo.
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Huang, Xin, Kushi Kushekhar, Ilja Nolte, Wierd Kooistra, Lydia Visser, Ilby Bouwman, Niels Kouprie, et al. "Multiple HLA class I and II associations in classical Hodgkin lymphoma and EBV status defined subgroups." Blood 118, no. 19 (November 10, 2011): 5211–17. http://dx.doi.org/10.1182/blood-2011-04-342998.

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AbstractThe pathogenesis of classical Hodgkin lymphoma (cHL) involves environmental and genetic factors. To explore the role of the human leukocyte antigen (HLA) genes, we performed a case-control genotyping study in 338 Dutch cHL patients and more than 5000 controls using a PCR-based sequence-specific oligonucleotide probe hybridization approach. HLA-A68 and HLA-DR11 (5) were significantly increased in the cHL patient population compared with the controls. Three class II associations were observed in the EBV− cHL population with an increase of HLA-DR15 (2) and a decrease of HLA-DR4 and HLA-DR7. Allele frequencies of HLA-A1, HLA-B37, and HLA-DR10 were significantly increased in the EBV+ cHL population; these alleles are in strong linkage disequilibrium and form a common haplotype in whites. The allele frequency of HLA-A2 was significantly decreased in the EBV+ cHL population. Sequence-specific oligonucleotide probe analysis revealed significant differences between EBV+ and EBV− cHL patients for 19 probes that discriminate between HLA-A*01 and HLA-A*02. In conclusion, the HLA-A1 and HLA-A2 antigens and not specific single nucleotide variants shared by multiple alleles are responsible for the association with EBV+ cHL. Furthermore, several new protective and predisposing HLA class I and II associations for the EBV+, the EBV−, and the entire cHL population were identified.
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Takahashi, Chikara, Amelia Au-Yeung, Johnny Gutierrez, Shadi Toghi-Eshghi, Rod Mathews, and William O’Gorman. "Evaluation of oligonucleotide conjugated antibodies as reporter molecules in single-cell assays." Journal of Immunology 204, no. 1_Supplement (May 1, 2020): 86.35. http://dx.doi.org/10.4049/jimmunol.204.supp.86.35.

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Abstract Multiplexing in conventional flow and mass cytometric analysis has been constrained by both the number of available reporter molecules as well as signal spillover between these molecules. Monoclonal antibodies(mAbs) conjugated to oligonucleotides have been used in the design of ultrasensitive immunoassays but the multiplexing potential of these reagents have only recently been realized. The Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq) method is established and uses oligo-conjugated mAbs and single-cell RNA sequencing technology to simultaneously enable the quantitation of both mRNA and protein molecules. Using the BD Rhapsody™ platform and BD® AbSeq, we examined the expression of 399 genes and 40 proteins in human PBMCs. The ability of single cell RNA-seq (scRNA-seq) to differentiate major and minor subsets of immune cells was evaluated. As in conventional cytometric analysis, immune cell populations could be identified based on the expression of canonical cell surface proteins and we compared the frequency of immune cell populations identified via scRNA-seq to CyTOF technology. Additionally, genes expected to be up- or down-regulated between established major populations such as T- and B-cells were observed thereby encouraging further analysis of gene expression in minor sub-populations. Overall, immune cell frequencies were found to be highly concordant between technologies. Single-cell “multi-omics” in which mRNA, proteins, and immune cell clonality are simultaneously measured on single cells thus stands poised to innovate drug development by providing unprecedented depth in the analysis of cells expressing therapeutic targets and driving disease pathogenesis.
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29

Zeiny, Sarmad M. "The correlation between HLA class II and β-thalassemia major in Al-Karama teaching hospital." Journal of the Faculty of Medicine Baghdad 58, no. 4 (January 3, 2016): 366–70. http://dx.doi.org/10.32007/jfacmedbagdad.584287.

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Background: Thalassemia is a form of inherited autosomal recessive blood disorder characterized by abnormal formation of hemoglobin.Objective: Determine frequencies & association of HLA class II alleles (DRB1& DQB1) in Iraqi β-thalassemia major patients.Patients: seventy unrelated randomly selected β-thalassemia major patients, and one hundred unrelated randomly selected healthy individuals, composed the control group.Methods: low resolution PCR-SSO (Sequence Specific Oligonucleotide) technique was used for HLA typing.Results: HLA DQB1*5 give significance importance as an etiological risk factor for β-thalassemia major; HLA DQB1*3 give significance importance as a preventive risk factor for β-thalassemia major.Conclusion: The positive association of HLA DQB1*5 and DQB1*3 with β-thalassemia major may have the possibility that these antigens, or the genes encoding them, are closely linked with other possible susceptibility genes.
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30

Doddapaneni, Harsha, Sara Javornik Cregeen, Richard Sucgang, Qingchang Meng, Xiang Qin, Vasanthi Avadhanula, Hsu Chao, et al. "Oligonucleotide capture sequencing of the SARS-CoV-2 genome and subgenomic fragments from COVID-19 individuals." PLOS ONE 16, no. 8 (August 25, 2021): e0244468. http://dx.doi.org/10.1371/journal.pone.0244468.

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The newly emerged and rapidly spreading SARS-CoV-2 causes coronavirus disease 2019 (COVID-19). To facilitate a deeper understanding of the viral biology we developed a capture sequencing methodology to generate SARS-CoV-2 genomic and transcriptome sequences from infected patients. We utilized an oligonucleotide probe-set representing the full-length genome to obtain both genomic and transcriptome (subgenomic open reading frames [ORFs]) sequences from 45 SARS-CoV-2 clinical samples with varying viral titers. For samples with higher viral loads (cycle threshold value under 33, based on the CDC qPCR assay) complete genomes were generated. Analysis of junction reads revealed regions of differential transcriptional activity among samples. Mixed allelic frequencies along the 20kb ORF1ab gene in one sample, suggested the presence of a defective viral RNA species subpopulation maintained in mixture with functional RNA in one sample. The associated workflow is straightforward, and hybridization-based capture offers an effective and scalable approach for sequencing SARS-CoV-2 from patient samples.
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31

Goldberg, A. C., J. M. Chiarella, M. L. C. Marin, C. Rosales, D. Banic, M. A. Oliveira, H. Rodrigues, C. S. Viggiani, and J. Kalil. "Molecular typing of HLA class II antigens in a São Paulo population." Genetics and Molecular Biology 21, no. 3 (September 1998): 301–5. http://dx.doi.org/10.1590/s1415-47571998000300001.

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In the present paper we show data obtained from a normal population with a racially mixed profile typical of the city of São Paulo, State of São Paulo. Data were generated with polymerase chain reaction using sequence specific primers (PCR-SSP) for HLA-DRB and polymerase chain reaction followed by hybridization with sequence specific oligonucleotide probes (PCR-SSO) for HLA-DQA1 and HLA-DQB1 loci. HLA-DRB, DQA1, DQB1 and haplotype frequencies as well as common linkage disequilibria were found. This population was also shown to be in genetic equilibrium according to the Hardy-Weinberg law. HLA-DR typing of a normal sample from the city of Porto Velho, State of Rondonia, highlighted the importance of different sets of HLA profiles found in other regions of the country. This database provides essential information for screening studies of disease associations, forensic analyses and transplants.
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32

Zhang, Siyu, Pei Du, Xueying Lu, Jiaxin Fang, Jiaqi Wang, Xuejun Chen, Jianyong Chen, et al. "Frequent numerical and structural chromosome changes in early generations of synthetic hexaploid wheat." Genome 65, no. 4 (April 2022): 205–17. http://dx.doi.org/10.1139/gen-2021-0074.

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Modern hexaploid wheat (Triticum aestivum L.; AABBDD) has evolved from a hybrid of tetraploid wheat (closely related to Triticum turgidum L. ssp. durum (Desf.) Husn., AABB) and goatgrass (Aegilops tauschii Coss., DD). Variations in chromosome structure and ploidy have played important roles in wheat evolution. How these variations occur and their role in expanding the genetic diversity of modern wheat remain largely unknown. Synthetic hexaploid wheat (SHW) can be used to investigate chromosome variations that occur during the early generations of existence. SHW lines derived by crossing durum wheat ‘Langdon’ with 12 Ae. tauschii accessions were analyzed using oligonucleotide probe multiplex fluorescence in situ hybridization (FISH) of metaphase chromosomes and SNP markers. Cluster analysis based on SNP markers categorizes them into three groups. Among 702 plants from the S8 and S9 generations, 415 (59.12%) carried chromosome variations involving all 21 chromosomes, but with different frequencies for each chromosome and sub-genome. Total chromosome variation frequencies varied between lines, but there was no significant difference among the three groups. The non-random chromosome variations in the SHW lines detected in this study may indicate that similar variations occurred in the early stages of wheat polyploidization and played important roles in wheat evolution.
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33

Okubo, H., K. Itou, S. Tanaka, N. Watanabe, N. Kashiwagi, and F. Obata. "Analysis of the HLA-DR gene frequencies in Japanese cases of juveniles rheumatoid arthritis and rheumatoid arthritis by oligonucleotide DNA typing." Rheumatology International 13, no. 2 (June 1993): 65–69. http://dx.doi.org/10.1007/bf00307736.

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34

Theobald, M., and D. Bunjes. "Pretransplant detection of human minor histocompatibility antigen- specific naive and memory interleukin-2-secreting T cells within class I major histocompatibility complex (MHC)-restricted CD8+ and class II MHC-restricted CD4+ T-cell subsets." Blood 82, no. 1 (July 1, 1993): 298–306. http://dx.doi.org/10.1182/blood.v82.1.298.bloodjournal821298.

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Recent studies have shown that host-reactive interleukin-2 (IL-2)- secreting donor T lymphocytes (TI) are critically involved in the development of acute graft-versus-host disease (GVHD) after allogeneic HLA-identical sibling bone marrow transplantation (BMT). To further characterize the responding TI, we determined the frequency of pretransplant IL-2-secreting TI-precursors (TI-p) between eight HLA-A, - B, -C, -DR, and -DQ-identical sibling donor-host pairs in both the graft-versus-host (GVH) and the host-versus-graft (HVG) direction. High frequencies of pretransplant host-reactive donor TI-p (1/18,000 to 1/49,000) were detectable in five patients with grade II acute GVHD. Donor-reactive host TI-p (1/3,700 to 1/31,000) were observed in previously in vivo primed (n = 5) and unprimed (n = 1) patients. In two pairs tested after previous in vivo priming, pretransplant donor- reactive host TI-p were highly enriched within the CD45RO+ memory T- cell subset. Previously unprimed host-reactive donor TI-p occurred in almost equal frequencies within CD45RO+ and CD45RO- T cells. Both CD4+ and CD8+ T-cell subsets contributed in comparable frequencies to host- and donor-reactive TI-p. Recognition of minor histocompatibility (mH) antigens by CD8+ TI-p appeared to be class I major histocompatibility complex (MHC)-restricted, whereas CD4+ TI-p operated in a class II (HLA- DR) MHC-restricted fashion. Even between oligonucleotide-defined HLA- DPB1-disparate sibling donor-host pairs (n = 3), either responding T- cell subset was found to recognize cellularly defined mH antigens. These data indicate that various T-cell subsets contribute to host- and donor-reactive IL-2-secreting TI in allogeneic sibling BMT.
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35

Louie, Wilson, Max W. Shen, Zakir Tahiry, Sophia Zhang, Daniel Worstell, Christopher A. Cassa, Richard I. Sherwood, and David K. Gifford. "Machine learning based CRISPR gRNA design for therapeutic exon skipping." PLOS Computational Biology 17, no. 1 (January 8, 2021): e1008605. http://dx.doi.org/10.1371/journal.pcbi.1008605.

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Restoring gene function by the induced skipping of deleterious exons has been shown to be effective for treating genetic disorders. However, many of the clinically successful therapies for exon skipping are transient oligonucleotide-based treatments that require frequent dosing. CRISPR-Cas9 based genome editing that causes exon skipping is a promising therapeutic modality that may offer permanent alleviation of genetic disease. We show that machine learning can select Cas9 guide RNAs that disrupt splice acceptors and cause the skipping of targeted exons. We experimentally measured the exon skipping frequencies of a diverse genome-integrated library of 791 splice sequences targeted by 1,063 guide RNAs in mouse embryonic stem cells. We found that our method, SkipGuide, is able to identify effective guide RNAs with a precision of 0.68 (50% threshold predicted exon skipping frequency) and 0.93 (70% threshold predicted exon skipping frequency). We anticipate that SkipGuide will be useful for selecting guide RNA candidates for evaluation of CRISPR-Cas9-mediated exon skipping therapy.
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36

Louie, Wilson, Max W. Shen, Zakir Tahiry, Sophia Zhang, Daniel Worstell, Christopher A. Cassa, Richard I. Sherwood, and David K. Gifford. "Machine learning based CRISPR gRNA design for therapeutic exon skipping." PLOS Computational Biology 17, no. 1 (January 8, 2021): e1008605. http://dx.doi.org/10.1371/journal.pcbi.1008605.

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Restoring gene function by the induced skipping of deleterious exons has been shown to be effective for treating genetic disorders. However, many of the clinically successful therapies for exon skipping are transient oligonucleotide-based treatments that require frequent dosing. CRISPR-Cas9 based genome editing that causes exon skipping is a promising therapeutic modality that may offer permanent alleviation of genetic disease. We show that machine learning can select Cas9 guide RNAs that disrupt splice acceptors and cause the skipping of targeted exons. We experimentally measured the exon skipping frequencies of a diverse genome-integrated library of 791 splice sequences targeted by 1,063 guide RNAs in mouse embryonic stem cells. We found that our method, SkipGuide, is able to identify effective guide RNAs with a precision of 0.68 (50% threshold predicted exon skipping frequency) and 0.93 (70% threshold predicted exon skipping frequency). We anticipate that SkipGuide will be useful for selecting guide RNA candidates for evaluation of CRISPR-Cas9-mediated exon skipping therapy.
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37

Chan, Kai-Chieh, Che-Ming Wu, Wan-Ling Ho, and Ping-Chin Lai. "Association of Ménière Disease with Human Leukocyte Antigen in Taiwanese Population." Ear, Nose & Throat Journal 97, no. 12 (December 2018): 396–402. http://dx.doi.org/10.1177/014556131809701208.

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The etiology of Ménière disease (MD) is multifactorial; genetic factors seem to play an important role. The associations between MD and human leukocyte antigen (HLA) status have been studied previously in several populations and have shown that the HLA alleles imparting susceptibility varied. In the present study, we explored HLA status in Taiwanese patients with definitive MD. HLA was typed via polymerase chain reaction, sequence-specific oligonucleotide genotyping in 35 patients with MD diagnosed using the criteria of the American Academy of Otolaryngology–Head and Neck Surgery and 70 unrelated healthy controls. HLA allele association tests were used to evaluate differences in allelic frequencies between the patients and controls. The allelic frequency of HLA-A∗11 was significantly greater in MD patients than in controls (52.9 vs. 31.4%, odds ratio: 2.45, 95% confidence interval: 1.4 to 4.4, p = 0.004, p corrected = 0.03). Thus, A∗11 may be a useful HLA biomarker in Taiwanese patients with MD. Further larger-scale studies are required.
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38

van Helden, J., B. André, and J. Collado-Vides. "Extracting regulatory sites from the upstream region of yeast genes by computational analysis of oligonucleotide frequencies 1 1Edited by G. von Heijne." Journal of Molecular Biology 281, no. 5 (September 1998): 827–42. http://dx.doi.org/10.1006/jmbi.1998.1947.

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39

Al Yafei, Zain, Abdelhafidh Hajjej, Marion Alvares, Ayeda Al Mahri, Amre Nasr, Rajaa Mirghani, Ali Al Obaidli, et al. "Analysis of the Origin of Emiratis as Inferred from a Family Study Based on HLA-A, -C, -B, -DRB1, and -DQB1 Genes." Genes 14, no. 6 (May 26, 2023): 1159. http://dx.doi.org/10.3390/genes14061159.

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In this study, we investigated HLA class I and class II allele and haplotype frequencies in Emiratis and compared them to those of Asian, Mediterranean, and Sub-Saharan African populations. Methods: Two-hundred unrelated Emirati parents of patients selected for bone marrow transplantation were genotyped for HLA class I (A, B, C) and class II (DRB1, DQB1) genes using reverse sequence specific oligonucleotide bead-based multiplexing. HLA haplotypes were assigned with certainty by segregation (pedigree) analysis, and haplotype frequencies were obtained by direct counting. HLA class I and class II frequencies in Emiratis were compared to data from other populations using standard genetic distances (SGD), Neighbor-Joining (NJ) phylogenetic dendrograms, and correspondence analysis. Results: The studied HLA loci were in Hardy–Weinberg Equilibrium. We identified 17 HLA-A, 28 HLA-B, 14 HLA-C, 13 HLA-DRB1, and 5 HLA-DQB1 alleles, of which HLA-A*02 (22.2%), -B*51 (19.5%), -C*07 (20.0%), -DRB1*03 (22.2%), and -DQB1*02 (32.8%) were the most frequent allele lineages. DRB1*03~DQB1*02 (21.2%), DRB1*16~DQB1*05 (17.3%), B*35~C*04 (11.7%), B*08~DRB1*03 (9.7%), A*02~B*51 (7.5%), and A*26~C*07~B*08~DRB1*03~DQB1*02 (4.2%) were the most frequent two- and five-locus HLA haplotypes. Correspondence analysis and dendrograms showed that Emiratis were clustered with the Arabian Peninsula populations (Saudis, Omanis and Kuwaitis), West Mediterranean populations (North Africans, Iberians) and Pakistanis, but were distant from East Mediterranean (Turks, Albanians, Greek), Levantine (Syrians, Palestinians, Lebanese), Iranian, Iraqi Kurdish, and Sub-Saharan populations. Conclusions: Emiratis were closely related to Arabian Peninsula populations, West Mediterranean populations and Pakistanis. However, the contribution of East Mediterranean, Levantine Arab, Iranian, and Sub-Saharan populations to the Emiratis’ gene pool appears to be minor.
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40

Sahin Tekin, Melisa, Goknur Yorulmaz, Emel Yantir, Eren Gunduz, and Ertugrul Colak. "A Novel Finding of an HLA Allele’s and a Haplotype’s Relationship with SARS-CoV-2 Vaccine-Associated Subacute Thyroiditis." Vaccines 10, no. 12 (November 23, 2022): 1986. http://dx.doi.org/10.3390/vaccines10121986.

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Subacute thyroiditis (SAT) is a thyroid disease associated with viral infections. Its relationship with major histocompatibility complex (MHC) antigens was shown before. SAT cases triggered by different types of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have been reported. In this study, human leukocyte antigen (HLA) genotypes of 27 SAT patients (13 vaccine-associated (V-SAT) and 14 non-SARS-CoV-2-infection non-vaccine-associated (non-V-SAT)) were compared with those of 362 healthy donors. HLA analyses were performed with low-resolution DNA-based sequence-specific oligonucleotide or sequence-specific primer methods. Statistical analyses were performed using IBM SPSS Statistics 25 and Stata/MP 14.1 with the hapipf function. Allele and haplotype frequencies were estimated by PyPop and gene[RATE] tool programs. The allele frequencies of HLA-A*11, HLA-B*35, and HLA-C*04 were higher in the patient groups. Both the allele frequency of HLA-A*11 and the haplotype frequency of A*11-B*35-C*04 were higher in the V-SAT group. The A*11-B*35-C*04 haplotype, including all three loci of MHC class I genes, is shown to be associated with the disease for the first time, especially in the V-SAT group. This finding will contribute to a better understanding of the etiopathogenesis of vaccine-associated SAT and the role of HLA genotypes in the functioning mechanisms of the SARS-CoV-2 vaccines.
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41

Du, Wei-Dong, Gang Chen, Hui-Min Cao, Qing-Hui Jin, Rong-Feng Liao, Xiang-Cheng He, Da-Ben Chen, et al. "A Simple Oligonucleotide Biochip Capable of Rapidly Detecting Known Mitochondrial DNA Mutations in Chinese Patients with Leber’S Hereditary Optic Neuropathy (LHON)." Disease Markers 30, no. 4 (2011): 181–90. http://dx.doi.org/10.1155/2011/340723.

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Leber's hereditary optic neuropathy (LHON) is a maternally transmitted disease. Clinically, no efficient assay protocols have been available. In this study, we aimed to develop an oligonucleotide biochip specialized for detection of known base substitution mutations in mitochondrial DNA causing LHON and to investigate frequencies of LHON relevant variants in Anhui region of China. Thirty-two pairs of oligonucleotide probes matched with the mutations potentially linked to LHON were covalently immobilized. Cy5-lablled targets were amplified from blood DNA samples by a multiplex PCR method. Two kinds of primary mutations 11778 G > A and 14484 T > C from six confirmed LHON patients were interrogated to validate this biochip format. Further, fourteen Chinese LHON pedigrees and twenty-five unrelated healthy individuals were investigated by the LHON biochip, direct sequencing and pyrosequencing, respectively. The biochip was found to be able efficiently to discriminate homoplasmic and heteroplasmic mtDNA mutations in LHON. Biochip analysis revealed that twelve of eighteen LHON symptomatic cases from the 14 Chinese pedigree harbored the mutations either 11778G > A, 14484T > C or 3460G > A, respectively, accounting for 66.7%. The mutation 11778G > A in these patients was homoplasmic and prevalent (55.5%, 10 of 18 cases). The mutations 3460G > A and 3394T > C were found to co-exist in one LHON case. The mutation 13708G > A appeared in one LHON pedigree. Smaller amount of sampling and reaction volume, easier target preparation, fast and high-throughput were the main advantages of the biochip over direct DNA sequencing and pyrosequencing. Our findings suggested that primary mutations of 11778G > A, 14484T > C or 3460G > A are main variants of mtDNA gene leading to LHON in China. The biochip would easily be implemented in clinical diagnosis.
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42

Nikaein, A., D. Cluff, R. Fishbeck, L. Dombrausky, and J. Fay. "Serologic and oligonucleotide typing of HLA antigens, MLC and helper and cytotoxic T cell frequencies in selection of unrelated bone marrow transplant donors." Human Immunology 40 (January 1994): 25. http://dx.doi.org/10.1016/0198-8859(94)91708-6.

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43

Thonnard, Joëlle, Marianne Philippe, Ming-Yu Cao, Naïma Deggouj, Jean-Claude Osselaer, Michel Gersdorff, and Jean-Paul Tomasi. "HLA Class II-Associated Genetic Susceptibility in Idiopathic Progressive Sensorineural Hearing Loss." Annals of Otology, Rhinology & Laryngology 105, no. 8 (August 1996): 628–33. http://dx.doi.org/10.1177/000348949610500808.

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To investigate the association between genes in the major histocompatibility complex and inner ear disease susceptibility at the DNA level, high-resolution genotyping for HLA class II (HLA-DR, -DQ, -DP) was performed by polymerase chain reaction-sequence-specific oligonucleotide reverse dot blot and polymerase chain reaction-restriction fragment length polymorphism analysis in 34 patients with idiopathic progressive sensorineural hearing loss (PSHL) and in 214 controls. The frequencies of DRB1*0301, DRB3*0101, DQB1*0201, and DPB1*0401 were significantly increased in patients with idiopathic PSHL compared with controls. The DQB1*0301 allele was significantly decreased in the patients. A linkage disequilibrium was probably responsible for the concomitant increase of both DRB1*0301 and DRB3*0101 alleles in patients. The increase of DQB1*0201 in patients was associated with the DRB1*0301 allele. In addition, the telomeric DPB 1*0401 allele may act as an independent risk factor. The DQB1*0301 allele may have a protective role in the pathogenesis of idiopathic PSHL. These results suggest that the specific HLA class II gene products may confer susceptibility or resistance to idiopathic PSHL.
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44

Bohlin, Jon. "Genomic Signatures in Microbes—Properties and Applications." Scientific World JOURNAL 11 (2011): 715–25. http://dx.doi.org/10.1100/tsw.2011.70.

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The ratio of genomic oligonucleotide frequencies relative to the mean genomic AT/GC content has been shown to be similar for closely related species and, therefore, said to reflect a “genomic signature”. The genomic signature has been found to be more similar within genomes than between closely related genomes. Furthermore, genomic signatures of closely related organisms are, in turn, more similar than more distantly related organisms. Since the genomic signature is remarkably stable within a genome, it can be extracted from only a fraction of the genomic DNA sequence. Genomic signatures, therefore, have many applications. The most notable examples include recognition of pathogenicity islands in microbial genomes and identification of hosts from arbitrary DNA sequences, the latter being of great importance in metagenomics. What shapes the genomic signature in microbial DNA has been readily discussed, but difficult to pinpoint exactly. Most attempts so far have mainly focused on correlations fromin silicodata. This mini-review seeks to summarize possible influences shaping the genomic signature and to survey a set of applications.
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45

Calamita, Zamir, Andrea Bronhara Pelá, Márcia Gamberini, Wilson Baleotti Júnior, Odilon Marques de Almeida Filho, Marcelo O. Ruiz, Dione G. Arevalo, and Antônio Fabron Júnior. "HLA among Brazilian patients with spontaneous chronic urticaria and positive autologous serum skin test." Anais Brasileiros de Dermatologia 87, no. 4 (August 2012): 578–83. http://dx.doi.org/10.1590/s0365-05962012000400010.

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BACKGROUND: An association between class I and II alleles of the major histocompatibility complex and idiopathic chronic urticaria has previously been observed in different populations, but there are still no studies on Brazilian populations in this regard. OBJECTIVE: The involvement of the major histocompatibility complex classes I and II (loci A, B and DR) in Brazilian patients with idiopathic chronic urticaria and a positive autologous serum skin test was investigated and compared with a healthy population group. METHODS: DNA was extracted from the blood of 42 patients with idiopathic chronic urticaria and major histocompatibility complex classes I and II alleles were determined using the polymerase chain reaction and a laboratory test for oligonucleotide hybridization using a single-filament probe. The frequencies of these alleles in patients with chronic urticaria were compared with the frequencies in 1000 genetically unrelated voluntary blood donors from the same region of Brazil. The diagnosis of idiopathic chronic urticaria was based on the patients' clinical history and routine laboratory tests. Only the patients with positive autologous serum skin test were selected. The allele distribution resulted from the patient and control groups were analyzed using odds ratios and 95% confidence intervals. RESULTS: No statistically significant differences were found between the positive autologous serum skin test patients with chronic urticaria and the control group. CONCLUSIONS: We found that in this population group, there was no specific association between the HLA alleles studied and chronic urticaria. We believe that further population studies are needed in order to investigate the possible existence of this association.
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46

Pearce, Richard J., Chris Drakeley, Daniel Chandramohan, Frank Mosha, and Cally Roper. "Molecular Determination of Point Mutation Haplotypes in the Dihydrofolate Reductase and Dihydropteroate Synthase of Plasmodium falciparum in Three Districts of Northern Tanzania." Antimicrobial Agents and Chemotherapy 47, no. 4 (April 2003): 1347–54. http://dx.doi.org/10.1128/aac.47.4.1347-1354.2003.

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ABSTRACT The antimalarial combination of sulfadoxine and pyrimethamine (SP) was introduced as first-line treatment for uncomplicated malaria in Tanzania during 2001 following 18 years of second-line use. The genetic determinants of in vitro resistance to the two drugs individually are shown to be point mutations at seven sites in the dihydrofolate reductase gene (dhfr) conferring resistance to pyrimethamine and five sites in the dihydropteroate synthase (dhps) gene conferring resistance to sulfadoxine. Different combinations of mutations within each gene confer differing degrees of insensitivity, but information about the frequency with which allelic haplotypes occur has been lacking because of the complicating effects of multiple infection. Here we used a novel high-throughput sequence-specific oligonucleotide probe-based approach to examine the present resistance status of three Plasmodium falciparum populations in northern Tanzania. By using surveys of asymptomatic infections and screening for the presence of all known point mutations in dhfr and dhps genes, we showed that just five dhfr and three dhps allelic haplotypes are present. High frequencies of both triple-mutant dhfr and double-mutant dhps mutant alleles were found in addition to significant interregional heterogeneity in allele frequency. In vivo studies have shown that the cooccurrence of three dhfr mutations and two dhps mutations in an infection prior to treatment is statistically predictive of treatment failure. We have combined data for both loci to determine the frequency of two-locus genotypes. The triple-dhfr/double-dhps genotype is present in all three regions with frequencies ranging between 30 and 63%, indicating that treatment failure rates are likely to be high.
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47

Vickerman, M. M., S. Iobst, A. M. Jesionowski, and S. R. Gill. "Genome-Wide Transcriptional Changes in Streptococcus gordonii in Response to Competence Signaling Peptide." Journal of Bacteriology 189, no. 21 (August 24, 2007): 7799–807. http://dx.doi.org/10.1128/jb.01023-07.

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ABSTRACT Streptococcus gordonii is a primary colonizer of the multispecies biofilm on tooth surfaces forming dental plaque and a potential agent of endocarditis. The recent completion of the genome sequence of the naturally competent strain Challis allowed the design of a spotted oligonucleotide microarray to examine a genome-wide response of this organism to environmental stimuli such as signal peptides. Based on temporal responses to synthetic competence signaling peptide (CSP) as indicated by transformation frequencies, the S. gordonii transcriptome was analyzed at various time points after CSP exposure. Microarray analysis identified 35 candidate early genes and 127 candidate late genes that were up-regulated at 5 and 15 min, respectively; these genes were often grouped in clusters. Results supported published findings on S. gordonii competence, showing up-regulation of 12 of 16 genes that have been reported to affect transformation frequencies in this species. Comparison of CSP-induced S. gordonii transcriptomes to results published for Streptococcus pneumoniae strains identified both conserved and species-specific genes. Putative intergenic regulatory sites, such as the conserved combox sequence thought to be a binding site for competence sigma factor, were found preceding S. gordonii late responsive genes. In contrast, S. gordonii early CSP-responsive genes were not preceded by the direct repeats found in S. pneumoniae. These studies provide the first insights into a genome-wide transcriptional response of an oral commensal organism. They offer an extensive analysis of transcriptional changes that accompany competence in S. gordonii and form a basis for future intra- and interspecies comparative analyses of this ecologically important phenotype.
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48

Revenko, Alexey, Larissa S. Carnevalli, Charles Sinclair, Ben Johnson, Alison Peter, Molly Taylor, Lisa Hettrick, et al. "Direct targeting of FOXP3 in Tregs with AZD8701, a novel antisense oligonucleotide to relieve immunosuppression in cancer." Journal for ImmunoTherapy of Cancer 10, no. 4 (April 2022): e003892. http://dx.doi.org/10.1136/jitc-2021-003892.

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BackgroundThe Regulatory T cell (Treg) lineage is defined by the transcription factor FOXP3, which controls immune-suppressive gene expression profiles. Tregs are often recruited in high frequencies to the tumor microenvironment where they can suppress antitumor immunity. We hypothesized that pharmacological inhibition of FOXP3 by systemically delivered, unformulated constrained ethyl-modified antisense oligonucleotides could modulate the activity of Tregs and augment antitumor immunity providing therapeutic benefit in cancer models and potentially in man.MethodsWe have identified murine Foxp3 antisense oligonucleotides (ASOs) and clinical candidate human FOXP3 ASO AZD8701. Pharmacology and biological effects of FOXP3 inhibitors on Treg function and antitumor immunity were tested in cultured Tregs and mouse syngeneic tumor models. Experiments were controlled by vehicle and non-targeting control ASO groups as well as by use of multiple independent FOXP3 ASOs. Statistical significance of biological effects was evaluated by one or two-way analysis of variance with multiple comparisons.ResultsAZD8701 demonstrated a dose-dependent knockdown of FOXP3 in primary Tregs, reduction of suppressive function and efficient target downregulation in humanized mice at clinically relevant doses. Surrogate murine FOXP3 ASO, which efficiently downregulated Foxp3 messenger RNA and protein levels in primary Tregs, reduced Treg suppressive function in immune suppression assays in vitro. FOXP3 ASO promoted more than 70% reduction in FOXP3 levels in Tregs in vitro and in vivo, strongly modulated Treg effector molecules (eg, ICOS, CTLA-4, CD25 and 4-1BB), and augmented CD8+ T cell activation and produced antitumor activity in syngeneic tumor models. The combination of FOXP3 ASOs with immune checkpoint blockade further enhanced antitumor efficacy.ConclusionsAntisense inhibitors of FOXP3 offer a promising novel cancer immunotherapy approach. AZD8701 is being developed clinically as a first-in-class FOXP3 inhibitor for the treatment of cancer currently in Ph1a/b clinical trial (NCT04504669).
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49

Guidot, Alice, Erica Lumini, Jean-Claude Debaud, and Roland Marmeisse. "The Nuclear Ribosomal DNA Intergenic Spacer as a Target Sequence To Study Intraspecific Diversity of the Ectomycorrhizal Basidiomycete Hebeloma cylindrosporum Directly on Pinus Root Systems." Applied and Environmental Microbiology 65, no. 3 (March 1, 1999): 903–9. http://dx.doi.org/10.1128/aem.65.3.903-909.1999.

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ABSTRACT Polymorphism of the nuclear ribosomal DNA intergenic spacer (IGS) of the ectomycorrhizal basidiomycete Hebeloma cylindrosporum was studied to evaluate whether this sequence could be used in field studies to estimate the diversity of strains forming mycorrhizas on individual Pinus pinaster root systems. This sequence was amplified by PCR from 125 haploid homokaryotic strains collected in 14 P. pinaster stands along the Atlantic coast of France by using conserved oligonucleotide primers. Restriction enzyme digestion of the amplified 3.4-kbp-long IGS allowed us to characterize 24 alleles whose frequencies differed. Nine of these alleles were found only once, whereas about 60% of the strains contained four of the alleles. Local populations could be almost as diverse as the entire population along a 150-km stretch of coastline that was examined; for example, 13 alleles were found in a single forest stand. The IGS from one strain was partially sequenced, and the sequence data were used to design oligonucleotides which allowed separate PCR amplification of three different segments of the IGS. Most polymorphisms observed among the full-length IGS regions resulted from polymorphisms in an internal ca. 1,500-bp-long sequence characterized by length variations that may have resulted from variable numbers of a T2AG3 motif. This internal polymorphic sequence could not be amplified from the genomes of nine other Hebeloma species. Analysis of this internal sequence amplified from the haploid progenies of 10 fruiting bodies collected in a 70-m2 area resulted in identification of six allelic forms and seven distinct diplotypes out of the 21 possible different combinations. Moreover, optimization of the PCR conditions resulted in amplification of this sequence from more than 80% of the DNA samples extracted from individual H. cylindrosporum infectedP. pinaster mycorrhizal root tips, thus demonstrating the usefulness of this sequence for studying the below-ground diversity of mycorrhizas formed by genets belonging to the same fungal species.
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50

Hernández-Hernández, Dulce M., Ricardo M. Cerda-Flores, Teresa Juárez-Cedillo, Julio Granados-Arriola, Gilberto Vargas-Alarcón, Teresa Apresa-García, Isabel Alvarado-Cabrero, Alejandro García-Carrancá, Mauricio Salcedo-Vargas, and Alejandro Mohar-Betancourt. "Human Leukocyte Antigens I and II Haplotypes Associated With Human Papillomavirus 16-Positive Invasive Cervical Cancer in Mexican Women." International Journal of Gynecologic Cancer 19, no. 6 (July 2009): 1099–106. http://dx.doi.org/10.1111/igc.0b013e3181a83cf4.

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Infection with human papillomavirus (HPV), mainly HPV type 16, is the major etiologic factor associated with cervical cancer (CC), but HPV infection alone is not sufficient for progression of precursor lesions. Host genetic susceptibility may lead to abnormal immune response resulting from virus persistence. Several studies have suggested a possible association with specific human leukocyte antigen (HLA) class I and II alleles and CC, but results are not consistent. The association of genetic HLA class I (A and B) and HLA class II (DR*B1 and DQ*B1) haplotypes with HPV16-positive CC (n = 104) and base population controls (n = 104) was evaluated in this Mexican population study. Sequence-specific primer HLA genes were determined by polymerase chain reaction (PCR)-based methods in peripheral blood cell counts (PCR sequence-specific oligonucleotides). The cervical swabs of 208 women were tested for HPV16 by Hybrid Capture II. Allele and haplotype HLA frequencies, Hardy-Weinberg tests, and a haplotype homogeneity test were estimated using the Arlequin software v. 3.01. Odds ratio (OR) was calculated to compare cases and control women. Consistent associations across other studies in women with CC and infected by HPV16 were observed for HLA-DRB1*15 (OR, 3.9; 95% CI, 1.6-10.2) and the haplotype DRB1*15 DQB1*0602 (OR, 4.1; 95% CI, 1.4-12.7) compared with control women. The HLA-A2-B44-DR4-DQ*0302, HLA-A24-B35-DR16-DQ*0301, and HLA-A2-B40-DR4-DQ*0302 haplotypes showed a positive association with CC (OR, >1), whereas HLA-A2-B39-DR4-DQ*0302, HLA-A24-B35-DR4-DQ*0302, and HLA-A68-B40-DR4-DQ*0302 showed a negative association (OR, <1). These results support the hypothesis that some HLA class I and II haplotypes could be involved with susceptibility for developing CC.Abbreviations:Cervical Cancer-CC, confidence interval-CI, human leukocyte antigens-HLA, human papillomavirus-HPV, odds ratio-OR, polymerase chain reaction-PCR, relative risk-RR, relative light units-RLU, ribonucleic acid-RNA, sequence-sensitive oligonucleotide-SSO
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