Effects of the multiple O-glycosylation states on antibody recognition of the immunodominant motif in MUC1 extracellular tandem repeats

MedChemComm ◽  
2016 ◽  
Vol 7 (6) ◽  
pp. 1102-1122 ◽  
Author(s):  
Shobith Rangappa ◽  
Gerard Artigas ◽  
Risho Miyoshi ◽  
Yasuhiro Yokoi ◽  
Shun Hayakawa ◽  
...  
Keyword(s):  
Tandem Repeat ◽  
Tandem Repeats ◽  
Antibody Recognition ◽  
Repeat Domain

The conformational impact of the clusteredO-glycans strongly influences recognition by antibodies of the cancer-relevant epitope in the MUC1 extracellular tandem repeat domain.

scholarly journals Human mucin gene MUC4: organization of its 5′-region and polymorphism of its central tandem repeat array

1998 ◽  
Vol 332 (3) ◽  
pp. 739-748 ◽  
Author(s):  
Séverine NOLLET ◽  
Nicolas MONIAUX ◽  
Jacques MAURY ◽  
Danièle PETITPREZ ◽  
Pierre DEGAND ◽  
...  
Keyword(s):  
Signal Peptide ◽  
Tandem Repeat ◽  
Tandem Repeats ◽  
Cysteine Residue ◽  
Coding Region ◽  
Exon 2 ◽  
Repeat Array ◽  
Mucin Gene ◽  
Repeat Domain ◽  
Tandem Repeat Array

In a previous study we isolated a partial cDNA with a tandem repeat of 48 bp, which allowed us to map a novel human mucin gene named MUC4to chromosome 3q29. Here we report the organization and sequence of the 5´-region and its junction with the tandem repeat array of MUC4. Analysis of three overlapping genomic clones allowed us to obtain a partial restriction map of MUC4 and to locate the complete 48 bp tandem repeat domain on a PstI/EcoRI genomic fragment that exhibits a very large variation in number of tandem repeats (7–19 kb). cDNA clonal extension allowed us to obtain the entire 5´ coding region of MUC4. Exon 1 consists of a 5´ untranslated region and an 82 bp fragment encoding the signal peptide. This latter shows a high degree of similarity to the signal peptide of another apomucin, ASGP-1. Exon 2 is extremely large and contains a unique sequence that is followed by the whole tandem repeat domain. It encodes only one cysteine residue, making MUC4 different from mucin genes belonging to the 11p15.5 family. Moreover, an intron downstream from the tandem repeat array consists mainly of a 15 bp tandem repeat that exhibits a polymorphism in having a variable number of tandem repeats.

scholarly journals Slipped-Strand Mispairing at Noncontiguous Repeats in Poecilia reticulata: A Model for Minisatellite Birth

Genetics ◽  
2000 ◽  
Vol 155 (3) ◽  
pp. 1313-1320 ◽  
Author(s):  
John S Taylor ◽  
Felix Breden
Keyword(s):  
Tandem Repeat ◽  
Poecilia Reticulata ◽  
Tandem Repeats ◽  
Phylogenetic Reconstruction ◽  
Variable Number ◽  
Repeat Motif ◽  
Raw Material ◽  
Direct Repeats ◽  
Mt Dna ◽  
Variable Number Tandem Repeats

Abstract The standard slipped-strand mispairing (SSM) model for the formation of variable number tandem repeats (VNTRs) proposes that a few tandem repeats, produced by chance mutations, provide the “raw material” for VNTR expansion. However, this model is unlikely to explain the formation of VNTRs with long motifs (e.g., minisatellites), because the likelihood of a tandem repeat forming by chance decreases rapidly as the length of the repeat motif increases. Phylogenetic reconstruction of the birth of a mitochondrial (mt) DNA minisatellite in guppies suggests that VNTRs with long motifs can form as a consequence of SSM at noncontiguous repeats. VNTRs formed in this manner have motifs longer than the noncontiguous repeat originally formed by chance and are flanked by one unit of the original, noncontiguous repeat. SSM at noncontiguous repeats can therefore explain the birth of VNTRs with long motifs and the “imperfect” or “short direct” repeats frequently observed adjacent to both mtDNA and nuclear VNTRs.

Association of the brain anion exchanger, AE3, with the repeat domain of ankyrin

1993 ◽  
Vol 105 (4) ◽  
pp. 1137-1142 ◽  
Author(s):  
C.W. Morgans ◽  
R.R. Kopito
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Anion Exchanger ◽  
Deletion Mutant ◽  
Tandem Repeats ◽  
Structural Homology ◽  
Terminal Domain ◽  
Repeat Domain ◽  
The Brain

The 89 kDa NH2-terminal domain of erythrocyte ankyrin is composed almost entirely of 22 tandem repeats of a 33 amino acid sequence and constitutes the binding site for the cytoplasmic NH2-terminal domain of the erythrocyte anion exchanger, AE1. We have developed an assay to evaluate the in vivo interaction between a fragment of ankyrin corresponding to this domain (ANK90) and two non-erythroid anion exchangers, AE2 and AE3, that share considerable structural homology with AE1. Association was assessed by co-immunoprecipitation of ANK90-anion exchanger complexes from detergent extracts of cells cotransfected with plasmids encoding the ankyrin fragment and the anion exchanger or mutants thereof. ANK90 was co-immunoprecipitated with AE1 but not with an AE1 deletion mutant lacking the cytoplasmic NH2-terminal domain. Using this assay, we show that the brain anion exchanger AE3, but not the closely related homologue, AE2, is capable of binding to ankyrin.

scholarly journals The MUC1 Cytoplasmic Tail and Tandem Repeat Domains Contribute to Mammary Oncogenesis in FVB Mice

2008 ◽  
Vol 1 ◽  
pp. BCBCR.S655
Author(s):  
Christine L. Hattrup ◽  
Judy M. Bradley ◽  
Kari L. Kotlarczyk ◽  
Cathy S. Madsen ◽  
Joseph G. Hentz ◽  
...  
Keyword(s):  
Mouse Models ◽  
Tandem Repeat ◽  
Late Onset ◽  
Cytoplasmic Tail ◽  
Mammary Carcinogenesis ◽  
Tumor Formation ◽  
Full Length ◽  
Relative Importance ◽  
Cancer Model ◽  
Repeat Domain

Background Though the importance of the transmembrane mucin MUC1 in mammary oncogenesis has long been recognized, the relative contributions of the cytoplasmic tail and tandem repeat domains are poorly understood. Methods To address this, mouse models of mammary carcinogenesis were created expressing full-length cytoplasmic tail-deleted, or tandem repeat-deleted MUC1 constructs. Results Overexpression of full-length MUC1 resulted in tumor formation in young mice (≤ 12 months); however, loss of either the cytoplasmic tail or the tandem repeat domain abrogated this oncogenic capacity. Aged mice in all strains developed late-onset mammary tumors similar to those previously described for the FVB background. Conclusions This study is the first spontaneous cancer model to address the relative importance of the cytoplasmic tail and tandem repeat domains to MUC1-driven mammary oncogenesis, and suggests that both of these domains are essential for tumor formation.

scholarly journals Ehrlichia chaffeensis TRP120 nucleomodulin binds DNA with disordered tandem repeat domain

PLoS ONE ◽  
2018 ◽  
Vol 13 (4) ◽  
pp. e0194891 ◽  
Author(s):  
Valerie J. Klema ◽  
Krishna Mohan Sepuru ◽  
Nadia Füllbrunn ◽  
Tierra R. Farris ◽  
Paige S. Dunphy ◽  
...  
Keyword(s):  
Tandem Repeat ◽  
Ehrlichia Chaffeensis ◽  
Repeat Domain

scholarly journals Accurate measurement of microsatellite length by disrupting its tandem repeat structure

2021 ◽  
Author(s):  
Dan Levy ◽  
Zihua Wang ◽  
Andrea Moffitt ◽  
Michael H. Wigler
Keyword(s):  
Tandem Repeat ◽  
Error Rate ◽  
Tandem Repeats ◽  
Clinical Applications ◽  
Error Rates ◽  
Sequence Motifs ◽  
High Error Rate ◽  
Repeat Structure ◽  
Flanking Regions ◽  
Simple Sequence

Replication of tandem repeats of simple sequence motifs, also known as microsatellites, is error prone and variable lengths frequently occur during population expansions. Therefore, microsatellite length variations could serve as markers for cancer. However, accurate error-free quantitation of microsatellite lengths is difficult with current methods because of a high error rate during amplification and sequencing. We have solved this problem by using partial mutagenesis to disrupt enough of the repeat structure so that it can replicate faithfully, yet not so much that the flanking regions cannot be reliably identified. In this work we use bisulfite mutagenesis to convert a C to a U, later read as T. Compared to untreated templates, we achieve three orders of magnitude reduction in the error rate per round of replication. By requiring two independent first copies of an initial template, we reach error rates below one in a million. We discuss potential clinical applications of this method.

scholarly journals Comprehensive genetic diagnosis of tandem repeat expansion disorders with programmable targeted nanopore sequencing

2021 ◽  
Author(s):  
Igor Stevanovski ◽  
Sanjog R. Chintalaphani ◽  
Hasindu Gamaarachchi ◽  
James M. Ferguson ◽  
Sandy S. Pineda ◽  
...  
Keyword(s):  
Tandem Repeat ◽  
Tandem Repeats ◽  
Fragile X ◽  
Genetic Diagnosis ◽  
Neuromuscular Diseases ◽  
Nanopore Sequencing ◽  
Molecular Tests ◽  
Genetic Landscape ◽  
Long Read ◽  
Short Tandem

ABSTRACTShort-tandem repeat (STR) expansions are an important class of pathogenic genetic variants. Over forty neurological and neuromuscular diseases are caused by STR expansions, with 37 different genes implicated to date. Here we describe the use of programmable targeted long-read sequencing with Oxford Nanopore’s ReadUntil function for parallel genotyping of all known neuropathogenic STRs in a single, simple assay. Our approach enables accurate, haplotype-resolved assembly and DNA methylation profiling of expanded and non-expanded STR sites. In doing so, the assay correctly diagnoses all individuals in a cohort of patients (n = 27) with various neurogenetic diseases, including Huntington’s disease, fragile X syndrome and cerebellar ataxia (CANVAS) and others. Targeted long-read sequencing solves large and complex STR expansions that confound established molecular tests and short-read sequencing, and identifies non-canonical STR motif conformations and internal sequence interruptions. Even in our relatively small cohort, we observe a wide diversity of STR alleles of known and unknown pathogenicity, suggesting that long-read sequencing will redefine the genetic landscape of STR expansion disorders. Finally, we show how the flexible inclusion of pharmacogenomics (PGx) genes as secondary ReadUntil targets can identify clinically actionable PGx genotypes to further inform patient care, at no extra cost. Our study addresses the need for improved techniques for genetic diagnosis of STR expansion disorders and illustrates the broad utility of programmable long-read sequencing for clinical genomics.One sentence summaryThis study describes the development and validation of a programmable targeted nanopore sequencing assay for parallel genetic diagnosis of all known pathogenic short-tandem repeats (STRs) in a single, simple test.

Contribution of ABO-Rhesus/Electrophoresis of hemoglobin methods and Short Tandem Repeats analysis in the determination of paternity in Burkina Faso, West Africa

2020 ◽  
Author(s):  
Missa Millogo ◽  
Serge Theophile Soubeiga ◽  
Bapio Valerie Jean Telesphore Bazie ◽  
Theodora Mahoukede Zohoncon ◽  
Albert Theophane Yonli ◽  
...  
Keyword(s):  
Tandem Repeat ◽  
Short Tandem Repeat ◽  
High Performance ◽  
Short Tandem Repeats ◽  
Tandem Repeats ◽  
Repeat Analysis ◽  
Paternity Index ◽  
Genetic Analyzer ◽  
Short Tandem

Abstract Background: the establishment of filiation by the current ABO, HLA, MNS, Kells and serum tests, pose a real reliability problem. It is then necessary to combine these methods with or to use high-performance methods such as microsatellite genetic analysis or short tandem repeats. This study aimed to compare the short tandem repeat technique with ABO/Rhesus system in combination with electrophoresis of hemoglobin. Methods: Fourteen (14) contested paternity trios were investigated. Blood samples were collected to determine blood groups using the Beth-Vincent method and the type of hemoglobin by electrophoresis. Blood spots on FTA paper were used for the analysis of 16 STR loci (D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818, FGA, Amel) by capillary electrophoresis on the ABI 31310 Genetic Analyzer. The generated sequences were analyzed with GeneMapper® software version 3.2.1. The data were analyzed to determine the paternity index and the probability of paternity. Results: Of the fourteen (14) trios studied, ten (10) cases were probable inclusion, three (03) cases were exclusion and one (01) case was an undetermined paternity outcome with the ABO-Rhesus/ electrophoresis of hemoglobin system. While the analysis of genetic polymorphisms in DNA gave five (05) inclusions versus nine (09) exclusions of paternity. Of the 10 probable inclusion cases given by the ABO-Rhesus/Electrophoresis of hemoglobin system, only 05 cases (50%) were confirmed for inclusion by Short tandem repeat analysis. Conclusion: The analysis of short tandem repeat with sixteen genetic markers is more reliable in determining paternity than ABO-Rhesus/hemoglobin electrophoresis techniques.

scholarly journals RepeatsDB in 2021: improved data and extended classification for protein tandem repeat structures

2020 ◽  
Vol 49 (D1) ◽  
pp. D452-D457
Author(s):  
Lisanna Paladin ◽  
Martina Bevilacqua ◽  
Sara Errigo ◽  
Damiano Piovesan ◽  
Ivan Mičetić ◽  
...  
Keyword(s):  
Protein Data Bank ◽  
Tandem Repeat ◽  
Tandem Repeats ◽  
Classification Scheme ◽  
Sequence Similarity ◽  
Protein Structures ◽  
Hierarchical Classification ◽  
Structural Similarity ◽  
Data Bank ◽  
Similarity Class

Abstract The RepeatsDB database (URL: https://repeatsdb.org/) provides annotations and classification for protein tandem repeat structures from the Protein Data Bank (PDB). Protein tandem repeats are ubiquitous in all branches of the tree of life. The accumulation of solved repeat structures provides new possibilities for classification and detection, but also increasing the need for annotation. Here we present RepeatsDB 3.0, which addresses these challenges and presents an extended classification scheme. The major conceptual change compared to the previous version is the hierarchical classification combining top levels based solely on structural similarity (Class > Topology > Fold) with two new levels (Clan > Family) requiring sequence similarity and describing repeat motifs in collaboration with Pfam. Data growth has been addressed with improved mechanisms for browsing the classification hierarchy. A new UniProt-centric view unifies the increasingly frequent annotation of structures from identical or similar sequences. This update of RepeatsDB aligns with our commitment to develop a resource that extracts, organizes and distributes specialized information on tandem repeat protein structures.

Variable Number of Tandem Repeats in Zygosity Diagnosis in Twins

1990 ◽  
Vol 39 (4) ◽  
pp. 473-477 ◽  
Author(s):  
S. Costanzi Porrini ◽  
A. Sciarra ◽  
N. Sulli ◽  
M. Piane ◽  
R. Gualtieri ◽  
...  
Keyword(s):  
Population Genetics ◽  
Tandem Repeat ◽  
Tandem Repeats ◽  
Variable Number ◽  
Hla Typing ◽  
Blood Group Antigens ◽  
Length Polymorphisms ◽  
Dna Restriction ◽  
Restriction Fragment Length

AbstractThe use of DNA restriction fragment length polymorphisms (RFLP) to analyze variable number of tandem repeat (VNTR) sequences dispersed in the human genome, has become a powerful tool for the study of population genetics due to the very substantial polymorphism involved. Because the markers usually employed for twin zygosity determination (such as sex combination, placentation, HLA typing, blood group antigens, etc) may not be uniformly informative, we propose the use of synthetic olygonucleotides, representing VNTR “core” sequences, for the determination of zygosity in twins.

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