Relevant bibliographies by topics / Length mutations

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Academic literature on the topic 'Length mutations'

Author: Grafiati
Published: 4 June 2021
Last updated: 1 February 2022

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Journal articles on the topic "Length mutations"

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Yun, Jiwon, Jung-Ah Kim, Byungjin Hwang, Hee Sue Park, Kyongok Im, Sung-Min Kim, Dajeong Jeong, Kyu Min Lim, Duhee Bang, and Dong Soon Lee. "Triple-Negative Myeloproliferative Neoplasms Vs. Calr, JAK2 or MPL-Mutated Myeloproliferative Neoplasms: Distinct Molecular Characteristics." Blood 132, Supplement 1 (November 29, 2018): 1772. http://dx.doi.org/10.1182/blood-2018-99-118013.

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Abstract Background: We compared the clinical, cytogenetic, molecular features, and telomere lengths of patients with triple negative MPN and MPN with any of CALR, JAK2 or MPL mutations. Methods: Target capture sequencing of 87 genes and molecular cytogenetic studies were performed in 61 Korean patients with MPN. Also, we searched the newly reported mutations and novel mutations in triple negative MPN [JAK2-G335D (germline), JAK2-F556V, JAK2-G571S (germline), JAK2-V625F (germline), MPL-T119I, MPL-S204F/P, MPL-E230G, MPL-V285E (germline), MPL-R321W (germline), MPL-Y591D, MPL-S505N and MPL-W515R]. We compared clinical and molecular characteristics between two groups. Additionally, we performed telomere quantitative FISH for 48 patients' samples and measured telomere/centromere ratios of them. Results: Among 61 patients, 13 patients showed mutations in CALR, 34 in JAK2, and 3 in MPL. All of JAK2 mutation and CALR mutation site were reported sites, but 2 among 5 mutation site of MPL were novel mutation [D128N, D261Y]. Twelve patients showed triple negative (7 of PMF 7, 2 of ET, and 3 of MPN-U) - they showed 8 different mutation sites among 6 different genes (ASXL1, DNMT3A, NPM1, POLG, SRSF2, and ZMYM3). NPM1, POLG, and ZMYM3 mutations were seen only in triple negative patients. NPM1 mutation was significantly higher in triple negative MPN (P=0.0301). In telomere length study, there was no statistical difference between triple negative group (T/C ratio mean 12.5) and CALR, JAK2 or MPL mutated group (T/C ratio mean 10.0). Although, MPN patients with telomere length shorter than normal control's lower 10% (7.04) showed poor prognosis (P=0.0045). Conclusions: Patients with triple negative MPN are characterized by high frequency of NPM1 mutation and less number of somatic mutations. Since the mutational analysis for diagnostic purposes is limited to exons 14 of JAK2, exon 10 of MPL and exon 9 of CALR at present, search for JAK2 and MPL mutations in other sites are essential in triple negative MPNs. Keywords: Myeloproliferative neoplasms, next-generation sequencing, triple negative MPN, chromosome, FISH, telomere Disclosures No relevant conflicts of interest to declare.
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Azaiez, Aïda, Éric F. Bouchard, Martine Jean, and François J. Belzile. "Length, orientation, and plant host influence the mutation frequency in microsatellites." Genome 49, no. 11 (November 2006): 1366–73. http://dx.doi.org/10.1139/g06-099.

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Microsatellites are simple, tandem DNA repeats that represent unstable regions of the genome. They undergo frequent changes in tract length by base additions or deletions due to DNA polymerase slippage during replication. To characterize factors affecting the frequency of spontaneous mutations occurring in microsatellites in plants, a reporter system was used in Arabidopsis thaliana and tomato ( Lycopersicon esculentum ). The β-glucuronidase (GUS) reporter system was used to measure the mutation frequency in various microsatellites (G7, G10, G13, G16, and C16) in somatic tissues. Our results indicate that this frequency increases with the number of repeats: a G16 tract was almost 80-fold more mutable than a G7 tract. Furthermore, the frequency of mutations depends on repeat orientation, as G16 was 3-fold more mutable than C16. The mutation rate was also found to differ markedly in Arabidopsis and tomato for an identical microsatellite. Indeed, Arabidopsis showed a 5-fold higher mutation frequency than tomato with the same G7 reporter construct. Finally, mutation in a G16 tract was frequent enough that mutations transmitted germinally to the next generation could be detected at a relatively high frequency.
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Whittaker, John C., Roger M. Harbord, Nicola Boxall, Ian Mackay, Gary Dawson, and Richard M. Sibly. "Likelihood-Based Estimation of Microsatellite Mutation Rates." Genetics 164, no. 2 (June 1, 2003): 781–87. http://dx.doi.org/10.1093/genetics/164.2.781.

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Abstract Microsatellites are widely used in genetic analyses, many of which require reliable estimates of microsatellite mutation rates, yet the factors determining mutation rates are uncertain. The most straightforward and conclusive method by which to study mutation is direct observation of allele transmissions in parent-child pairs, and studies of this type suggest a positive, possibly exponential, relationship between mutation rate and allele size, together with a bias toward length increase. Except for microsatellites on the Y chromosome, however, previous analyses have not made full use of available data and may have introduced bias: mutations have been identified only where child genotypes could not be generated by transmission from parents' genotypes, so that the probability that a mutation is detected depends on the distribution of allele lengths and varies with allele length. We introduce a likelihood-based approach that has two key advantages over existing methods. First, we can make formal comparisons between competing models of microsatellite evolution; second, we obtain asymptotically unbiased and efficient parameter estimates. Application to data composed of 118,866 parent-offspring transmissions of AC microsatellites supports the hypothesis that mutation rate increases exponentially with microsatellite length, with a suggestion that contractions become more likely than expansions as length increases. This would lead to a stationary distribution for allele length maintained by mutational balance. There is no evidence that contractions and expansions differ in their step size distributions.
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Birzu, C., A. Hillairet, M. Giry, N. Grandin, P. Verrelle, K. Mokhtari, Y. Marie, et al. "OS9.7 Telomere length, TERTp mutation and ALT status in adult diffuse gliomas." Neuro-Oncology 21, Supplement_3 (August 2019): iii19—iii20. http://dx.doi.org/10.1093/neuonc/noz126.065.

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Abstract BACKGROUND The current classification of adult diffuse gliomas integrates two alternative telomere maintenance mechanisms: reactivation of telomerase activity by TERT promoter (TERTp) mutations or ATRX mutations associated with alternative length telomere (ALT). We investigated here the relation between these two mechanisms, telomere length, and outcome in a large series of diffuse gliomas. MATERIAL AND METHODS We performed C-circle assay (CCA) to determine ALT status, determined telomere length in tumor (RTLt) and leukocyte (RTLl) in a cohort of 354 adult diffuse gliomas, and sequenced ATRX gene. We calculated an age-adjusted telomere score considering tumor and leukocyte (blood) telomere length and corrected by age. This score was used in univariate and multivariate survival analyses to evaluate the potential impact of telomere length on the prognosis of gliomas. We used the TCGA LGG-GBM dataset to validate our findings in an independent cohort. RESULTS RTLl and RTLt were associated with ATRX mutation and ALT phenotype, and negatively associated with age and TERTp mutations. ATRX mutations (found in 52% (64/123) of samples) were mostly transitions (C>T or T>C), and were associated with ALT phenotype. None of 1p/19q co-deleted oligodendrogliomas harbored an ALT phenotype. No patients with TERTp mutations had ALT phenotype except for a very small subgroup of patients (3/87, 3.4%) suggesting that multiple ways of telomere maintenance, may co-exist in a single tumor, probably expressed in different clones. Telomere age-adjusted score was independently associated with better outcome (HR= 0.73 [95% CI 0.56–0.97], p-value 0.03 adjusted for age, TERTp mutation, IDH mutation, 1p/19q co-deletion and WHO grade). These results were validated using the LGG-GBM TCGA dataset. CONCLUSION We unravel the relation between RTLl and RTLt, TERTp mutation and ALT phenotype and describe a novel telomere age-adjusted score independently associated with better prognosis in adult diffuse gliomas.
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Jiang, Xuejie, Changxin Yin, Junya Sun, Jiaying Cheng, Qiang Wang, Guopan Yu, Ling Jiang, et al. "Influence of FLT3-ITD Mutation and Length on the Treatment Response and Prognosis in Cytogenetically Normal AML Patients." Blood 132, Supplement 1 (November 29, 2018): 5245. http://dx.doi.org/10.1182/blood-2018-99-111063.

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Abstract BACKGROUND : Mutations of internal tandem duplication in FMS-like tyrosine kinase 3 (FLT3-ITD) contributed to poor prognosis in cytogenetically normal acute myeloid leukemia (CN-AML). FLT3 tyrosine kinase inhibitor sorafenib in combination with chemotherapy was applied to treat FLT3-ITD AML patients with limited efficacy. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) was considered as a potent therapeutic regimen in FLT3-ITD patients, but additional sorafenib maintenance was indispensable to support their long-term survival after allo-HSCT. Studies showed that increasing ITD size may be accompanied with decreasing OS and RFS in AML patients, but it remained controversial about the prognostic implication of ITD mutant lengths, the prognostic influence was important to evaluate in determining the therapeutic strategy for AML patients with different ITD lengths. METHODS: Total 185 CN-AML patients with and without FLT3-ITD mutations were enrolled in this study. We retrospectively studied the clinical characteristic, treatment response, survival and relapse risk after chemotherapy or allo-HSCT plus sorafenib in these patients. Distribution of ITD lengths detected in AML patients suggested two groups including long (≥70bp) and short ITD length (<70bp). Influence of FLT3-ITD mutation and its length were investigated after chemotherapy or allo-HSCT plus sorafenib. RESULT: FLT3-ITD mutations were detected in 15 percentage of AML patients, and associated with leukocytosis, high blast percentage in bone morrow (BM) and increased risk of treatment failure. FLT3-ITD mutations indicated decreased complete remission (CR) rate, overall survival (OS) and relapse-free survival (RFS), and increased relapse risk (RR) in AML patients after chemotherapy plus sorafenib. Patients with long ITD length (≥70bp) had worse OS and RFS, and more relapse probability than these with short ITD length (< 0bp) or FLT3-WT, but patients with short ITD length and FLT3-WT had the similar RFS and RR after chemotherapy. Allo-HSCT plus sorafenib maintenance significantly prolonged OS and RFS, decreased RR in FLT3-ITD patients, especially in these with long ITD length instead of those with short ITD length. CONCLUSION: Our findings indicated that FLT3-ITD mutation and long ITD length had negative effect on treatment response and prognosis in CN-AML patients. Allo-HSCT plus sorafenib maintenance was an effective strategy to improve survival and decrease relapse probability, abrogated disadvantage from long ITD length in FLT3-ITD patients. Disclosures No relevant conflicts of interest to declare.
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Comeron, Josep M., and Martin Kreitman. "The Correlation Between Intron Length and Recombination in Drosophila: Dynamic Equilibrium Between Mutational and Selective Forces." Genetics 156, no. 3 (November 1, 2000): 1175–90. http://dx.doi.org/10.1093/genetics/156.3.1175.

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Abstract Intron length is negatively correlated with recombination in both Drosophila melanogaster and humans. This correlation is not likely to be the result of mutational processes alone: evolutionary analysis of intron length polymorphism in D. melanogaster reveals equivalent ratios of deletion to insertion in regions of high and low recombination. The polymorphism data do reveal, however, an excess of deletions relative to insertions (i.e., a deletion bias), with an overall deletion-to-insertion events ratio of 1.35. We propose two types of selection favoring longer intron lengths. First, the natural mutational bias toward deletion must be opposed by strong selection in very short introns to maintain the minimum intron length needed for the intron splicing reaction. Second, selection will favor insertions in introns that increase recombination between mutations under the influence of selection in adjacent exons. Mutations that increase recombination, even slightly, will be selectively favored because they reduce interference among selected mutations. Interference selection acting on intron length mutations must be very weak, as indicated by frequency spectrum analysis of Drosophila intron length polymorphism, making the equilibrium for intron length sensitive to changes in the recombinational environment and population size. One consequence of this sensitivity is that the advantage of longer introns is expected to decrease inversely with the rate of recombination, thus leading to a negative correlation between intron length and recombination rate. Also in accord with this model, intron length differs between closely related Drosophila species, with the longest variant present more often in D. melanogaster than in D. simulans. We suggest that the study of the proposed dynamic model, taking into account interference among selected sites, might shed light on many aspects of the comparative biology of genome sizes including the C value paradox.
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McDew-White, Marina, Xue Li, Standwell C. Nkhoma, Shalini Nair, Ian Cheeseman, and Tim J. C. Anderson. "Mode and Tempo of Microsatellite Length Change in a Malaria Parasite Mutation Accumulation Experiment." Genome Biology and Evolution 11, no. 7 (July 1, 2019): 1971–85. http://dx.doi.org/10.1093/gbe/evz140.

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Abstract Malaria parasites have small extremely AT-rich genomes: microsatellite repeats (1–9 bp) comprise 11% of the genome and genetic variation in natural populations is dominated by repeat changes in microsatellites rather than point mutations. This experiment was designed to quantify microsatellite mutation patterns in Plasmodium falciparum. We established 31 parasite cultures derived from a single parasite cell and maintained these for 114–267 days with frequent reductions to a single cell, so parasites accumulated mutations during ∼13,207 cell divisions. We Illumina sequenced the genomes of both progenitor and end-point mutation accumulation (MA) parasite lines in duplicate to validate stringent calling parameters. Microsatellite calls were 99.89% (GATK), 99.99% (freeBayes), and 99.96% (HipSTR) concordant in duplicate sequence runs from independent sequence libraries, whereas introduction of microsatellite mutations into the reference genome revealed a low false negative calling rate (0.68%). We observed 98 microsatellite mutations. We highlight several conclusions: microsatellite mutation rates (3.12 × 10−7 to 2.16 × 10−8/cell division) are associated with both repeat number and repeat motif like other organisms studied. However, 41% of changes resulted from loss or gain of more than one repeat: this was particularly true for long repeat arrays. Unlike other eukaryotes, we found no insertions or deletions that were not associated with repeats or homology regions. Overall, microsatellite mutation rates are among the lowest recorded and comparable to those in another AT-rich protozoan (Dictyostelium). However, a single infection (>1011 parasites) will still contain over 2.16 × 103 to 3.12 × 104 independent mutations at any single microsatellite locus.
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Savage, Sharon A., Neelam Giri, Gabriela M. Baerlocher, Nick Orr, Peter M. Lansdorp, and Blanche P. Alter. "TINF2, a Component of the Shelterin Telomere Protection Complex, Is Mutated in Dyskeratosis Congenita." Blood 110, no. 11 (November 16, 2007): 835. http://dx.doi.org/10.1182/blood.v110.11.835.835.

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Abstract Dyskeratosis congenita (DC) is an inherited bone marrow failure syndrome characterized by the triad of abnormal nails, lacey reticular skin pigmentation, and oral leukoplakia. Patients with DC are at high risk of developing aplastic anemia, myelodysplastic syndrome and leukemia. Diagnosis of DC is challenging due to variability of the triad and heterogeneous clinical findings such as pulmonary and liver disease, avascular necrosis, esophageal or urethral stenosis and development delay. The unifying feature in DC is exceedingly short telomere lengths and defects in telomere biology. Gene mutations have been identified in DKC1 (X-linked), TERC and TERT (dominant, AD) and NOP10 (recessive), but approximately 60% of DC patients lack a known mutation. We identified a non-consanguineous family with AD DC and no mutations in DKCI, TERC or TERT. The first DC cases were monozygotic twin brothers (now deceased). Telomere length was determined by flow-FISH on the twins’ children (6 affected, 4 unaffected), wives, their 8 siblings and parents. Despite variable clinical phenotypes, the 6 affected individuals (1 female, 5 male) all had very short telomere lengths (<1st%ile for age). Unaffected relatives had normal telomere lengths. A single nucleotide polymorphism (SNP) genome-wide linkage screen (Human Linkage IVb, Illumina, Inc) was conducted using telomere length <1st%ile as the affected phenotype. SNPLINK was used to remove SNPs in linkage disequilibrium (D′=0.7, R2=0.4). Data were analyzed with GeneHunter under a parametric, AD, rare, highly-penetrant disease model. Evidence favoring linkage was found in a 17 megabase (Mb) region on chromosome 2p and a 3.1 Mb region on chromosome14q (LOD score=2.62 at both sites). Bi-directional sequence analysis of the two best candidate genes, DDX1 (2p) and TINF2 (14q) was conducted to identify mutations. A novel mutation, K280E, in TINF2 (protein name TIN2) was identified in the 6 living, affected family members but not in the 8 unaffected relatives, suggesting inheritance from the affected fathers. There were no mutations in DDX1. TINF2 was sequenced in 8 additional, unrelated DC probands without DKCI, TERC or TERT mutations and 7 with known mutations. An R282H mutation was present in 3 unrelated DC probands (1 Hoyeraal-Hreidarsson, 1 Revesz Syndrome). Another DC patient had an R282S mutation. TINF2 mutations were not present in unaffected relatives, DC probands with mutations in DKC1, TERC or TERT, or 298 controls. The mutation prevalence in DC probands represented in our cohort of patients with DC are DKC1 (18.8%), TERC (18.8%), TERT (6.2%), and TINF2 (31.2%). As a component of shelterin, the protein complex that stabilizes telomeres, TIN2 is highly evolutionarily conserved. It serves as a bridge between the three primary telomere DNA-binding proteins, TRF1, TRF2 and POT1 (via TPP1). In silico analyses predict that K280E, R282H and R282S are deleterious mutations. Functional studies are underway to characterize possible effects of these mutations on shelterin protein interactions. By focusing on telomere length as the affected phenotype, instead of the heterogeneous clinical features present in DC patients, we identified mutations in TINF2 and further validated telomere length as a diagnostic test for DC. This study demonstrates that TINF2 is the 5th gene mutated in DC, the 1st in Revesz Syndrome, and the 1st shelterin complex gene mutated in human disease.
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Du, Hong-Yan, Elena Pumbo, Jennifer Ivanovich, Ping An, Richard T. Maziarz, Ulrike M. Reiss, Deborah Chirnomas, et al. "TERC and TERT gene mutations in patients with bone marrow failure and the significance of telomere length measurements." Blood 113, no. 2 (January 8, 2009): 309–16. http://dx.doi.org/10.1182/blood-2008-07-166421.

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Abstract Dyskeratosis congenita (DC) is a rare inherited form of bone marrow failure (BMF) caused by mutations in telomere maintaining genes including TERC and TERT. Here we studied the prevalence of TERC and TERT gene mutations and of telomere shortening in an unselected population of patients with BMF at our medical center and in a selected group of patients referred from outside institutions. Less than 5% of patients with BMF had pathogenic mutations in TERC or TERT. In patients with BMF, pathogenic TERC or TERT gene mutations were invariably associated with marked telomere shortening (≪ 1st percentile) in peripheral blood mononuclear cells (PBMCs). In asymptomatic family members, however, telomere length was not a reliable predictor for the presence or absence of a TERC or TERT gene mutation. Telomere shortening was not pathognomonic of DC, as approximately 30% of patients with BMF due to other causes had PBMC telomere lengths at the 1st percentile or lower. We conclude that in the setting of BMF, measurement of telomere length is a sensitive but nonspecific screening method for DC. In the absence of BMF, telomere length measurements should be interpreted with caution.
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Shaver, Aaron C., and Paul D. Sniegowski. "Spontaneously Arising mutL Mutators in Evolving Escherichia coli Populations Are the Result of Changes in Repeat Length." Journal of Bacteriology 185, no. 20 (October 15, 2003): 6076–82. http://dx.doi.org/10.1128/jb.185.20.6076-6082.2003.

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ABSTRACT Over the course of thousands of generations of growth in a glucose-limited environment, 3 of 12 experimental populations of Escherichia coli spontaneously and independently evolved greatly increased mutation rates. In two of the populations, the mutations responsible for this increased mutation rate lie in the same region of the mismatch repair gene mutL. In this region, a 6-bp repeat is present in three copies in the gene of the wild-type ancestor of the experimental populations but is present in four copies in one of the experimental populations and two copies in the other. These in-frame mutations either add or delete the amino acid sequence LA in the MutL protein. We determined that the replacement of the wild-type sequence with either of these mutations was sufficient to increase the mutation rate of the wild-type strain to a level comparable to that of the mutator strains. Complementation of strains bearing the mutator mutations with wild-type copies of either mutL or the mismatch repair gene uvrD rescued the wild-type mutation rate. The position of the mutator mutations—in the region of MutL known as the ATP lid—suggests a possible deficiency in MutL's ATPase activity as the cause of the mutator phenotype. The similarity of the two mutator mutations (despite the independent evolutionary histories of the populations that gave rise to them) leads to a discussion of the potential adaptive role of DNA repeats.
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Dissertations / Theses on the topic "Length mutations"

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Gomes, Tiago Lopes. "Into the structure of human full-length Smad proteins and the impact of cancer mutations." Doctoral thesis, Universitat de Barcelona, 2019. http://hdl.handle.net/10803/667908.

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Signal transduction pathways are essential mechanisms that cells use to perform a myriad of biological processes that when aberrant, can cause serious diseases. Understanding the molecular basis of these pathways in detail can help us interpret these signaling cascades. The TGFβ (Transforming Growth Factor β) signaling pathway is one of the best-studied ones in metazoans. The main effectors of this pathway are the Smad transcription factors, protein family. The work described in this thesis postulated mechanisms correlating Smad protein structure with function using structural biology. This work has been devoted to the study of Smad full-length proteins, with an emphasis on Smad4 and Smad2. The project started with the production of full- length human Smad proteins, which required an optimized protocol to obtain homogeneous samples in milligram quantities. Once this step was achieved, we have proceeded to the acquisition of structural data combining several techniques (NMR, SAXS and Ion Mobility Mass Spectrometry), together with software development for data integration. The analysis of this information allowed us to obtain a description of the full-length ensemble of Smad2 and Smad4 proteins. The main findings stressed that the inter-domain linkers of Smad2 and Smad4 behave as intrinsically disordered proteins. Smad4 full- length is a monomeric and flexible protein in an equilibrium between elongated and more compact conformations. In solution, Smad4 is not predominantly in an auto- inhibited conformation and the MH1 and MH2 are independently functioning domains. Smad2 is an oligomeric protein populating a monomer- dimer-trimer equilibrium shaped by phosphorylation. Phosphorylation and MH1 deletion shift the equilibrium towards trimer formation, deletion of the C-terminal phosphosites abolishes trimer formation and the inter-domain association is concentration- dependent. We also analyzed how cancer mutations could affect protein structure and found that: Smad4 MH1 mutations mainly affect charged and hydrophobic residues. Cancer mutations seem to affect protein stability while maintaining DNA binding functionality. By comparing melting temperature analysis and molecular dynamics simulations, we proposed a mutational landscape mechanism for the Smad4 MH1 domain that exerts its effects by disrupting salt-bridge networks. Overall, we have established a framework for describing Smad protein structure from an intra- and inter-molecular perspective
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Gunnar, Erika. "Characterization of the genetic basis in two cases of abetalipoproteinemia reveals two novel mutations." Thesis, Linköping University, Department of Physics, Chemistry and Biology, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-58620.

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BACKGROUND: Abetalipoproteinemia (ABL) is a rare autosomal recessive disorder caused by mutations in the gene coding for microsomal triglyceride transfer protein (MTTP).

AIM: To characterize the genetic basis of ABL in two unrelated patients.

RESULTS: In the first patient, the substitution c.1911C>T in exon 12 of the MTTP gene, resulting in the protein substitution p.P552L, was discovered using mutation screening. The parents are heterozygous and the proband is a homozygous carrier of this substitution. Using restriction fragment length polymorphism (RFLP), 100 control subjects were analyzed and none carried the substitution indicating that it is a novel MTTP mutation. Sequencing of the other ABL patient showed that the proband carried a homozygous single base insertion, at position  c.2342IVS16+2-3insT, located at the donor splice-site of intron 16 resulting in skipping of exon 16 and truncation of the protein. The proband's mother is heterozygous for the insertion while the father does not carry the insertion. Multiplex ligation-dependent probe amplification (MLPA) did not identify any deletion encompassing exon 16 in the proband, father or mother. Nonpaternity was excluded using polymorphic markers from several chromosomes. Haplotype analysis using markers spanning chromosome 4 revealed  heterodisomy (two homologous chromosomes) of 4p and the distal part of 4q, and isodisomy (duplication of one chromosome) of 4q12-4q26.

CONCLUSION: These data show that the cause of ABL in one of the patients is a missense mutation, p.P552L, while the cause of ABL in the other patient is due to uniparental disomy, probably resulting from non-disjunstion in meiosis I.

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Benavides, Edgar. "Evolution in Neotropical Herpetofauna: Species Boundaries in High Andean Frogs and Evolutionary Genetics in the Lava Lizard Genus Microlophus (Squamata: tropiduridae): A History of Colonization and Dispersal." Diss., CLICK HERE for online access, 2006. http://contentdm.lib.byu.edu/ETD/image/etd1652.pdf.

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Saunders, Elizabeth. "p53 mutational analysis in laryngeal squamous cell carcinoma, results of full-length gene sequencing." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape7/PQDD_0004/MQ45521.pdf.

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Al-Moyed, Hanan [Verfasser], Ellen [Akademischer Betreuer] Reisinger, Ellen [Gutachter] Reisinger, Nils [Gutachter] Brose, Sebastian [Gutachter] Kügler, Silvio [Gutachter] Rizzoli, Thomas [Gutachter] Dresbach, and Sven [Gutachter] Thoms. "Dual-AAV mediated transfer of full-length otoferlin cDNA into auditory inner hair cells and the effects of different mutations in the OTOF gene on the protein levels and cellular distribution of otoferlin in auditory inner hair cells / Hanan Al-Moyed ; Gutachter: Ellen Reisinger, Nils Brose, Sebastian Kügler, Silvio Rizzoli, Thomas Dresbach, Sven Thoms ; Betreuer: Ellen Reisinger." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2019. http://d-nb.info/1185757546/34.

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Bonnet, Celine. "Différentiation cellulaire, régulation des cellules souches et impact des mutations : une approche probabiliste." Thesis, Institut polytechnique de Paris, 2020. http://www.theses.fr/2020IPPAX016.

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Cette thèse porte sur la compréhension des mécanismes de différenciation cellulaire des cellules souches permettant la production des globules rouges (mécanisme appelé érythropoïèse). Nous avons élaboré différents modèles mathématiques permettant une compréhension à différents niveaux. Dans un premier temps, nous avons construit et calibré un modèle à 8 équations différentielles ordinaires pour décrire la dynamique de 6 populations de cellules en érythropoïèse de repos et de stress. L’étude de données expérimentales in vivo, recueillies par nos collaborateurs Stéphane Giraudier (hématologue) et Evelyne Lauret (INSERM), a montré la nécessité d’ajouter deux équations pour modéliser les régulations érythropoïètiques. La calibration du modèle a été effectuée à l’aide des données biologiques et d’un algorithme d’optimisation stochastique appelé CMA-ES. Ce modèle nous a permis de mettre en lumière l’importance de la capacité d’auto-renouvellement des cellules érythropoïètiques dans la production des globules rouges. L’élaboration d’un modèle probabiliste de dimension 3 nous a ensuite permis de comprendre les conséquences dynamiques de cette capacité sur la production des globules rouges. L’étude de ce modèle a nécessité des changements d’échelles en taille et en temps révélant un système dit lent/rapide. À l’aide de méthodes dites de moyennisation nous avons décrit l’approximation en grande population du nombre de cellules de chaque type. Nous avons également quantifié mathématiquement les grandes fluctuations biologiquement observées au niveau du nombre de globules rouges. Nous avons finalement construit un modèle pour comprendre l’influence des longues phases d’inactivité, connues, des cellules souches mutantes dans la production des globules rouges. Les cellules souches mutantes, en faible nombre dans l’organisme comparé aux cellules saines, basculent aléatoirement d’un état actif à un état inactif. Les différences d’échelle de taille entre les populations de cellules, nous a conduit à étudier la dynamique d’un processus de Markov déterministe par morceaux de dimension 4. Nous avons montré l’existence d’une unique probabilité invariante vers laquelle le processus converge en variation totale, et identifié cette limite
This thesis focuses on understanding the mechanisms of stem cell differentiation leading to the production of red blood cells (a mechanism called erythropoiesis). To this end, we have developed different mathematical modelling leading to an understanding at different levels. Firstly, we have built and calibrated a model with 8 ordinary differential equations to describe the dynamics of 6 populations of cells in steady-state and stress erythropoiesis. The study of in vivo experimental data, realized by our collaborators St´ephane Giraudier (hematologist) and Evelyne Lauret (INSERM), showed the need of two equations to model erythropoiesis regulations. Modeling calibration was performed using biological data and a stochastic optimization algorithm called CMA-ES. This model highlighted the importance of the self-renewal capacity of the erythropoietic cells in the production of red blood cells. The development of a 3-dimensional probabilistic model then allowed us to understand the dynamic consequences of this capacity on the production of red blood cells. The study of this model required changes of scale in size and time revealing a so-called slow/fast system. Using averaging methods, we described the large population approximation of the number of each cell type. We have also mathematically quantified the large fluctuations in the number of red blood cells, biologically observed. Finally, we constructed a model to understand the influence of long periods of inactivity of mutant stem cells in the production of red blood cells. Mutant stem cells, which are in low numbers in the organism compared to healthy cells, randomly switch between an active and an inactive state. The different size scale between the cell populations led us to study the dynamics of a 4-dimensional piecewise deterministic Markov process. We showed the existence of a unique invariant probability measure towards which the process converges in total variation, and we identified this limits
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GARCIA, LUIS. "Implication du canal ca#2#+ lent dans le couplage excitation-contraction du muscle squelettique : etude d'une mutation murine spontannee affectant ce couplage." Paris 7, 1989. http://www.theses.fr/1989PA077057.

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Etude des relations spatio-temporelles entre l'expression des canaux ca#2#+ (ontogenese et localisation) et la morphogenese des triades au cours de la myogenese in vitro. Analyse comparative des proprietes d'inactivation du canal ca#2#+ et du couplage excitation-contraction au cours de la phase de declenchement du couplage
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BOULLIOU, ANNIE. "Etude des copies virales endogenes, type alv, des poulets de chair. Recherche du mecanisme moleculaire de la mutation emplumement lent et de son lien au provirus ev-21." Rennes 1, 1991. http://www.theses.fr/1991REN10048.

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Les techniques rflp ont permis de differencier les copies virales endogenes, relatives aux retrovirus alv, presentes dans quatre lignees de poulets de chair. La structure du genome de ces provirus a ete etudiee pour delimiter d'eventuelles deletions. Ces souches se caracterisent par un nombre de provirus par animal beaucoup plus important que les poulets leghorn. Parmi les ev-b caracterises, nous avons reconnu ev-1, ev-6 et ev-21 deja recenses chez la leghorn. Ev-21 a ete retrouve chez tous les poulets k etudies, mais aussi chez les poulets a emplumement rapide k#+ de ponte. L'utilisation de la sonde ev-2lint a permis de caracteriser les deux loci pour ce provirus, occupe et inoccupe, et de demontrer leurs localisations sur le chromosome z. Les poulets k#+ ne possedent que l'un des deux loci alors que les k ont au moins un chromosome z porteur d'un locus occupe et d'un locus inoccupe en position cis. La reversion phenotypique k---k#+ s'accompagne de la perte d'un des deux loci. L'etude de la region d'insertion ev-21 chez d'autres vertebres, et en particulier des volailles susceptibles de presenter la mutation k a permis de relativiser l'importance du provirus dans cette mutation. Nous sommes parvenus a mettre en evidence, par la sonde ev-2lint, un arnm chez les embryons, mais la difference entre les deux phenotypes n'est pas etablie
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Léveillard, Thierry. "Le polymorphisme des gènes de l'inter-alpha-trypsine inhibiteur : recherche d'association génétique avec l'emphysème pulmonaire." Rouen, 1989. http://www.theses.fr/1989ROUES015.

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RFLP des gènes de l'inhibiteur de la trypsine inter alpha chez l'homme, déterminisme génétique et fréquence allélique de ces marqueurs dans une population de référence et dans une population constituée d'individus non déficitaires en alpha-1-antitrypsine souffrant d'emphysème pulmonaire
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Deguti, Marta Mitiko. ""Doença de Wilson: aspectos demográficos e fenotípicos relacionados ao genótipo ATP7B e estudo do haplótipo em portadores da mutação L708P"." Universidade de São Paulo, 2004. http://www.teses.usp.br/teses/disponiveis/5/5147/tde-02052006-093857/.

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A doença de Wilson é um distúrbio da excreção biliar de cobre devido a um defeito na proteína ATP7B. Em caráter pioneiro na América do Sul, seqüenciou-se o gene ATP7B em 60 pacientes brasileiros pertencentes a 46 famílias; os resultados foram relacionados com aspectos demográficos e fenotípicos. Detectaram-se 25 mutações, 12 das quais novas. A 3402delC (34,8%) e a L708P (14,1%) ocorreu em 58,3% das famílias de São Paulo e em 44,4% das de Minas Gerais, respectivamente. As substituições novas, pesquisadas por RFLP ou PCR alelo-específica, não ocorreram em 60 indivíduos controle; portanto, não são polimorfismos comuns. O estudo comparativo de haplótipos dos portadores da L708P da coorte atual e de Gran Canaria sugeriu um efeito-fundador comum para ambos os grupos. O fenótipo variou amplamente para genótipos idênticos
ATP7B protein. As the first study of its kind in South America, the ATP7B gene was sequenced and the results were related to demographic and phenotypic aspects of 60 Brazilian patients, from 46 distinct families. Twenty-five mutations were detected, 12 of which are novel. The 3402delC (34.8%) and the L708P (14.1%) occurred in 58.3% of the families from Sao Paulo and in 44.4% of those from Minas Gerais, respectively. The novel substitutions were shown not to be common polymorphisms by RFLP or allele-specific PCR studies performed in 60 control subjects. Haplotype analysis comparing carriers of the L708P from this cohort study with patients from Gran Canary suggests the same founder-effect for both groups. Phenotype varied widely for identic genotypes.
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Books on the topic "Length mutations"

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Saunders, Elizabeth. p53 mutational analysis in laryngeal squamous cell carcinoma: Results of full-length gene sequencing. [Toronto: University of Toronto, Faculty of Dentistry], 1999.

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Hipkins, Valerie D. Repeated sequences associated with inversions and length mutations in the chloroplast genomes of Pseudotsuga and Pinus. 1993.

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Cazeneuve, Cécile, and Alexandra Durr. Genetic and Molecular Studies. Oxford University Press, 2014. http://dx.doi.org/10.1093/med/9780199929146.003.0006.

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Huntington’s disease (HD) is a rare inherited neurologic disorder due to a single mutational mechanism in a large gene (HTT). The mutation is an abnormal CAG repeat expansion, which is translated to a polyglutamine stretch in the huntingtin protein. The growing field of repeat expansion disorders benefits greatly from the lessons learned from the role of the CAG repeat expansion in HD and its resulting phenotype–genotype correlations. The molecular diagnosis can be difficult, and there are some pitfalls for accurate sizing of the CAG repeat, especially in juvenile HD and for intermediate alleles. Correlation between CAG length and age of onset accounts for up to 72% of the variance in different populations, but the search for genes modifying age of onset or progression of HD is still ongoing.
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Book chapters on the topic "Length mutations"

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Schnittger, S., C. Schoch, M. Dugas, W. Kern, P. Staib, Ch Wuchter, Ch M. Sauerland, et al. "FLT3 Length Mutations and MLL-Duplications in AML: Correlation to Cytogenetics, FAB-Subtype,and Prognosis." In Haematology and Blood Transfusion Hämatologie und Bluttransfusion, 301–5. Berlin, Heidelberg: Springer Berlin Heidelberg, 2003. http://dx.doi.org/10.1007/978-3-642-59358-1_48.

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Humphries, S., A. Dunning, Chun-Fang Xu, and P. Talmud. "Genetic Control of Plasma Lipid, Lipoprotein and Apolipoprotein Levels: From Restriction Fragment Length Polymorphisms to Specific Mutations." In Cellular and Molecular Biology of Atherosclerosis, 121–33. London: Springer London, 1992. http://dx.doi.org/10.1007/978-1-4471-1909-8_11.

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Minvielle-Sebastia, L., A. Petitjean, B. Winsor, N. Bonneaud, and F. Lacroute. "Mutations Involved in mRNA Stability and in the Length of their Poly(A) Tails in the Yeast Saccharomyces cerevisiae." In Post-Transcriptional Control of Gene Expression, 55–64. Berlin, Heidelberg: Springer Berlin Heidelberg, 1990. http://dx.doi.org/10.1007/978-3-642-75139-4_6.

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Dammai, Vincent. "A Rapid and Versatile PCR-Based Site-Directed Mutagenesis Protocol for Generation of Mutations Along the Entire Length of a Cloned cDNA." In Methods in Molecular Biology, 111–26. Totowa, NJ: Humana Press, 2010. http://dx.doi.org/10.1007/978-1-60761-652-8_8.

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Van Ryt, Saskia, Marcus Gallagher, and Ian Wood. "A Novel Mutation Operator for Variable Length Algorithms." In AI 2020: Advances in Artificial Intelligence, 176–88. Cham: Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-030-64984-5_14.

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Koshlan, Tatiana, and Kirill Kulikov. "Mathematical Modelling of the Interaction of BH3-Peptides with Full-Length Proteins, and Account of the Influence of Point Mutations on the Stability of the Formed Biological Complex on the Example of the Bcl-2 Family Proteins." In Mathematical Modeling of Protein Complexes, 291–308. Cham: Springer International Publishing, 2018. http://dx.doi.org/10.1007/978-3-319-98304-2_7.

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Cilia, Nicole Dalia, Claudio De Stefano, and Francesco Fontanella. "Novel Mutation Operators of a Variable-Length Representation for EC-Based Feature Selection in High-Dimensional Data." In Intelligent Computing Theories and Application, 53–63. Cham: Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-030-60799-9_5.

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Boyko, Alex, and Igor Kovalchuk. "Analysis of Mutation/Rearrangement Frequencies and Methylation Patterns at a Given DNA Locus Using Restriction Fragment Length Polymorphism." In Plant Epigenetics, 49–62. Totowa, NJ: Humana Press, 2010. http://dx.doi.org/10.1007/978-1-60761-646-7_6.

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Jernström, H., O. Johannsson, Å. Borg, and H. Olsson. "No Significant Difference in Age at Menarche, Menstrual Cycle Length, Age at First Full-Term Pregnancy, and Nulliparity Among BRCA1 Mutation Carriers Compared with Their Unaffected Relatives." In Hormonal Carcinogenesis III, 413–17. New York, NY: Springer New York, 2001. http://dx.doi.org/10.1007/978-1-4612-2092-3_41.

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Ahmed, Omar. "Genre Mutations." In RoboCop, 19–44. Liverpool University Press, 2018. http://dx.doi.org/10.3828/liverpool/9781911325253.003.0003.

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This chapter discusses Paul Verhoeven's RoboCop (1987) as a Western. Though the film's hybridity has been mentioned especially in regards to science fiction's interrelatedness with horror, and in the intertextual nods to Shane (1953), it has not been explored at length to sufficiently argue for iconographic slippages that account for the salience of the Western. The chapter's purpose is to widen the possibilities of looking intimately at the way iconographic details can create genre dissonance, what is known as ‘vraisemblance’. Reframing genre readings means retracing the intersections with the horror and science fiction. This includes accommodating for developments such as the science-fiction Western, a sub-genre that has veered from innovation to derision yet continues to elicit new rejoinders. The chapter then offers a consideration of Western themes, notably the savage, the massacre, and revenge, which intersects with the horror genre.
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Conference papers on the topic "Length mutations"

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Gautieri, Alfonso, Sebastien Uzel, Simone Vesentini, Alberto Redaelli, and Markus J. Buehler. "Osteogenesis Imperfecta: Molecular and Mesoscale Disease Mechanisms." In ASME 2009 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2009. http://dx.doi.org/10.1115/sbc2009-204530.

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Osteogenesis Imperfecta (OI) is a genetic disorder in collagen characterized by mechanically weakened tendon and fragile bones that affects more than 1 in 10,000 individuals. Even though many studies have attempted to associate specific mutation types with phenotypic severity, the mechanisms by which a single point mutation influences the mechanical behavior of tissues at multiple length-scales remain unknown. Here we show by a hierarchy of full atomistic and mesoscale simulation that OI mutations severely compromise the mechanical properties of collagenous tissues at multiple scales, from single molecules to collagen fibrils.
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Rachakonda, Sivaramakirishna, Barbara Heidenreich, Eduardo Nagore, and Rajiv Kumar. "Abstract 3408: Telomere length and TERT promoter mutations in cutaneous melanoma." In Proceedings: AACR Annual Meeting 2017; April 1-5, 2017; Washington, DC. American Association for Cancer Research, 2017. http://dx.doi.org/10.1158/1538-7445.am2017-3408.

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Tang, Alison. "Abstract 3443: Full-length characterization of transcript isoforms to investigate cancer-associated mutations." In Proceedings: AACR Annual Meeting 2018; April 14-18, 2018; Chicago, IL. American Association for Cancer Research, 2018. http://dx.doi.org/10.1158/1538-7445.am2018-3443.

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Hirochika, H., A. Miyao, M. Yamazaki, A. Takahashi, G. K. Agrawal, C. Cheng, Y. Yamashita, et al. "Tissue culture–induced mutations and overexpression of full-length cDNAs as a tool for functional analysis of rice genes." In Proceedings of the Fifth International Rice Genetics Symposium. World Scientific Publishing Company, 2007. http://dx.doi.org/10.1142/9789812708816_0006.

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Geddes, V. A., G. V. Louie, G. D. Brayer, and R. T. A. MacGillivray. "MOLECULAR BASIS OF HEMOPHILIA B: IDENTIFICATION OF THE DEFECT IN FACTOR IX VANCOUVER." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643872.

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Factor IX Vancouver (fIX-V) is the cause of a moderate form of hemophilia B. An individual presenting with this disorder had 2.6% of normal procoagulant activity in his plasma but had 62% of the normal factor IX antigen level. Specific antibodies showed that fIX-V contains epitopes for both the heavy and light chains of factor IXa. To identify the defect involved, DNA was isolated from the lymphocytes of the male hemophiliac. Southern blot analysis using a full-length factor IX cDNA as a hybridization probe showed no gross differences between the fIX-V gene and the normal factor IX gene. The DNA from the hemophiliac was then partially digested with Sau3A and the resulting fragments (10-20kbp in size) were ligated into the BamHI site of λEMBL3. The DNA was then packaged into phage particles in vitro, and the recombinant phage were screened with the factor IX cDNA as a probe. Eight phage were isolated that contained overlapping DNA covering the complete gene for fIX-V. DNA sequence analysis of the protein-encoding regions, the intron/exon junctions and 5'-and 3'-flanking sequences revealed a single nucleotide change from the normal factor IX gene. The codon for amino acid 397 was changed from ATA (lie) to ACA (Thr). This mutation is in the catalytic domain of factor IXa and is novel amongst those hemophilia B mutations reported to date. Based on the known three dimensional structures of the pancreatic serine proteases, trypsin, elastase and chymotrypsin, models have been constructed for the structures of the catalytic domains of both the normal and Thr-397 mutant of factor IXa. These results suggest that the Thr-397 mutation may alter the conformation of the substrate binding region in the active site of factor IXa Vancouver through the formation of a hydrogen bond between the hydroxyl group of the Thr-397 side chain and the main chain carbonyl group of Trp-385. The postulated conformational change would lead to reduced binding affinity for the factor IXa substrate resulting in a reduction in the catalytic activity of fIXa-Vancouver.Supported in part by grants from the Medical Research Council of Canada (to GDB and RTAM).
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Yan, Terry, Jason Yobby, and Ravindra Vundavilli. "Optimal Design of IC Engine Cooling Fins by Using Genetic Algorithm." In ASME 2014 International Mechanical Engineering Congress and Exposition. American Society of Mechanical Engineers, 2014. http://dx.doi.org/10.1115/imece2014-39446.

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The analysis for optimal design of an air-cooled internal combustion engine cooling fin array by using genetic algorithms (GA) is presented in this study. Genetic Algorithms are robust, stochastic search techniques which are also used for optimizing highly complex problems. In this study, the fin array is of the traditional circular fin type, which is subject to ambient convective heat transfer. The parameters (degrees of freedom) selected for the analysis include the cylinder wall thickness-to-radius ratio, fin thickness, fin length, the number of fins, and the local heat transfer coefficient. By using a single objective GA procedure, the heat transfer through the fin arrays is set as the objective function to be optimized with each parameter varied within the physical ranges. Proper population size is selected and the mutations, cross-over and selection are conducted in the GA procedure to arrive at the optimal set of parameters after a certain number of generations. The GA proves to be an effective optimization method in the thermal system component designs when the number of independent variables is large.
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Giannelli, B. F. "MOLECULAR GENETICS OF HAEMOPHILIA." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643981.

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Haemophilia B, an X-linked recessive disease with an incidence of 1/30,000 newborn males, is due to defects in the gene for coagulation factor IX, which is on the long am of the X chromosome at band Xq27.1. This gene consists of approximately 34 Kb and contains 8 exons which specify a mRtfc of 2803 residues coding for a protein of 415 aa preceded by a prepro signal peptide of 46 aa. Coripanson of the functional domains of the factor IX protein with the exon structure of the gene supports the exon/protein domain hypothesis of gene evolution. The factor IX gene seems to be formed by a number of functionally and evolutionally independent modules. The signal peptide and the gla (γcarboxy-glutamic) region encoded in the first three exons are homologous to those of factor X, protein C and prothrombin. Thevfourth and fifth exons which code for the connecting peptide are homologous to one another and to the epidermal growth factor, a module that has been used in the construction of a great variety of proteins including different members of the coagulation and fibrinolytic pathways. The sixth exon encodes the activation peptide region, while the catalytic region of factor IX is coded by the seventh and eighth exon. This is at variance with other serine protease genes that have different exons for the segments containing the cardinal ami no-acids of the active centre (histidine, aspartic acid and serine).Natural selection acts against detrimental mutations of the factor IX gene and at each generation a proportion of haemophilia B genes is eliminated, as a significant number of patients does not reproduce. There appears to be no selective advantage to the heterozygote and therefore haemophilia B is maintained in the population by new mutations. Consequently, a significant proportion of patients should be born to non-carrier mothers, and unrelated patients should carry different gene defects, as recently verified by detailed analysis of individual haemophilia B genes.The defects of factor IX described so far comprise both point mutations and gene deletions. The latter affect either part or the whole of the gene and are often associated with the development of antibodies against therapeutically adninistered factor IX (the inhibitor complication). Since gene deletions may result in the complete absenceof factor IX synthesis or in the production of an extremely abnormal product, it has been suggested that mutationspreventing the synthesis of a factor IX gene product capable of inducing immune tolerance to normal factor IX is important in predisposing to the inhibitor complication.Among the point mutations described so far, those affecting the signal peptide are of particular interest. Substitutions of the arginine at positions -4 and -1 cause failure of propeptide cleavage. Thus they indicate that the propeptide consists of 18 aa an(lthat lts excision is necessary for factor IX function. It appears also that the propeptide contains a signal for γcarboxylation which has been conserved during the evolution of different γcarboxylated proteins.In spite of coagulant treatment, haemophilia B is a serious disease and one for which genetic counselling is required. Paramount for this is the detection of carriers and the diagnosis ofaffected male fetuses. DNA probes derived from the cloned factor IX gene have been used for this purpose. Carrier and first or second trimester prenatal diagnoses have been done using factors IX gene markers to follow the transmission of haemophilia B genes. Six sequence variations causing restriction fragment length polymorphisms (RFLP) in the factor IX gene have been detected and used as markers for such indirect diagnoses The efficiency of the above markers is reduced by linkage disequilibrium but, nevertheless, they offer definite carrier and nremtal diagnoses in 75-80% of the relatives of familial cases of haemophilia B.The indirect detection of gene defects is of modest help in the counselling of individuals from the families of isolated patients, but new methods for the direct detection of gene mutations promise better results in such families and also the attainment of % diagnostic success in relatives of familial cases.Finally the successful expression of recombinant factor IX genes in tissue culture and transgenic mammals raises hopes of therapeutic advances.
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Pannekok, H., A. J. Van Zonneveid, C. J. M. de vries, M. E. MacDonald, H. Veerman, and F. Blasi. "FUNCTIONAL PROPERTIES OF DELETION-MUTANTS OF TISSUE-TYPE PLASMINOGEN ACTIVATOR." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643724.

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Over the past twenty-five years, genetic methods have generated a wealth of information on the regulation and the structure-function relationship of bacterial genes.These methods are based on the introduction of random mutations in a gene to alter its function. Subsequently, genetic techniques cure applied to localize the mutation, while the nature of the impairedfunction could be determined using biochemical methods. Classic examples of this approach is now considered to be the elucidation of the structure and function of genes, constituting the Escherichia coli lactose (lac) and tryptophan (trp) operons,and the detailed establishment of the structure and function of the repressor (lacl) of the lac operon. Recombinant DNA techniques and the development of appropriate expression systems have provided the means both to study structure and functionof eukaryotic (glyco-) proteins and to create defined mutations with a predestinedposition. The rationale for the construction of mutant genes should preferentiallyrely on detailed knowledge of the three-dimensional structure of the gene product.Elegant examples are the application of in vitro mutagenesis techniques to substitute amino-acid residues near the catalytic centre of subtilisin, a serine proteasefrom Bacillus species and to substituteanamino acid in the reactive site (i.e. Pi residue; methionine) of α-antitrypsin, a serine protease inhibitor. Such substitutions have resulted into mutant proteins which are less susceptible to oxidation and, in some cases, into mutant proteins with a higher specific activity than the wild-type protein.If no data are available on the ternary structure of a protein, other strategies have to be developed to construct intelligent mutants to study the relation between the structure and the function of a eukaryotic protein. At least for a number of gene families, the gene structure is thought to be created by "exon shuffling", an evolutionary recombinational process to insert an exon or a set of exons which specify an additional structural and/or functional domain into a pre-existing gene. Both the structure of the tissue-type plasminogen activator protein(t-PA) and the t-PA gene suggest that this gene has evolved as a result of exon shuffling. As put forward by Gilbert (Science 228 (1985) 823), the "acid test"to prove the validity of the exon shuffling theory is either to delete, insert or to substitute exon(s) (i.e. in the corresponding cDNA) and toassay the properties of the mutant proteins to demonstrate that an exon or a set of adjacent exons encode (s) an autonomousfunction. Indeed, by the construction of specific deletions in full-length t-PA cDNA and expression of mutant proteins intissue-culture cells, we have shown by this approach that exon 2 of thet-PA gene encodes the function required forsecretion, exon 4 encodes the "finger" domain involved in fibrin binding(presumably on undegraded fibrin) and the set of exons 8 and 9 specifies kringle 2, containing a lysine-binding sit(LBS) which interacts with carboxy-terminal lysines, generated in fibrin after plasmic digestion. Exons 10 through 14 encode the carboxy-ter-minal light chain of t-PA and harbor the catalytic centre of the molecule and represents the predominant "target site" for the fast-acting endothelial plasminogen activator inhibitor (PAI-1).As a follow-up of this genetic approach to construct deletion mutants of t-PA, we also created substitution mutants of t-PA. Different mutants were constructed to substitute cDNA encoding thelight chain of t-PA by cDNA encoding the B-chain of urokinase (u-PA), in order to demonstrate that autonomous structural and functional domains of eitherone of the separate molecules are able toexert their intrinsic properties in a different context (C.J.M. de Vries et al., this volume). The possibilities and the limitations of this approach to study the structure and the function of t-PA and of other components of the fibrinolytic process will be outlined.
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Wang, Bingwen, and Erik K. Antonsson. "Hierarchical Modularity: Decomposition of Function Structures With the Minimal Description Length Principle." In ASME 2005 International Design Engineering Technical Conferences and Computers and Information in Engineering Conference. ASMEDC, 2005. http://dx.doi.org/10.1115/detc2005-85173.

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In engineering design and analysis, complex systems often need to be decomposed into a hierarchical combination of different simple subsystems. It’s necessary to provide formal, computable methods to hierarchically decompose complex structures. Since graph structures are commonly used as modeling methods in engineering practice, this paper presents a method to hierarchically decompose graph structures. The Minimal Description Length (MDL) principle is introduced as a measure to compare different decompositions. The best hierarchical decomposition is searched by evolutionary computation methods with newly defined crossover and mutation operators of tree structures. The results on abstract graph without attributes and a real function structure show that the technique is promising.
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Cathabard, Stephan, Per Kristian Lehre, and Xin Yao. "Non-uniform mutation rates for problems with unknown solution lengths." In the 11th workshop proceedings. New York, New York, USA: ACM Press, 2011. http://dx.doi.org/10.1145/1967654.1967670.

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Reports on the topic "Length mutations"

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Kline, Margaret C., Carolyn R. Steffen, and David L. Duewer. Certification and Extension of the Period of Validity for Standard Reference Material® 2393 CAG Repeat Length Mutation in Huntington’s Disease. National Institute of Standards and Technology, October 2020. http://dx.doi.org/10.6028/nist.sp.260-203.

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