Extension of Phenotype Associated with Structural Mutations in Type I Collagen: Siblings with Juvenile Osteoporosis Have an α2(I)Gly436 → Arg Substitution
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Abstract Mutations in the type I collagen genes have been identified as the cause of all four types of osteogenesis imperfecta (OI). We now report a mutation that extends the phenotype associated with structural abnormalities in type I collagen. Two siblings presented with a history of back pain and were diagnosed with juvenile osteoporosis, based on clinical and radiological examination. Radiographs showed decreased lumbar bone density and multiple compression fractures throughout the thoracic and lumbar spines of both patients. One child has moderate short stature and mild neurosensory hearing loss. However, neither child has incurred the long bone fractures characteristic of OI. Protein studies demonstrated electrophoretically abnormal type I collagen in samples from both children. Enzymatic cleavage of RNA:RNA hybrids identified a mismatch in type I collagen α2 (COL1A2) mRNA. DNA sequencing of COL1A2 cDNA subclones defined the mismatch as a single-base mutation (1715G → A) in both children. This mutation predicts the substitution of arginine for glycine at position 436 (G436R) in the helical domain of the α2(I) chain. Analysis of genomic DNA identified the mutation in the asymptomatic father, who is presumably a germ-line mosaic carrier. The presence of the same heterozygous mutation in two siblings strongly suggests that the probands display the full phenotype. Taken together, the clinical, biochemical, and molecular findings of this study extend the phenotype associated with type I collagen mutations to cases with only spine manifestations and variable short stature into adolescence.Keywords:
Substitution (logic)
Amino acid substitution
Type I collagen
Due to the variable subjects and methods of solving problems in Higher Mathematics,substitution will not only flexibly develop the ways of problem solving,but also an effect of simplification.By reversing the examples in solving the problems of application,substitution,ways of incremental-substitution,tangle-substitution,double-substitution,unequal-substitution,ratio-substitution and so on,are discussed.
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Most of the existing approaches view amino acid substitution as a pairwise phenomenon. Most methods characterizes it using substitution matrices. Some methods focus on determination of substitution groups based on the theoretical properties satisfied by the substitution groups. Be it any method algorithms on these reliable techniques are required for actual determination of the amino acid substitutions. In this paper we provide an algorithmic approach for determination of amino acid substitution group.
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Abstract Suppose that amino acid or nucleotide data are available for a homologous gene in several species which diverged from a common ancestor at about the same time and that substitution rates between all pairs of species are calculated, correcting as necessary for multiple substitutions and for back and parallel substitutions. The variances and covariances of these corrected substitution rates are evaluated, and are used to construct a new test for uniformity (constancy of the molecular clock) and to find the best estimates of substitution rates in individual lineages with their standard errors. A substantial bias may arise if the effect of correcting the pairwise substitution rates is ignored.
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Methods for alignment of protein sequences typically measure similarity by using a substitution matrix with scores for all possible exchanges of one amino acid with another. The most widely used matrices are based on the Dayhoff model of evolutionary rates. Using a different approach, we have derived substitution matrices from about 2000 blocks of aligned sequence segments characterizing more than 500 groups of related proteins. This led to marked improvements in alignments and in searches using queries from each of the groups.
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Amino acid substitution
Similarity (geometry)
Protein evolution
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When we solve a maths problem,we should use the method of substitution to make the problem easier.It is the equivalent generation changes.Also it has three forms;triangle substitution,the radical substitution,overall substitution,and the equivalent generation substitution.
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Amino acid substitution
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The present work describes protrates, a program that estimates amino acid substitution matrices and among-site substitution rates based on their likelihood for a given tree topology and a dataset of aligned proteins. The issue of producing maximum likelihood (ML) rate matrices over protein data have been adressed under the framework of general-purpose unbiased substitution matrices [1, 9], since it’s believed that parsimony-estimated matrices can be systematically distorted and ignore backward and parallel substitutions which can affect branch lenghts of ML topologies [2, 4].
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Since first proposed in 2002, Bayesian substitution mappings have found less use than might have been expected in the field of molecular evolution. Here, I first create a sequence simulator capable of generating true substitution mappings for simulated data under any time-reversible model in order to facilitate study of substitution mappings. I then investigate the utility of substitution mappings for two applications: detection of coevolving residues and scoring of amino acid substitution radicality to test the predictions of the nearly neutral theory. I find that mappings perform poorly for coevolution detection, but using mappings to find the radicality of an average amino acid by scoring each observed substitution works well. Overall, substitution mappings look to be a potentially useful tool for some types of molecular evolution studies.
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Amino acid substitution
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Pfam_datasets.zip: Pfam training and test sets.
05_clades.zip: Training and test sets of five clades.
non_reversible_matrices.zip: Six time non-reversible matrices for Pfam, Bird, Insect, Mammal, Plant, and Yeast datasets.
pca script.zip: an R scrip and matrices to produce the PCA figure
05_clades.zip: Training and test sets of five clades.
non_reversible_matrices.zip: Six time non-reversible matrices for Pfam, Bird, Insect, Mammal, Plant, and Yeast datasets.
pca script.zip: an R scrip and matrices to produce the PCA figure
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Amino acid substitution
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The paper describes results of testing of "recognition ability" of different substitution matrices and various pseudo-potentials (taken from literature or designed by us) to recognize protein structures and produce the sequence-to-structure alignments. Numerical estimates of "identifying power" of various matrices and pseudo-potentials are obtained for different levels of similarity between amino acid sequences of spatially-similar proteins. It is shown that substitution matrices work much better than pseudo-potentials at a high level of similarity of sequences of spatially-similar proteins, but some pseudo-potentials overcome substitution matrices at a low level of sequence similarity.
Substitution (logic)
Similarity (geometry)
Sequence (biology)
Amino acid substitution
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