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Biomedical subjects

R N Curnow

Publications and source records attributed to R N Curnow.

At least 37 records · Page 2Linked to original sources
PubMed1990

Tests for the statistical significance of protein sequence similarities in data-bank searches.

A suite of tests to evaluate the statistical significance of protein sequence similarities is developed for use in data bank searches. The tests are based on the Wilbur-Lipman word-search algorithm, and take into account the sequence lengths and compositions, and optionally the weighting of amino acid matches. The method is extended to allow for the existence of a sequence insertion/deletion within the region of similarity. The accuracy of statistical distributions underlying the tests is validated using randomly generated sequences and real sequences selected at random from the data banks. A computer program to perform the tests is briefly described.

Algorithms↗
PubMed1989

A test for the statistical significance of DNA sequence similarities for application in databank searches.

A method is developed, based on word-searching, which provides a rapid test for the statistical significance of DNA sequence similarities for use in databank searching. The method makes allowance for the lengths and dinucleotide compositions of the sequences being compared. A way is also described to calculate the power of the test, i.e. the probability of detecting a given similarity as being statistically significant. The effects on the power of the test of the scoring method, word length, sequence length, and sequence composition are examined. A novel scoring method is shown to be superior to the method currently used in most word-searching algorithms.

Base Sequence↗
PubMed1988

The use of Markov chain models in studying the evolution of the proteins.

In a recent paper Giulio & Caldararo (1987) used a Markov chain model to study the evolution of proteins. Unfortunately, their use of a first-order Markov chain model at the amino acid level is incorrect. The model has to be applied at the codon level [Jorre & Curnow (1975a)] followed by amalgamation of the codon states corresponding to each amino acid and of the three codons specifying termination. The model is correctly applied in this paper. The results obtained do not differ substantially from those obtained by Giulio & Caldararo (1987). The interpretation of the results as supporting the neutralist view of protein evolution is criticized.

Amino Acids↗
PubMed1987

Origin of noncoding DNA sequences: molecular fossils of genome evolution.

The total amount of noncoding sequences on chromosomes of contemporary organisms varies significantly from species to species. We propose a hypothesis for the origin of these noncoding sequences that assumes that (i) an approximately equal to 0.55-kilobase (kb)-long reading frame composed the primordial gene and (ii) a 20-kb-long single-stranded polynucleotide is the longest molecule (as a genome) that was polymerized at random and without a specific template in the primordial soup/cell. The statistical distribution of stop codons allows examination of the probability of generating reading frames of approximately equal to 0.55 kb in this primordial polynucleotide. This analysis reveals that with three stop codons, a run of at least 0.55-kb equivalent length of nonstop codons would occur in 4.6% of 20-kb-long polynucleotide molecules. We attempt to estimate the total amount of noncoding sequences that would be present on the chromosomes of contemporary species assuming that present-day chromosomes retain the prototype primordial genome structure. Theoretical estimates thus obtained for most eukaryotes do not differ significantly from those reported for these specific organisms, with only a few exceptions. Furthermore, analysis of possible stop-codon distributions suggests that life on earth would not exist, at least in its present form, had two or four stop codons been selected early in evolution.

Animals↗
PubMed1979

A two-locus model for the inheritance of a familial disease.

A model for the inheritance of a disease involving genes at just two linked loci is presented and discussed. One of the two pairs of opposite double homozygotes is assumed to lead to the disease and death. The other genotypes are assumed to be less fit than the double heterozygote. The cause of this reduced fitness may or may not be due to the disease. Conditions for the existence of a stable equilibrium are presented. The model has a sound biological basis and could be used to explain a wide range of disease frequencies and patterns of inheritance. Mutation is not required to explain why the disease persists in the population. Recurrence risks for sibs and twin concordance rates are derived and the consequences of the relaxation of selection against those with the disease are predicted. The effects of a selection model of the kind described on the amount of linkage disequilibrium in the population and on the estimation of the frequency of recombination are discussed.

Chromosome Mapping↗
PubMed1978

On effects of relaxed selection in familial disorders.

Theoretical predictions are made of the effect of improved treatments, with consequent increase in fertility of affected individuals, on the frequency of familial disorders. Multifactorial inheritance and some two-locus models are considered. (Changes for simple Mendelian disorders have been estimated previously by many authors.) It is estimated that, with two-locus or multifactorial models, an increase in frequency per generation of not more than a few per cent of the frequency of a disorder may be expected. The greatest increase will be in the first generation following introduction of the new treatment.

Gene Frequency↗