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Statistical methodology for assessing homology of intronic regions of genes
Authors:Deborah L. Hall  Karen Kafadar  Alvin M. Malkinson
Abstract:We consider the problem of statistically evaluating the similarity of DNA intronic regions of genes. Present algorithms are based on matching a sequence of interest with known DNA sequences in a gene bank and are designed primarily to assess homology among exonic regions of genes. Most research focuses on exonic regions because they have a clear biological significance, coding for proteins, and therefore tend to be more conserved in evolution than intronic regions. To investigate whether the intronic features of genes whose expression is highly sensitive to environmental perturbations differ from genes that have a more constant expression, a collection of oncogenes, tumor suppressor genes, and nonregulatory genes involved in energy metabolism are compared. An analysis of the features of these genes' intronic regions result in clustering by regulatory group. In addition, Billingsley's test for Markov structure (1961) suggests that 67% of the intronic regions in this collection of genes show evidence of nonrandom structure, indicating the possibility of a biological function for these regions. The result of Billingsley's test for homology is used as input to a clustering algorithm. The biological significance of this methodology lies in the identification of groups based on the intronic regions from genes of unknown function. With the advent of rapid sequencing techniques, there is a great need for statistical techniques to help identify the purpose of poorly understood portions of genes. These methods can be utilized to assess the functional group to which such a gene might possibly belong.
Keywords:Cluster analysis  homology  interrupted genes  introns  Markov processes  noncoding DNA  oncognes  sequence analysis  transition matrix
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