Survey of human mitochondrial diseases using new genomicproteomic tools 英文参考文献.docVIP

/2001/2/6/research/0021.1 Research Survey of human mitochondrial diseases using new genomic/proteomic tools Thomas N Plasterer*, Temple  Smith? and Scott C Mohr? Addresses: *BioMolecular Engineering Research Center and Department of Pharmacology, Boston University School of Medicine, 80 E Concord Street, Boston, MA 02118, USA. ?BioMolecular Engineering Research Center, Boston University College of Engineering, 36 Cummington Street, Boston, MA 02215, USA. ?BioMolecular Engineering Research Center and Department of Chemistry, Boston University, 590 Commonwealth Avenue, Boston, MA 02215, USA. Correspondence: Scott C Mohr. E-mail: mohr@ Published: 1 June 2001 Received: 8 February 2001 Revised: 3 April 2001 Accepted: 26 April 2001 GenomeBiology 2001, 2(6):research0021.1–0021.16 The electronic version of this article is the complete one and can be found online at /2001/2/6/research/0021 ? 2001 Plasterer et al., licensee BioMed Central Ltd (Print ISSN 1465-6906; Online ISSN 1465-6914) Abstract Background: We have constructed Bayesian prior-based, amino-acid sequence profiles for the complete yeast mitochondrial proteome and used them to develop methods for identifying and characterizing the context of protein mutations that give rise to human mitochondrial diseases. (Bayesian priors are conditional probabilities that allow the estimation of the likelihood of an event - such as an amino-acid substitution - on the basis of prior occurrences of similar events.) Because these profiles can assemble sets of taxonomically very diverse homologs, they enable identification of the structurally and/or functionally most critical sites in the proteins on the basis of the degree of sequence conservation. These profiles can also find distant homologs with determined three- dimensional structures that aid in the interpretation of effects of missense mutations. Results: This survey reports such an analysis for 15 missense mutations, one inserti