tailieunhanh - Báo cáo sinh học: "Pitfalls in the phylogenomic evaluation of human disease-causing mutations"

Tuyển tập các báo cáo nghiên cứu về sinh học được đăng trên tạp chí sinh học Journal of Biology đề tài:Pitfalls in the phylogenomic evaluation of human disease-causing mutations. | Journal of Biology BioMed Central Minireview Pitfalls in the phylogenomic evaluation of human disease-causing mutations Andrew OM Wilkie Address Weatherall Institute of Molecular Medicine University of Oxford John Radcliffe Hospital Headington Oxford OX3 9DS UK. Email awilkie@ Published 24 March 2009 Journal of Biology 2009 8 26 doi jbiol127 The electronic version of this article is the complete one and can be found online at http content 8 3 26 2009 BioMed Central Ltd Abstract A detailed sequence comparison of the MSX homeobox family sheds light on its evolution and identifies new conserved motifs. But in the absence of corroborative genetic data phylo-genomics alone can provide only limited insights into the pathogenicity of heterozygous missense substitutions in human genes. The explosion in genome sequencing provides a rich resource for reconstructing the evolutionary origins of gene families. One proposed application for such phylogenomic information is to identify highly conserved sequences in human proteins suspected of being associated with disease and to use this information to identify sequence variants in these regions as potential disease-causing mutations. A recent example of this approach is a study by Finnerty et al. of the MSX homeobox family published in BMC Evolutionary Biology 1 . MSX is of particular interest because it represents one of the most ancient families of animal homeodomain proteins and mutations in both paralogous human genes MSX1 and MSX2 have been associated with craniofacial disorders 1 2 . The work by Finnerty et al. 1 which focuses on the MSX1 sequence changes provides a useful case study in the context of current initiatives to generate large amounts of genomic sequence data from complex diseases. These will yield thousands of rare sequence variants causing headaches for interpretation of the pathogenicity of individual sequence changes. So how successful has the analysis of MSX sequences .