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An alignment-free method to find and visualise rearrangements between pairs of DNA sequences OPEN
"... Species evolution is indirectly registered in their genomic structure. The emergence and advances in sequencing technology provided a way to access genome information, namely to identify and study evolutionary macro-events, as well as chromosome alterations for clinical purposes. This paper describ ..."
Abstract
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Species evolution is indirectly registered in their genomic structure. The emergence and advances in sequencing technology provided a way to access genome information, namely to identify and study evolutionary macro-events, as well as chromosome alterations for clinical purposes. This paper describes a completely alignment-free computational method, based on a blind unsupervised approach, to detect large-scale and small-scale genomic rearrangements between pairs of DNA sequences. To illustrate the power and usefulness of the method we give complete chromosomal information maps for the pairs human-chimpanzee and human-orangutan. The tool by means of which these results were obtained has been made publicly available and is described in detail. Structural genomic rearrangements are a major source of intra-and inter-species variation. Chromosomal inversions, translocations, fissions and fusions, are part of the naturally occurring genetic diversity of individuals, are selectable and can confer environment-dependent advantages 1 . Chromosome rearrangements are also associated with disease, namely, developmental disorders and cancer. For example, many leukaemia patients present a reciprocal translocation between chromosomes 9 and 22, also known as the Philadelphia chromosome. This produces BCR-ABL fusion proteins that are constitutively active tyrosine kinases, contributing to tumour growth and proliferation 2 . Another striking example is the human inversion polymorphism in the 17q21 region, which contains the neurodegenerative disorder-associated gene MAPT (microtubule associated protein Tau). The direct oriented H1 haplotype is common and relates with increased Alzheimer's and Parkinson's disease risk, while the inverted H2 haplotype has higher frequencies in Southwest Asia and Southern Europe populations, particularly around the Mediterranean