title: RSSsite: a reference database and prediction tool for the identification of cryptic Recombination Signal Sequences in human and murine genomes.
abstract: Recombination signal sequences (RSSs) flanking V, D and J gene segments are recognized and cut by the VDJ recombinase during development of B and T lymphocytes. All RSSs are composed of seven conserved nucleotides, followed by a spacer (containing either 12 +/- 1 or 23 +/- 1 poorly conserved nucleotides) and a conserved nonamer. Errors in V(D)J recombination, including cleavage of cryptic RSS outside the immunoglobulin and T cell receptor loci, are associated with oncogenic translocations observed in some lymphoid malignancies. We present in this paper the RSSsite web server, which is available from the address http://www.itb.cnr.it/rss. RSSsite consists of a web-accessible database, RSSdb, for the identification of pre-computed potential RSSs, and of the related search tool, DnaGrab, which allows the scoring of potential RSSs in user-supplied sequences. This latter algorithm makes use of probability models, which can be recasted to Bayesian network, taking into account correlations between groups of positions of a sequence, developed starting from specific reference sets of RSSs. In validation laboratory experiments, we selected 33 predicted cryptic RSSs (cRSSs) from 11 chromosomal regions outside the immunoglobulin and TCR loci for functional testing.
authors.affiliation: Institute for Biomedical Technologies, National Research Council, via Fratelli Cervi 93, 20090 Segrate, Milano, Italy. ivan.merelli@itb.cnr.it
authors.forename: Ivan
authors.initials: I
authors.lastname: Merelli
authors.forename: Alessandro
authors.initials: A
authors.lastname: Guffanti
authors.forename: Marco
authors.initials: M
authors.lastname: Fabbri
authors.forename: Andrea
authors.initials: A
authors.lastname: Cocito
authors.forename: Laura
authors.initials: L
authors.lastname: Furia
authors.forename: Ursula
authors.initials: U
authors.lastname: Grazini
authors.forename: Raoul J
authors.initials: RJ
authors.lastname: Bonnal
authors.forename: Luciano
authors.initials: L
authors.lastname: Milanesi
authors.forename: Fraser
authors.initials: F
authors.lastname: McBlane
mesh_terms: D000465:Algorithms; D000818:Animals; D030561:Databases, Nucleic Acid; D015322:Gene Rearrangement, B-Lymphocyte; D015329:Gene Rearrangement, T-Lymphocyte; D016678:Genome; D015894:Genome, Human; D023281:Genomics / Q000379:methods; D006801:Humans; D020407:Internet; D051379:Mice; D011995:Recombination, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D012984:Software