title: A fast and accurate method to detect allelic genomic imbalances underlying mosaic rearrangements using SNP array data.
abstract: BACKGROUND
  Mosaicism for copy number and copy neutral chromosomal rearrangements has been recently identified as a relatively common source of genetic variation in the normal population. However its prevalence is poorly defined since it has been only studied systematically in one large-scale study and by using non optimal ad-hoc SNP array data analysis tools, uncovering rather large alterations (> 1 Mb) and affecting a high proportion of cells. Here we propose a novel methodology, Mosaic Alteration Detection-MAD, by providing a software tool that is effective for capturing previously described alterations as wells as new variants that are smaller in size and/or affecting a low percentage of cells.
  
  
  RESULTS
  The developed method identified all previously known mosaic abnormalities reported in SNP array data obtained from controls, bladder cancer and HapMap individuals. In addition MAD tool was able to detect new mosaic variants not reported before that were smaller in size and with lower percentage of cells affected. The performance of the tool was analysed by studying simulated data for different scenarios. Our method showed high sensitivity and specificity for all assessed scenarios.
  
  
  CONCLUSIONS
  The tool presented here has the ability to identify mosaic abnormalities with high sensitivity and specificity. Our results confirm the lack of sensitivity of former methods by identifying new mosaic variants not reported in previously utilised datasets. Our work suggests that the prevalence of mosaic alterations could be higher than initially thought. The use of appropriate SNP array data analysis methods would help in defining the human genome mosaic map.
authors.affiliation: Center for Research in Environmental Epidemiology, Doctor Aiguader 88, Barcelona 08003, Spain. jrgonzalez@creal.cat
authors.forename: Juan R
authors.initials: JR
authors.lastname: González
authors.forename: Benjamín
authors.initials: B
authors.lastname: Rodríguez-Santiago
authors.forename: Alejandro
authors.initials: A
authors.lastname: Cáceres
authors.forename: Roger
authors.initials: R
authors.lastname: Pique-Regi
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Rothman
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.forename: Lluís
authors.initials: L
authors.lastname: Armengol
authors.forename: Luis A
authors.initials: LA
authors.lastname: Pérez-Jurado
mesh_terms: D022981:Allelic Imbalance; D002869:Chromosome Aberrations; D015894:Genome, Human; D006801:Humans; D009030:Mosaicism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D020641:Polymorphism, Single Nucleotide; D012680:Sensitivity and Specificity; D001749:Urinary Bladder Neoplasms / Q000235:genetics