title: Mosaic uniparental disomies and aneuploidies as large structural variants of the human genome.
abstract: Mosaicism is defined as the coexistence of cells with different genetic composition within an individual, caused by postzygotic somatic mutation. Although somatic mosaicism for chromosomal abnormalities is a well-established cause of developmental and somatic disorders and has also been detected in different tissues, its frequency and extent in the adult normal population are still unknown. We provide here a genome-wide survey of mosaic genomic variation obtained by analyzing Illumina 1M SNP array data from blood or buccal DNA samples of 1991 adult individuals from the Spanish Bladder Cancer/EPICURO genome-wide association study. We found mosaic abnormalities in autosomes in 1.7% of samples, including 23 segmental uniparental disomies, 8 complete trisomies, and 11 large (1.5-37 Mb) copy-number variants. Alterations were observed across the different autosomes with recurrent events in chromosomes 9 and 20. No case-control differences were found in the frequency of events or the percentage of cells affected, thus indicating that most rearrangements found are not central to the development of bladder cancer. However, five out of six events tested were detected in both blood and bladder tissue from the same individual, indicating an early developmental origin. The high cellular frequency of the anomalies detected and their presence in normal adult individuals suggest that this type of mosaicism is a widespread phenomenon in the human genome. Somatic mosaicism should be considered in the expanding repertoire of inter- and intraindividual genetic variation, some of which may cause somatic human diseases but also contribute to modifying inherited disorders and/or late-onset multifactorial traits.
authors.affiliation: Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, E-08003 Barcelona, Spain.
authors.forename: Benjamín
authors.initials: B
authors.lastname: Rodríguez-Santiago
authors.forename: Núria
authors.initials: N
authors.lastname: Malats
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Rothman
authors.forename: Lluís
authors.initials: L
authors.lastname: Armengol
authors.forename: Montse
authors.initials: M
authors.lastname: Garcia-Closas
authors.forename: Manolis
authors.initials: M
authors.lastname: Kogevinas
authors.forename: Olaya
authors.initials: O
authors.lastname: Villa
authors.forename: Amy
authors.initials: A
authors.lastname: Hutchinson
authors.forename: Julie
authors.initials: J
authors.lastname: Earl
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Marenne
authors.forename: Kevin
authors.initials: K
authors.lastname: Jacobs
authors.forename: Daniel
authors.initials: D
authors.lastname: Rico
authors.forename: Adonina
authors.initials: A
authors.lastname: Tardón
authors.forename: Alfredo
authors.initials: A
authors.lastname: Carrato
authors.forename: Gilles
authors.initials: G
authors.lastname: Thomas
authors.forename: Alfonso
authors.initials: A
authors.lastname: Valencia
authors.forename: Debra
authors.initials: D
authors.lastname: Silverman
authors.forename: Francisco X
authors.initials: FX
authors.lastname: Real
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.forename: Luis A
authors.initials: LA
authors.lastname: Pérez-Jurado
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000782:Aneuploidy; D016022:Case-Control Studies; D005260:Female; D018628:Gene Dosage; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D009030:Mosaicism; D020641:Polymorphism, Single Nucleotide; D024182:Uniparental Disomy; D001749:Urinary Bladder Neoplasms / Q000235:genetics; D055815:Young Adult