title: Somatic mosaicism for copy-neutral loss of heterozygosity and DNA copy number variations in the human genome.
abstract: BACKGROUND
  Somatic mosaicism denotes the presence of genetically distinct populations of somatic cells in one individual who has developed from a single fertilised oocyte. Mosaicism may result from a mutation that occurs during postzygotic development and is propagated to only a subset of the adult cells. Our aim was to investigate both somatic mosaicism for copy-neutral loss of heterozygosity (cn-LOH) events and DNA copy number variations (CNVs) in fully differentiated tissues.
  
  
  RESULTS
  We studied panels of tissue samples (11-12 tissues per individual) from four autopsy subjects using high-resolution Illumina HumanOmniExpress-12 BeadChips to reveal the presence of possible intra-individual tissue-specific cn-LOH and CNV patterns. We detected five mosaic cn-LOH regions >5 Mb in some tissue samples in three out of four individuals. We also detected three CNVs that affected only a portion of the tissues studied in one out of four individuals. These three somatic CNVs range from 123 to 796 kb and are also found in the general population. An attempt was made to explain the succession of genomic events that led to the observed somatic genetic mosaicism under the assumption that the specific mosaic patterns of CNV and cn-LOH changes reflect their formation during the postzygotic embryonic development of germinal layers and organ systems.
  
  
  CONCLUSIONS
  Our results give further support to the idea that somatic mosaicism for CNVs, and also cn-LOHs, is a common phenomenon in phenotypically normal humans. Thus, the examination of only a single tissue might not provide enough information to diagnose potentially deleterious CNVs within an individual. During routine CNV and cn-LOH analysis, DNA derived from a buccal swab can be used in addition to blood DNA to get information about the CNV/cn-LOH content in tissues of both mesodermal and ectodermal origin. Currently, the real frequency and possible phenotypic consequences of both CNVs and cn-LOHs that display somatic mosaicism remain largely unknown. To answer these questions, future studies should involve larger cohorts of individuals and a range of tissues.
authors.affiliation: Institute of Molecular and Cell Biology, University of Tartu, Riia 23, 51010, Tartu, Estonia. olga.zhilina@ut.ee.|Department of Genetics, United Laboratories, Tartu University Hospital, L. Puusepa 2, 51014, Tartu, Estonia. olga.zhilina@ut.ee.
authors.forename: Olga
authors.initials: O
authors.lastname: Žilina
authors.affiliation: Institute of Molecular and Cell Biology, University of Tartu, Riia 23, 51010, Tartu, Estonia. marina.koltsina@gmail.com.
authors.forename: Marina
authors.initials: M
authors.lastname: Koltšina
authors.affiliation: Institute of Molecular and Cell Biology, University of Tartu, Riia 23, 51010, Tartu, Estonia. raivo.raid@ut.ee.
authors.forename: Raivo
authors.initials: R
authors.lastname: Raid
authors.affiliation: Institute of Molecular and Cell Biology, University of Tartu, Riia 23, 51010, Tartu, Estonia. akurg@ebc.ee.
authors.forename: Ants
authors.initials: A
authors.lastname: Kurg
authors.affiliation: Department of Genetics, United Laboratories, Tartu University Hospital, L. Puusepa 2, 51014, Tartu, Estonia. neeme.tonisson@ut.ee.|Estonian Genome Center, University of Tartu, Riia 23b, 51010, Tartu, Estonia. neeme.tonisson@ut.ee.
authors.forename: Neeme
authors.initials: N
authors.lastname: Tõnisson
authors.affiliation: Competence Centre on Health Technologies, Tiigi 61b, 50410, Tartu, Estonia. andres.salumets@ccrmb.ee.|Department of Obstetrics and Gynaecology, University of Tartu, L. Puusepa 8, 51014, Tartu, Estonia. andres.salumets@ccrmb.ee.|Institute of Bio- and Translational Medicine, University of Tartu, Ravila 19, 50411, Tartu, Estonia. andres.salumets@ccrmb.ee.
authors.forename: Andres
authors.initials: A
authors.lastname: Salumets
mesh_terms: D000328:Adult; D001344:Autopsy; D056915:DNA Copy Number Variations; D005260:Female; D015894:Genome, Human; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009030:Mosaicism; D009928:Organ Specificity / Q000235:genetics; D020641:Polymorphism, Single Nucleotide