Abstract
BackgroundSomatic 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.ResultsWe 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.ConclusionsOur 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1916-3) contains supplementary material, which is available to authorized users.
Highlights
Somatic mosaicism denotes the presence of genetically distinct populations of somatic cells in one individual who has developed from a single fertilised oocyte
Chromatid nondisjunction, erroneous DNA replication, faulty DNA repair mechanisms and recombination can lead to genetic alterations, such as aneuploidy, DNA copy number variations (CNVs), including deletions and duplications of chromosomal segments, or reciprocal loss and gain events that appear as copy-neutral loss of heterozygosity or acquired uniparental disomy (UPD) [5]
We identified 15 non-mosaic germ-line CNVs that were present in all tissues studied from a single individual
Summary
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 mutations of different scales that are propagated to only a subset of the adult cells during early development of the individual or later on during aging [1,2,3,4]. Mosaicism does not have any phenotypic consequences and in others exhibits a diverse range of clinical phenotypes depending on the fraction of mosaicism within a given tissue Due to this fact, and because of the lack of appropriate methods and large datasets, until recently it was impossible to estimate accurately the frequency of mosaicism within the general population [5, 7]. The structural genetic mosaicism was estimated based on either blood or buccal sample analysis, representing the mosaicism within a single tissue
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