Somatic mosaicism for copy number variation in differentiated human tissues
| Autor: | Carl E.G. Bruder, Andrzej Poplawski, E. Christopher Partridge, Rafal Bartoszewski, Maciej Krzyżanowski, Chiquito J. Crasto, Zsuzsa Bebok, Zbigniew Jankowski, Uwe Menzel, Robin Andersson, Jan Komorowski, Johanna Sandgren, Teresita Díaz de Ståhl, Adam Bogdan, Jan P. Dumanski, Desiree von Tell, Arkadiusz Piotrowski |
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| Rok vydání: | 2008 |
| Předmět: |
Genetics
Adult Polymorphism Genetic Somatic cell Genetic heterogeneity Mosaicism Gene Dosage Single-nucleotide polymorphism Genomics Biology Germline Structural variation Organ Specificity mental disorders Genetic variation Chromosomes Human Humans Genetic Predisposition to Disease Tissue Distribution Copy-number variation Genetics (clinical) Segmental duplication Oligonucleotide Array Sequence Analysis |
| Zdroj: | Human mutation. 29(9) |
| ISSN: | 1098-1004 |
| Popis: | Two major types of genetic variation are known: single nucleotide polymorphisms (SNPs), and a more recently discovered structural variation, involving changes in copy number (CNVs) of kilobase- to megabase-sized chromosomal segments. It is unknown whether CNVs arise in somatic cells, but it is, however, generally assumed that normal cells are genetically identical. We tested 34 tissue samples from three subjects and, having analyzed for each tissue < or =10(-6) of all cells expected in an adult human, we observed at least six CNVs, affecting a single organ or one or more tissues of the same subject. The CNVs ranged from 82 to 176 kb, often encompassing known genes, potentially affecting gene function. Our results indicate that humans are commonly affected by somatic mosaicism for stochastic CNVs, which occur in a substantial fraction of cells. The majority of described CNVs were previously shown to be polymorphic between unrelated subjects, suggesting that some CNVs previously reported as germline might represent somatic events, since in most studies of this kind, only one tissue is typically examined and analysis of parents for the studied subjects is not routinely performed. A considerable number of human phenotypes are a consequence of a somatic process. Thus, our conclusions will be important for the delineation of genetic factors behind these phenotypes. Consequently, biobanks should consider sampling multiple tissues to better address mosaicism in the studies of somatic disorders. |
| Databáze: | OpenAIRE |
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