Genome Mosaicism: One Human, Multiple Genomes

摘要

With recent advances in genome-wide assays, it is becoming increasingly apparent that a human individual is made up of a population of cells, each with its own "personal" genome. Thus, mosaicism is perhaps much more common within multicellular organisms than our limited genomic assays have detected thus far, and may represent the rule rather than the exception. To what extent does it play a role in normal development and disease? Chromosomal mosaicism has been recognized clinically for decades, but the application of high-resolution genome-wide analysis tools, such as array comparative genomic hybridization and genomic single-nucleo-tide polymorphism (SNP) chips has allowed detection of events missed by karyotyping (1-3). Mosaicism for small intragenic copy number variants (CNVs) was detected in 10% of 30 molecularly diagnosed subjects (4), and extensive genomic CNVs have been found in clonal isolates of embryonic stem cells (5). In addition, varying levels of mosaicism have been reported in somatic human tissues, including the skin, brain, and blood, and in induced pluripotent stem cells (6-10). Therefore, our understanding of the frequency and effects of mosaicism is increasing with the development of ever more sensitive methods for detecting genomic variation.