On mosaics and chimeras

Whenever we sequence a genome, we assume that there is one genome that an individual possesses. While we are aware that mutations may happen, in for example, cancer cells, the usual assumption is that all cells in the body contain more or less the same genome. In animals with multiple births, it is not uncommon to see chimeras produced by the merger of multiple fertilized eggs. This can be contrasted with mosaicism which denotes the presence of two or more populations of cells with different genotypes in one individual who has developed from a single fertilized egg. 

In most cases, mosaics or chimeras would not be detected unless some medical test shows it up. There have been famous cases like that of Foekje Dillema, a female athlete who was later on found to be an XX/XY chimera and stripped of her medals. In chimeric or mosaic individuals, different body cells may have different genomes. With increase in genetic testing by parents, especially when one of their children has a genetic disorder clinicians have figure out when the disorder-associated mutation arose: Did it spring up during the creation of the sperm or egg that contributed to the child’s genetic makeup, or did it come from the parents genetic makeup.

A recent paper in The American Journal of Human Genetics shows that mosaicism may be a lot more common than previously thought. From the paper’s abstract:

However, increasing sensitivity of genomic technologies has anecdotally revealed mosaicism for mutations in somatic tissues of apparently healthy parents. Such somatically mosaic parents might also have germline mosaicism that can potentially cause unexpected intergenerational recurrences. Here, we show that somatic mosaicism for transmitted mutations among parents of children with simplex genetic disease is more common than currently appreciated.

These results indicate that many of the widely used tests for identifying CNVs and either fail to detect many kinds of genetic alterations or lack the precision to distinguish mosaicism from completely constitutional alternations. These results suggest that higher genome resolution as obtained from high throughput sequencing might allow rearrangement-specific LR-PCR to become an inexpensive yet sensitive test for CNV mosaicism. In addition, there is a need for more sensitive and specific tests for identifying disorders arising from low-level mosaicism.