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.


On friends and family

An interesting paper in PNAS by Nicholas Christakis and James H. Fowler claims that our friends are more closely related to us than random strangers. On average, we are related to our friends at a level close to that of fourth cousins. Maybe people have to go that far from their family before they can stand being around them without being forced to.

Beyond just the average similarities across the whole genome, they find that friends tend to be most similar in affecting the sense of smell, and most dissimilar in genes controlling immunity. The immunity one makes sense in that it would be good to hang around with people who are not susceptible to the same kinds of infections as you are.

Another fascinating result from the study is that genes that are more similar between friends seem to be evolving faster than other genes. This could also explain why humans evolution seems to have speeded up over the last 30,000 years. The authors suggest that the social environment is a force in driving the evolution of humans.

The authors use the Framingham Heart Study dataset to draw their conclusions which comprises of a relatively homogeneous population of European ancestry. It would be interesting to see whether these results hold up in other populations. Among other interesting results that the authors have claimed is that obesity is contagious.

Maybe this explains why certain people just click as friends even though you have extremely dissimilar tastes and temperaments and some people just don’t despite all usual indicators favoring a pairing. With the FDA ordering companies like 23andme from marketing health related results from its genetic tests, they could now  use the troves of data they have collected to not just tell you your potential ancestry and present relatives, but also suggest new friends. Someday you may be able to type in ‘suggest a friend’ into the searchbar and hit I’m feeling lucky and get a match genetically guaranteed to be better than the average stranger. India, of course, is no laggard here. Genomepatri is already available and all they have to do is tie up with a marriage portal and along with all the other data that goes into find an ideal match, you could also be guaranteed to find someone who is not just a spouse but a friend. I, for one, welcome the new GATTACA world.