Children born with rare, inherited conditions known as Congenital Disorders of Glycosylation, or CDG, have mutations in one of the many enzymes the body uses to decorate its proteins and cells with sugars. Properly diagnosing a child with CDG and pinpointing the exact sugar gene that’s mutated can be a huge relief for parents — they better understand what they’re dealing with and doctors can sometimes use that information to develop a therapeutic approach. Whole-exome sequencing, an abbreviated form of whole-genome sequencing, is increasingly used as a diagnostic for CDG. But researchers at Sanford-Burnham Medical Research Institute (Sanford-Burnham) recently discovered three children with CDG who are mosaics — only some cells in some tissues have the mutation.
As we do more and more sequencing of the genome, we are going to see more of this – some people have a mixture of cells with totally different genomes in them. If we only look at one cell type, sya blood cells, we may thing someone has one genome when in fact their liver’s genome might be very different.
Or their liver might be a mixture of genomes. Or all sorts of complicated stuff.
In fact, work published at the end of last year demonstrated that most of us are a mosaic of different genomes. Different sin cells have a different genomic content than other skin cells. Blood cells were different than brain.
Not just in the DNA that was expressed but in the actual DNA present.
And, as this paper, above showed, the mosaic cells can even disappear. The cells with the genomes that were causing the problem actually vanished.
The team then went back to the three original children and examined their transferrin again. Surprisingly, these readings, which had previously shown abnormalities, had become normal. Freeze and his team believe this is because mutated cells in the children’s livers died and were replaced by normal cells over time.
Diagnosing genetic disease will get a lot more complicated before they get easier.