People With Down Syndrome Have 'Super Genome' - Study

02.02.2018

Children born with Down syndrome have an excellent genome in many ways—better, in fact, than the average genome of people without the genetic abnormality. It is possible that this genome offsets the disabilities caused by the extra chromosome, helping the baby to survive in the womb and grow and develop.

Trisomy 21 is a serious genetic disorder, but babies born with the condition grow up and can reach the age of 65. To explain this, researchers from the Universities of Geneva (UNIGE) and Lausanne (UNIL) hypothesised that people born with Down syndrome possess a high quality genome that has the ability to compensate for the effects of the third chromosome 21.

"Some genomes are of better quality than others, and can also be less prone to illnesses such as cancer," explains Stylianos Antonarakis, honorary professor in UNIGE's Faculty of Medicine, who led the research. Basing their work on the hypothesis of a the quality of the genome, the geneticists tested the gene variation, regulation and expression of 380 people with Down syndrome and compared them to people without the genetic disorder.

The first test consisted of observing the presence of rare variants, i.e. potentially harmful genetic mutations, in people with Down syndrome. A chromosome can have different rare variants in its two copies. In a person with Down syndrome, however, the rare mutations that are identical for all three copies of chromosome 21 are limited in number, reducing the total of potentially deleterious variants.

In a next step the geneticists studied the regulation of genes on chromosome 21. Each gene has switches that regulate its expression either positively or negatively. Since people with Down syndrome have three chromosomes 21, most of these genes are overexpressed. "But we discovered that people with Down syndrome have more regulators that diminish the expression of the 21 genes, making it possible to compensate for the surplus induced by the third copy," says Konstantin Popadin, a researcher at UNIL's Center for Integrative Genomics.

Finally, the researchers focused on the variation gene expression for the chromosomes of the entire genome. Each gene expression on a scale from 0 to 100 forms part of a global spread curve, with the median—50–considered the ideal expression. "For a normal genome, the expressions oscillate between 30 and 70, while for a person with Down syndrome, the curve is narrower around the peak that is very close to 50 for genes on all the chromosomes," continues professor Antonarakis. "In other words, this means that the genome of someone with Down leans towards the average—optimal functioning." Indeed, the smaller the gene expression variations are, the better the genome.

The UNIGE and UNIL geneticists were thus able to test the three functions of genomes of people with Down syndrome. "The research has shown that for a child with Down to survive pregnancy and then grow, his or her genome must be of a higher quality so that it can compensate for the disabilities caused by the extra copy of chromosome 21," concludes Popadin. These conclusions may also apply to other serious genetic disorders where pregnancies reach full term.

Science Daily. January 19. Genome Research. December 13.