Trisomy 21, also known as Down syndrome, is one of the most well-known forms of genetic conditions. The incidence of trisomy 21 is one in 700 live births.
Normally, healthy people are born with two copies of each of their 23 sets of chromosomes. However, people who have trisomy 21 are born with an additional, abnormal copy of chromosome 21.
How do geneticists explain that many children with trisomy 21 can survive up to the age of 65 under this chromosomal abnormality? The answer, it seems, might lie in the unique genome that these children possess.
A genome is essentially a whole, comprehensive set of genes that characterizes an individual. Stylianos Antonarakis, the honorary professor at the University of Geneva’s Faculty of Medicine, who is a pioneer in this research, explained that there is great variety within each person’s genome. Some genomes, it turns out, are more beneficial to sustaining health and less prone to developing illnesses.
“It’s the genome that determines what becomes of a person, and makes him or her grow up and grow old, with or without disease,” Antonarakis said, according to ScienceDaily.
After many studies, researchers from the University of Geneva (UNIGE) and University of Lausanne (UNIL) have come to the conclusion that children born with trisomy 21 have an innately superior genome that might be able to compensate for the defects found on their chromosome 21.
Antonarakis’ research team tested the genetic nuances of more than 380 subjects with trisomy 21, including their gene variation, regulation and expression. Afterwards, they compared the resulting data to normal subjects without trisomy 21.
The first genetic test aimed to observe trisomy 21 subjects who carry various deleterious mutations. While normal subjects carry two chromosome 21s, trisomy 21 subjects carry three. Therefore, there is a smaller probability that a specific mutation would be present on all three copies of their chromosome 21. This reduces the harmful effects of a specific mutation.
Additionally, the geneticists discovered that many genes on chromosome 21 are overexpressed for trisomy 21 patients. This was not surprising, considering three copies would be expected to have more expressions than two copies. However, Konstantin Popadin, a researcher at UNIL’s Center for Integrative Genomics, was particularly surprised to find out that people with trisomy 21 also have more regulators in their bodies that tune down the overexpression levels.
In the last portion of their research, Antonarakis’ team noticed that there is something special in the genome of a trisomy 21 subject.
“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,” Antonarakis said.
The medium score, 50, is considered to represent the optimal expression level. And indeed, this score matches the data obtained from the trisomy 21 subjects. As a conclusion, scientists deduced that for some specific factor, the genomes of trisomy 21 patients are more healthy and special.
From the three tests conducted above, geneticists from UNIGE and UNIL thus reached the belief that trisomy 21 produces higher quality genomes. Fetuses with an extra chromosome 21 survive through pregnancy and subsequent adulthood because many of their genes make up for the defects on trisomy 21, and those who don’t make it to childbirth often die because they lack such a strong genome.
Kyle Cunningham, a genetics professor in the department of biology at Hopkins, explained another way in which individuals with trisomy 21 might be less prone to developing illnesses.
“While trisomy 21 individuals have highly increased rates of leukemia, heart disease and other life-threatening maladies when young, they have greatly reduced rates of other kinds of tumors and cancers,” Cunningham said in an interview with The News-Letter.
