Trisomy 21, commonly called Down syndrome, is a genetic condition in which a person has 47 chromosomes instead of the usual 46 - three of the #21 chromosomes, rather than the usual two.(1)
Down syndrome is one of the most common genetic birth defects, affecting approximately one in 800 to 1,000 babies, and includes a combination of mental retardation, characteristic facial features and, often, heart defects, visual and hearing impairment, and other health problems.
It is very often accompanied by pathologies found in the general population: Alzheimer's disease, leukemia, or cardiac deficiency.
In a study conducted by Professor Stylianos Antonarakis' group from the Faculty of Medicine of the University of Geneva (UNIGE), researchers have identified the genomic variations associated with trisomy 21, determining the risk of congenital heart disease in people with Down syndrome. The targeted and specific study of chromosome 21 revealed two genomic variations, which, in combination, are the hallmark of hereditary cardiac deficiency.
Heart disease is a common disorder of Down syndrome. While the presence of a third gene in the n°21 pair (which characterizes the disease) increases the risk of heart disease, it is not the sole cause: genetic variations—or polymorphisms—as well as certain environmental factors also contribute to it. Genetic variations create the diversity of human beings, their predispositions, and the differences in the expression of similar genes.
Variations increase the risk of hereditary cardiac deficiency…
As part of a study carried out on the risk of congenital heart disease in people with Down syndrome, the geneticists observed the dominating role of two types of polymorphisms: the nucleotide - SNP, single-nucleotide polymorphism - and the variability in the number of copies of a gene - CNV, copy number variation.
To verify these observations, the scientists created a tailor-made chromosome 21; their analyses revealed two areas of variability in the number of copies of a gene (or CNV), and one area identified by a nucleotide polymorphism (or SNP), which can be associated with the risk of heart deficiency. Therefore, this study highlights the role of two CNVs and one SNP in the cardiac pathogenesis of people with Down syndrome for the first time, revealing the genetic complexity of a common symptom of trisomy 21.
For the authors of this study, the genetic architecture of the risk of congenital heart disease in individuals with Down syndrome must henceforth be understood as a complex combination, revealing the 21st chromosome, nucleotide polymorphism, and variability in the number of copies of a gene all at once; three factors to which we must add to the rest of the genome a still unidentified genetic variation, which Professor Antonarakis' group is already tracking.
These results are being published in the journal Genome Research and add to other research conducted by the same team about chronic myeloid leukemia, a severe form of leukemia that often affects people with Down syndrome. The journal Blood is publishing that study.
(1) 21 is not the only kind, it is now known. Other examples of trisomy include trisomy 18 and trisomy 13. The name "Down syndrome" comes from the physician Dr. Langdon Down, who described his collection of findings in 1866. In 1959 the cause of Down syndrome (the presence of a third #21 chromosome) was identified. Read more at Lucille Packard Children's Hospital at Stanford.