Study may boost understanding of cause of Down syndrome

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Symptoms of Down syndrome are produced by gene impairments across every chromosome, not just one, according to a study that may bring new understanding to the most common genetic cause of intellectual disability.

Down syndrome occurs when there is an extra copy of chromosome 21, a condition called trisomy 21. In a study of twins, where only one had Down syndrome, a genomic analysis found that gene expression in the affected sibling had been altered throughout the genome.

Researchers have presumed for decades that Down syndrome is mainly caused by the overabundance of effects of chromosome 21 genes. The findings, published Wednesday in the journal Nature, show that a third copy of chromosome 21 disturbs the expression of all DNA in the genome. The surprise result may change understanding of Down syndrome’s symptoms, as well as other disorders caused by abnormal numbers of chromosomes, said Stylianos Antonarakis, a study author.

“The results of this study complicate the understanding of molecular mechanisms of the symptoms of trisomy 21 and opens a new hypotheses for all chromosomal abnormalities,” said Antonarakis, chairman of the Department of Genetic Medicine and Development at the University of Geneva Medical School in Switzerland, in an email.

About 6,000 U.S. babies are born with Down syndrome each year. In addition to cognitive impairment, people with the condition may also suffer from ailments including heart defects, low muscle tone, vision and hearing problems, and early onset Alzheimer’s disease. There is no cure.

The study compared a single set of identical twins in which just one twin had an extra chromosome 21. This unusual situation enabled researchers to study the effects of chromosome 21 without the bias of genome variability.

While gene expression has been studied extensively in Down syndrome, natural variations among individuals concealed the genome-wide effect of chromosome 21, researchers said.

The study found that gene dysregulation, or impairment, seen in the twin with Down syndrome is organized in domains or territories along all the different chromosomes.

“Thus trisomy 21 could be now viewed as a general genomic disorder, and genes throughout the genome could be involved in the different signs and symptoms,” Antonarakis said.

Humans normally have 46 chromosomes in each cell, divided into pairs. Chromosome 21 is the smallest human chromosome, accounting for less than 2 percent of the genome. Chromosome 21 probably contains 200 to 300 genes that provide instructions for making proteins.

The findings open the door to new research, said David Gilbert, professor of molecular biology at Florida State University in Tallahassee, who wrote an accompanying editorial to the study. Other conditions it may affect include Edwards syndrome, in which a person has three copies of chromosome 18, and Patau syndrome, in which a person has three copies of chromosome 13.

“It brings up whole new possibility on how disease can come about compared to how we were thinking,” Gilbert said.