Multiple genes contribute to problems in memory and decision-making associated with Down’s syndrome, research suggests.
Scientists say that for the first time they have identified specific regions of a chromosome which cause these issues in mice with the condition.
They add that the finding provides new insight into the condition in humans.
Most people have 46 chromosomes – which carry genetic information – in each cell, divided into 23 pairs.
But people with Down’s syndrome have an extra copy of chromosome 21, which carries more than 200 genes.
In the study published in Cell Reports, scientists at University College London (UCL) used mouse models to try to find out how having these extra genes causes learning disabilities.
Chromosome 21 and its genes are also found in mice.
However, in the animals the genes have dispersed onto three smaller regions on three different chromosomes.
Co-author Professor Matthew Walker, also of UCL, said: “These findings are a complete surprise – we did not expect the three different gene groups would act completely differently.
“Scientists have traditionally worked on the hypothesis that a single gene, or single genes, was the likely cause of intellectual disabilities associated with Down syndrome.
“We have shown – for the first time – that different and multiple genes are contributing to the various cognitive problems associated with Down syndrome.”
Supported by Cardiff University and the Francis Crick Institute, researchers looked at the effect of the genes in each of the three different mouse regions, on learning and memory.
Three groups of mice were genetically modified to carry an extra copy of one of the gene groups on the identified mouse chromosomes.
Each group’s memory and decision-making ability was measured during navigation tests, where mice needed to negotiate a simple left-right T-maze.
The electrical activity in their brains was also monitored.
Researchers found that one of the mouse strains had worse memory, and irregular brain signals in a part of the brain called hippocampus – which is important for memory.
They also discovered another strain had worse decision-making ability and had poor brain signalling between the hippocampus and the pre-frontal cortex – needed for planning and decision-making.
The third strain had no unusual brain activity.
Corresponding author Professor Elizabeth Fisher, of UCL’s Queen Square Institute of Neurology, said: “Our study provides critical insights into the mechanisms underlying neuro-disability in Down syndrome and indicates that intellectual disability in Down syndrome may result from different underlying genetic, functional and regional brain abnormalities.
“This implies that therapies for people with Down syndrome should perhaps target multiple processes, and we have made the initial steps in identifying what some of these processes are.”
Researchers will now investigate specifically which gene or genes, within the smaller gene groups, are responsible for impaired memory and decision-making.
