Novel insight into chromosome 21 and its effect on Down syndrome

Scientists have identified specific regions of chromosome 21 which cause problems in memory and decision-making in mice with Down’s syndrome.

They say it is the first time the areas have been determined - and suggest the findings may provide 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 syndrome (DS) have an extra copy of chromosome 21, which carries more than 200 genes.

In the study, published in Cell Reports, researchers at University College London, supported by Cardiff University and the Francis Crick Institute, used mouse models to try and find out how having these extra genes causes learning disability.

Chromosome 21 and its genes are also found in mice.

However, the genes have dispersed on to three smaller regions on three different mouse chromosomes – 16, 10 and 17, containing 148 genes, 62 genes and 19 genes respectively.

Dr Tara Canonica, a researcher at Cardiff University’s School of Psychology, said: “We were very excited to observe that the three gene groups had different importance for memory function.

“Further testing in our laboratory in Cardiff has extended the crucial role of the chromosome 10 and 16 gene group, but not the chromosome 17 gene group, to a wider range of cognitive tests.

“Our findings help disentangle the complex relationship between gene overdosage and memory dysfunction in Down Syndrome.”
Co-author Professor Matthew Walker, of UCL, said the findings were “a complete surprise”.

“We did not expect the three different gene groups would act completely differently,” he said.

“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.”

The 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, which is needed for planning and decision-making.

Researchers will now investigate specifically which gene or genes, within the smaller gene groups, are responsible for impaired memory and decision-making.