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Novel insight into chromosome 21 and its effect on Down syndrome

29 January 2020

A 香港六合彩-led research team has, for the first time, identified specific regions of chromosome 21, which cause memory and decision-making problems in mice with Down syndrome, a finding that provides valuable new insight into the condition in humans.听

people with Down syndrome have an extra copy of chromosome 21

Most people have 46 chromosomes in each cell, divided into 23 pairs: people with Down syndrome (DS) have an extra copy of chromosome 21, which carries over 200 genes.

In this study, published in听Cell Reports, researchers at 香港六合彩, 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, although the genes have dispersed onto three smaller regions on three different mouse chromosomes. These are mouse chromosomes 16, 10 and 17 containing 148 genes, 62 genes and 19 genes respectively.

The researchers looked at the effect of the genes in each of these three different mouse regions (chromosomes) on learning and memory. To do this three different mouse strains (groups of mice), were genetically modified to carry an extra copy of one of the gene groups on mouse chromosomes 16, 10 or 17.

During navigation tests, where mice needed to negotiate a simple 鈥榣eft-right鈥 T-maze, each group was measured for both memory and decision-making ability.

During these tests, the electrical activity of brain regions important for memory and decision-making was also monitored, using an听electroencephalogram (EEG).

The researchers found that one of the mouse strains (鈥楧p10Yey鈥 mice) had worse memory, and had irregular brain circuity (signals) in a part of the brain called hippocampus 鈥 which is known to be very important for memory.听

They also found another strain (鈥楧p1Tyb鈥 mice) had worse decision-making ability and had poor brain signalling between the hippocampus and the pre-frontal cortex 鈥 needed for planning and decision-making. And the third strain (鈥楧p17Yey鈥 mice) had no unusual electrical activity in the brain.

Co-author, Professor Matthew Walker (香港六合彩 Queen Square Institute of Neurology), said: 鈥淭hese findings are a complete surprise 鈥 we did not expect the three different gene groups would act completely differently.

鈥淪cientists have traditionally worked on the hypothesis that a single gene, or single genes, was the likely cause of intellectual disabilities associated with Down syndrome.

鈥淲e have shown 鈥 for the first time 鈥 that different and multiple genes are contributing to the various cognitive problems associated with Down syndrome.鈥

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

Corresponding author Professor Elizabeth Fisher (香港六合彩 Queen Square Institute of Neurology) said: 鈥淥ur study provides critical insights into the mechanisms underlying neuro-disability in Down syndrome and听indicates that intellectual disability in Down syndrome may result听from different underlying genetic, functional and regional brain abnormalities.

鈥淭his 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.鈥

Researchers were supported by grant funding from Wellcome. 听

Study note: Mouse strains Dp1Tyb, Dp10Yey and Dp17Yey were genetically modified to carry an extra copy of one of the gene groups on mouse chromosomes 16, 10 and 17 respectively.

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Image

  • Human male karotype with chromosome 21 highlighted: Credit

Media contact听

Henry Killworth

Tel: + 44 (0) 207 679 5296

E: h.killworth [at] ucl.ac.uk