Down’s signs ‘seen in stem cells’

The researchers suggest they may be able to develop treatments for children

Scientists have revealed the earliest developmental changes that lead to Down’s syndrome.

The team from Barts and the Royal London say the changes to embryonic stem cells are caused by the presence of an extra copy of chromosome 21.

The study, in the American Journal of Human Genetics, says the extra chromosome sets off a chain of genetic changes in the developing embryo.

The Down’s Syndrome Association welcomed the “excellent” research.

Down syndrome belongs to a group of conditions called “aneuploidies”, which are defined by an abnormal loss or gain of genetic material, such as fragments of chromosomes or whole chromosomes.

Aneuploidies cause congenital anomalies that are a prime cause of infant death in Europe and the US, and are currently on the increase with advancing maternal age in European countries.

Around one in every 1,000 babies born in the UK will have Down’s syndrome.

There are 60,000 people in the UK with the condition.

Therapeutic potential

The international team of researchers, which also included scientists from the US, Australia, Spain and Switzerland, looked at embryonic stem cells from mice which had been genetically engineered to carry a copy of human chromosome 21.

“It’s not just important for the development of brain cells but for their maintenance throughout life Professor Dean Nizetic

They discovered that the presence of the extra chromosome 21, known as trisomy 21, disturbs a key regulating gene called REST, which then disturbs the cascade of other genes that control normal development at the embryonic stem cell stage.

The scientists also found that one gene (DYRK1A) which is present on chromosome 21, acts as the trigger for this disturbance.

Dean Nizetic, professor of cellular and molecular biology at Barts and the London, said the work could one day lead to molecule-based therapies which could alleviate the effects of Down’s syndrome.

“We hope that further research might lead to clues for the design of new therapeutic approaches tackling developmental delay, mental retardation, ageing and regeneration of brain cells, and Alzheimer’s disease.

He said he believed the genetic effects continue throughout life.

“I suspect that it’s not just important for the development of brain cells but for their maintenance throughout life; how cells age and how they can cope with stress.

“That’s an area that could be approached with regard to therapies.”

‘Extremely positive’

Professor Nizetic suggested future research should be directed into basic molecular mechanisms that could one day develop into treatments to children with Down’s syndrome in the first few years of life when the brains are “plastic” and rapidly developing.

And he said that the same areas of the human genome have been thought to play a part in Alzheimer’s disease – so research could also lead to treatments for that condition.

Carol Boys, chief executive for the Down’s Syndrome Association said: “Any research that helps us to understand more about some of the complex medical conditions that are commonly associated with Down’s syndrome can only be a positive step forward.

“The development of therapeutic treatments for these sometimes complicated health problems that can be associated with the condition will hopefully lead to an improvement in the overall health of people of with Down’s syndrome.”

She added: “We understand that research is slow, but the initial results look extremely positive and we look forward to the continuation of the excellent work of this dedicated research team with interest.”

Roman Empire ‘raised HIV threat’

The Romans spread their genes far and wide

The spread of the Roman Empire through Europe could help explain why those living in its former colonies are more vulnerable to HIV.

The claim, by French researchers, is that people once ruled by Rome are less likely to have a gene variant which protects against HIV.

This includes England, France, Greece and Spain, New Scientist reports.

Others argue the difference is linked to a far larger event, such as the spread of bubonic plague or smallpox.

We’re waiting for the big piece of evidence which will solve this Dr Susan Scott Liverpool University

The idea that something carried by the occupying Romans could have a widespread influence on the genes of modern Europeans comes from researchers at the University of Provence.

They say that the frequency of the variant corresponds closely with the shifting boundaries of the thousand-year empire.

In countries inside the borders of the empire for longer periods, such as Spain, Italy and Greece, the frequency of the CCR5-delta32 gene, which offers some protection against HIV, is between 0% and 6%.

Countries at the fringe of the empire, such as Germany, and modern England, the rate is between 8% and 11.8%, while in countries never conquered by Rome, the rate is greater than this.

Legionnaire’s disease

However, the researchers do not believe that the genetic difference is due to Roman soldiers or officials breeding within the local population – history suggests this was not particularly widespread, and that invading and occupying armies could have been drawn not just from Italy but from other parts of the empire.

Instead, they say that the Romans may have introduced a disease to which people with the CCR5-Delta32 variant were particularly susceptible. This tallies with some other theories of why some have the gene variant, and some do not.

Researchers at the University of Liverpool had suggested that the variant could have offered protection against pandemics such as the Black Death which swept Europe on a regular basis during and after the Roman era.

These, said the Liverpool researchers, were viral illnesses which were lethal to people without the gene variant, raising its frequency from one in 20,000 people to approximately 10% in Northern Europe.

Dr Susan Scott, one of the researchers, said that the idea of Roman occupation being the driving force behind this was another theory to be considered.

“We just don’t know. This is just another piece of the jigsaw, but we’re waiting for the big piece of evidence which will solve this.”