Ancient DNA reveals the reason for high multiple sclerosis rates in Europe.

Illustration of ancient migration across Europe

The new study has found the genes that significantly increase a person’s risk of developing multiple sclerosis (MS) were introduced into north-western Europe around 5,000 years ago by sheep and cattle herders migrating from the east. CREDIT SayoStudio

Researchers have created the world’s largest ancient human gene bank by analysing the bones and teeth of almost 5,000 humans who lived across Western Europe and Asia up to 34,000 years ago.

By sequencing ancient human DNA and comparing it to modern-day samples, the international team of experts mapped the historical spread of genes – and diseases – over time as populations migrated.

The ‘astounding’ results have been revealed in four trailblazing research papers published today (10 January 2024) in the same issue of Nature and provide a new biological understanding of debilitating disorders.

The extraordinary study involved a large international team led by Professor Eske Willerslev at the Universities of Cambridge and Copenhagen, Professor Thomas Werge at the University of Copenhagen, and Professor Rasmus Nielsen at University of California, Berkeley and involved contributions from 175 researchers from around the globe.

The scientists found:

  • The startling origins of neurodegenerative diseases including multiple sclerosis
  • Why northern Europeans today are taller than people from southern Europe
  • How major migration around 5,000 years ago introduced risk genes into the population in north-western Europe – leaving a legacy of higher rates of MS today
  • Carrying the MS gene was an advantage at the time as it protected ancient farmers from catching infectious diseases from their sheep and cattle
  • Genes known to increase the risk of diseases such as Alzheimer’s and type 2 diabetes were traced back to hunter gatherers
  • Future analysis is hoped to reveal more about the genetic markers of autism, ADHD, schizophrenia, bipolar disorder, and depression

Northern Europe has the highest prevalence of multiple sclerosis in the world. A new study has found the genes that significantly increase a person’s risk of developing multiple sclerosis (MS) were introduced into north-western Europe around 5,000 years ago by sheep and cattle herders migrating from the east.

By analysing the DNA of ancient human bones and teeth, found at documented locations across Eurasia, researchers traced the geographical spread of MS from its origins on the Pontic Steppe (a region spanning parts of what are now Ukraine, South-West Russia and the West Kazakhstan Region).

They found that the genetic variants associated with a risk of developing MS ‘travelled’ with the Yamnaya people – livestock herders who migrated over the Pontic Steppe into North-Western Europe.

These genetic variants provided a survival advantage to the Yamnaya people, most likely by protecting them from catching infections from their sheep and cattle. But they also increased the risk of developing MS.

“It must have been a distinct advantage for the Yamnaya people to carry the MS risk genes, even after arriving in Europe, despite the fact that these genes undeniably increased their risk of developing MS,” said Professor Eske Willerslev, jointly at the Universities of Cambridge and Copenhagen and a Fellow of St John’s College, an expert in analysis of ancient DNA and Director of the project.

He added: “These results change our view of the causes of multiple sclerosis and have implications for the way it is treated.”

The age of specimens ranges from the Mesolithic and Neolithic through the Bronze Age, Iron Age and Viking period into the Middle Ages. The oldest genome in the data set is from an individual who lived approximately 34,000 years ago.

The findings provide an explanation for the ‘North-South Gradient’, in which there are around twice as many modern-day cases of MS in northern Europe than southern Europe, which has long been a mystery to researchers.

From a genetic perspective, the Yamnaya people are thought to be the ancestors of the present-day inhabitants of much of North-Western Europe. Their genetic influence on today’s population of southern Europe is much weaker.

Previous studies have identified 233 genetic variants that increase the risk of developing MS. These variants, also affected by environmental and lifestyle factors, increase disease risk by around 30 percent. The new research found that this modern-day genetic risk profile for MS is also present in bones and teeth that are thousands of years old.

“These results astounded us all. They provide a huge leap forward in our understanding of the evolution of MS and other autoimmune diseases. Showing how the lifestyles of our ancestors impacted modern disease risk just highlights how much we are the recipients of ancient immune systems in a modern world,” said Dr William Barrie, a postdoc in the University of Cambridge’s Department of Zoology and co-author of the paper.

Multiple sclerosis is a neurodegenerative disease in which the body’s immune system mistakenly attacks the ‘insulation’ surrounding the nerve fibres of the brain and spinal cord. This causes symptom flares known as relapses as well as longer-term degeneration, known as progression.

Professor Lars Fugger, a co-author of the MS study professor and consultant physician at John Radcliffe Hospital, University of Oxford, said: “This means we can now understand and seek to treat MS for what it actually is: the result of a genetic adaptation to certain environmental conditions that occurred back in our prehistory.”

Professor Astrid Iversen, another co-author based at the University of Oxford, said: “We now lead very different lives to those of our ancestors in terms of hygiene, diet, and medical treatment options and this combined with our evolutionary history means we may be more susceptible to certain diseases than our ancestors were, including autoimmune diseases such as MS.”

The Lundbeck Foundation GeoGenetics Centre – the resource underpinning the discoveries

The new findings were made possible by the analysis of data held in a unique gene bank of ancient DNA, created by the researchers over the past five years with funding from the Lundbeck Foundation.

This is the first gene bank of its kind in the world and already it has enabled fascinating new insights in areas from ancient human migrations, to genetically-determined risk profiles for the development of brain disorders.

By analysing the bones and teeth of almost 5,000 ancient humans, held in museum collections across Europe and Western Asia, the researchers generated DNA profiles ranging across the Mesolithic and Neolithic through the Bronze Age, Iron Age and Viking period into the Middle Ages. They compared the ancient DNA data to modern DNA from 400,000 people living in Britain, held in the UK Biobank.

“Creating a gene bank of ancient DNA from Eurasia’s past human inhabitants was a colossal project, involving collaboration with museums across the region,” said Willerslev.

He added: “We’ve demonstrated that our gene bank works as a precision tool that can give us new insights into human diseases, when combined with analyses of present-day human DNA data and inputs from several other research fields. That in itself is amazing, and there’s no doubt it has many applications beyond MS research.”

The team now plans to investigate other neurological conditions including Parkinson’s and Alzheimer’s diseases, and psychiatric disorders including ADHD and schizophrenia.

They have received requests from disease researchers across the world for access to the ancient DNA profiles, and eventually aim to make the gene bank open access.

The research was funded by a €8M grant from the Lundbeck Foundation, and conducted at the Lundbeck Foundation Geogenetics Centre at the University of Copenhagen.

Jan Egebjerg, Director of Research at the Lundbeck Foundation, said: “The rationale for awarding such a large research grant to this project, as the Lundbeck Foundation did back in 2018, was that if it all worked out, it would represent a trail-blazing means of gaining a deeper understanding of how the genetic architecture underlying brain disorders evolved over time. And brain disorders are our specific focus area.” 

‘Gene for chronic pain identified’ Do you have it?




 

'Gene for chronic pain identified'  Do you have it?

‘Gene for chronic pain identified’ Do you have it?

A “gene responsible for chronic pain has been identified”, reports the BBC. It said that this could lead to drugs for treating long-lasting back pain.




This story is based on research carried out in mice. Researchers found that deleting a gene called HCN2 from the pain-sensing nerves in mice stopped them from having the chronic hypersensitivity to pain caused by nerve damage. However, their ability to sense short-term (acute) pain, for example from heat or pressure, was not affected.

This research has highlighted a potential role for HCN2 in one type of chronic pain, called neuropathic pain, produced by damage to nerves themselves. However, it’s important to note that this study was in mice and looked at the effect of removing the HCN2 gene rather than using chemicals to block its function. Therefore, it cannot tell us whether this strategy will be successful in treating human forms of chronic pain. This knowledge may help scientists to develop drugs to target this kind of pain in the future, but much more research will be needed to determine whether this will be the case.

Where did the story come from?

The study was carried out by researchers from the University of Cambridge and the University of Cadiz. Funding was provided by the UK Biotechnology and Biological Sciences Research Council, the European Union, Organon Inc. and a Cambridge Gates Foundation studentship. The study was published in the peer-reviewed journal Science .

The BBC provides a good description of this study, clearly stating that it was carried out in mice.

What kind of research was this?

This was animal research looking at whether an ion channel protein called HCN2 might play a role in the sensing of pain. Ion channels are protein “pores” in the cell membrane that control the flow of electrically charged atoms into or out of the cell. In nerves this flow of ions is essential for allowing them to transmit signals.




The researchers say that the frequency with which the nerves involved in sensing pain send signals to the brain (called their rate of firing) affects how intense a pain is felt to be. This rate could be influenced by ion channels, including the HCN ion channel family.

The HCN1 and HCN2 members of the HCN ion channel family are present at high levels in nerves involved in sensations such as pain and touch. Previous experiments have suggested that HCN1 does not play a large role in sensing pain, so the researchers wanted to investigate whether HCN2 might be important in sensing pain.

Animal and laboratory research is often the best way to investigate the role of individual proteins in biological processes, as researchers can remove individual genes and see what effect this has. This type of research could not be carried out in humans.

What did the research involve?

The researchers looked at the role of the HCN2 ion channel in mice by genetically engineering them to lack the gene that produces this protein in their pain-sensing nerves. They then looked at what effect this had on the ability of the pain-sensing nerves to send signals, and on how the mice sensed pain.

The researchers initially tried genetically engineering mice to lack the HCN2 gene throughout their bodies, but this led to the mice having serious movement problems and dying before they reached six weeks of age. They then decided to remove the HCN2 gene in the pain-sensing nerves only, so that these widespread adverse effects would not occur.

The researchers tested the mice’s responses to pain using standard tests. For example, they tested how quickly they withdrew their feet in response to touching a hot or cold surface or to the application of pressure (called painful ‘stimuli’). They also tested these responses after injecting the mice with chemicals that cause inflammation and make normal mice hypersensitive to these painful stimuli.

Finally, they looked at the effect of exposing these mice to long-lasting pain caused by damage to their nerves. This type of pain is called neuropathic pain. They used a standard way of replicating this type of pain, by placing pressure on the mice’s sciatic nerve. This usually makes mice more sensitive to painful stimuli.

What were the basic results?

The researchers found that mice that were genetically engineered to lack the gene for HCN2 in their pain-sensing nerves had disruptions to the normal electrical processes that led to firing of these nerves.

The HCN2-lacking mice did not show any change to their pain threshold on short-term exposure to heat or pressure. However, when injected with chemicals that cause inflammation and make normal mice hypersensitive to heat- and pressure-induced pain, the HCN2-lacking mice did not show hypersensitivity to heat-induced pain.

The HCN2-lacking mice also displayed the usual hypersensitivity to pressure-induced pain after the injection also seen in normal mice.

If the genetically engineered mice received a nerve injury, they did not show the increase in sensitivity to heat, cold or pressure that normal mice with this injury showed.

How did the researchers interpret the results?

The researchers concluded that the presence of HCN2 is necessary for the sensing of pain caused by nerve injury, called neuropathic pain. They say that HCN2 also appears to have a role in sensing inflammation-associated pain. They say that chemicals that can selectively block HCN2 may be useful as pain medication to block the effects of neuropathic and inflammatory pain.

Conclusion

This research has highlighted a potential role for HCN2 in one type of chronic pain, called neuropathic pain. This knowledge may help scientists to develop drugs to target this kind of pain.

Neuropathic pain is pain that arises from damage to or disorders of the nervous system. For example, the pain associated with spinal cord injury, shingles or from tumours pressing on nerves is neuropathic. This type of pain is reportedly difficult to treat with drugs.

Scientists will now be interested in finding chemicals that can block the action of HCN2, and testing the effect that such chemicals have on pain-sensing in animals. As removing HCN2 completely in mice had serious adverse effects, scientists would have to ensure that they could block the protein in such a way that reduced pain but did not have these adverse effects. Any chemicals that show promise and appear to be safe would then need to be tested in humans.

It is important to point out that this process of drug development takes a long time and is not always successful, with some chemicals that seem to have an effect in animals not working in humans.

Patau’s syndrome – signs, causes and screening!




Patau's syndrome

Patau’s syndrome




Patau’s syndrome is a rare, serious genetic disorder caused by having an additional copy of chromosome 13 in some or all of the body’s cells. It’s also called trisomy 13.

Each cell normally contains 23 pairs of chromosomes, which carry the genes you inherit from your parents.

But a baby with Patau’s syndrome has three copies of chromosome 13, instead of two.

This severely disrupts normal development and, in many cases, results in miscarriagestillbirth, or the baby dying shortly after birth.

Babies with Patau’s syndrome grow slowly in the womb and have a low birth weight, along with a number of other serious medical problems.

Patau’s syndrome affects about 1 in every 5,000 births. The risk of having a baby with the syndrome increases with the mother’s age.

More than 9 out of 10 children (over 90%) born with Patau’s syndrome die during the first year.

About 5-10% of babies with less severe forms of the syndrome, such as partial or mosaic trisomy 13, live for more than a year.

 

Symptoms and features

Babies with Patau’s syndrome can have a wide range of health problems.

Their growth in the womb is often restricted, resulting in a low birth weight, and 80% will be born with severe heart defects.

The brain often doesn’t divide into two halves. This is known as holoprosencephaly.

When this happens it can affect facial features and cause defects, such as:

cleft lip and palate

an abnormally small eye or eyes (microphthalmia)

absence of one or both eyes (anophthalmia)

reduced distance between the eyes (hypotelorism)

problems with the development of the nasal passages

Other abnormalities of the face and head include:

smaller than normal head size (microcephaly)

skin missing from the scalp (cutis aplasia)

ear malformations and deafness

raised, red birthmarks (capillary haemangiomas)

Patau’s syndrome can also cause other problems, such as:




an abdominal wall defect where the abdomen doesn’t develop fully in the womb, resulting in the intestines being outside the body, covered only by a membrane – this is known as an exomphalos or omphalocoele

abnormal cysts in the kidneys

an abnormally small penis in boys

an enlarged clitoris in girls

There may also be abnormalities of the hands and feet, such as extra fingers or toes (polydactyly), and a rounded bottom to the feet, known as rocker-bottom feet.

Causes of Patau’s syndrome

Patau’s syndrome happens by chance and isn’t caused by anything the parents have done.

Most cases of the syndrome don’t run in families (they’re not inherited). They occur randomly during conception, when the sperm and egg combine and the foetus starts to develop.

An error occurs when the cells divide, resulting in an additional copy – or part of a copy – of chromosome 13, which severely affects the baby’s development in the womb.

In many cases, the baby dies before reaching full term (miscarriage) or is dead at birth (stillbirth).

In most cases of Patau’s syndrome (75-90%), a baby has a whole extra copy of chromosome number 13 in their body’s cells. This is sometimes known as trisomy 13 or simple trisomy 13.

In 5-10% of cases of Patau’s syndrome, genetic material is rearranged between chromosome 13 and another chromosome. This is called a chromosomal translocation.

Patau’s syndrome that arises because of this can be inherited. Genetic Alliance UK has more information about chromosome disorders.

In a further 5% of cases, only some cells have the extra copy of chromosome 13. This is known as trisomy 13 mosaicism. Occasionally, only part of one chromosome 13 is extra (partial trisomy 13).

The symptoms and features of both mosaicism and partial trisomy tend to be less severe than in simple trisomy 13, resulting in more babies living longer.

Screening for Patau’s syndrome

You’ll be offered a screening test for Patau’s syndrome – as well as Down’s syndrome (trisomy 21) and Edwards’ syndrome (trisomy 18) – from 10-14 weeks of pregnancy. The test assesses your chances of having a baby with these syndromes.

The screening test offered at 10-14 weeks of pregnancy is called the combined test because it involves a blood test and an ultrasound scan.

If the screening tests show that you have a higher risk of having a baby with Patau’s syndrome, you’ll be offered a diagnostic test to find out for certain whether your baby has the syndrome.

This test will check your baby’s chromosomes in a sample of cells taken from him or her.

Two techniques can be used to obtain the cell sample – amniocentesis or chorionic villus sampling (CVS). These are invasive tests to remove a sample of tissue or fluid so it can be tested for the presence of the extra copy of chromosome 13.

A newer test has recently been developed where a sample of blood from the mother is taken so that the baby’s DNA found within it can be tested. This is known as non-invasive prenatal testing, and is only available privately.

If you’re not able to have the combined screening test, you’ll be offered a scan that looks for physical abnormalities, including those found in Patau’s syndrome.

This is sometimes called the mid-pregnancy scan and is carried out when you’re between 18 and 21 weeks pregnant.

Read more about screening tests in pregnancy.

Treating and managing Patau’s syndrome

There’s no specific treatment for Patau’s syndrome. As a result of the severe health problems a newborn baby with the syndrome will have, doctors usually focus on minimising discomfort and ensuring the baby is able to feed.

For the small number of babies with Patau’s syndrome who survive beyond the first few days of life, their care will depend on their specific symptoms and needs.

If your baby is diagnosed with Patau’s syndrome, either before birth or shortly afterwards, you’ll be offered counselling and support.

Genetic testing for parents

Both parents will need to have their chromosomes analysed if their baby is affected by Patau’s syndrome caused by a chromosomal translocation.

Genetic testing is carried out to help parents plan for future pregnancies, rather than as part of the decision making process for the current pregnancy.

The test results will allow a more accurate assessment to be made of the likelihood of the syndrome affecting future pregnancies.

Other family members may also be affected and should be tested.

Read more about genetic testing and counselling.

Thalassaemia – get informed here




Thalassaemia

Thalassaemia

Thalassaemia is the name for a group of inherited conditions that affect a substance in the blood called haemoglobin.

People with the condition produce either no or too little haemoglobin, which is used by red blood cells to carry oxygen around the body. This can make them very anaemic (tired, short of breath and pale).

It mainly affects people of Mediterranean, South Asian, Southeast Asian and Middle Eastern origin.

There are a number of types of thalassaemia, which can be divided into alpha and beta thalassaemias. Beta thalassaemia major is the most severe type. Other types include beta thalassaemia intermedia, alpha thalassaemia major and haemoglobin H disease.

It’s also possible to be a “carrier” of thalassaemia, also known as having the thalassaemia trait. Thalassaemia carriers don’t have any serious health problems themselves, but are at risk of having children with the condition.


 

Symptoms of thalassaemia

Most people born with thalassaemia experience problems from a few months after birth. Less severe cases may not be noticeable until later in childhood or even until adulthood.

The main problems associated with thalassaemia are:

  • anaemia – severe tiredness (fatigue), weakness, shortness of breath, noticeably pounding, fluttering or irregular heartbeats (palpitations), and pale skin caused by the lack of haemoglobin
  • excess iron in the body – this is caused by the regular blood transfusions used to treat anaemia and it can cause problems with the heart, liver and hormone levels if untreated

Some people experience other problems such as delayed growth, weak and fragile bones (osteoporosis), and reduced fertility.

Read more about the symptoms of thalassaemia.

Causes of thalassaemia

Thalassaemia is caused by faulty genes that affect the production of haemoglobin.

A child can only be born with the condition if they inherit these faulty genes from both parents.

For example, if both parents have the faulty gene that causes beta thalassaemia major, there’s a 25% chance of each child they have being born with the condition.

The parents of a child with the condition are usually carriers of thalassaemia (see below). This means they only have one of the faulty genes that causes the condition.




Read more about the causes of thalassaemia.

Screening and testing for thalassaemia

Thalassaemia is often detected during pregnancy or soon after birth.

Screening for thalassaemia in pregnancy is offered to all pregnant women in England to check if there’s a risk of a child being born with the condition, and some types may be picked up during the newborn blood spot test (heel prick test).

Blood tests can also be carried out at any age to check for the condition or to see if you’re a carrier of a faulty gene that causes it.

Read more about screening and testing for thalassaemia.

Treatments for thalassaemia

People with thalassaemia major or other serious types will need specialist care throughout their lives.

The main treatments are:

  • Blood transfusions – regular blood transfusions are given to treat and prevent anaemia; in severe cases these are needed around once a month.
  • Chelation therapy – treatment with medications to remove the excess iron from the body that builds up as a result of having regular blood transfusions. Some people experience a build-up of iron even without transfusions and need treatment for this.

Eating a healthy diet, doing regular exercise and not smoking or drinking excessive amounts of alcohol can also help to ensure you stay as healthy as possible.

The only possible cure for thalassaemia is a stem cell or bone marrow transplant, but this isn’t done very often because of the significant risks involved.

Read more about how thalassaemia is treated and living with thalassaemia.

Outlook for thalassaemia

Although the main problems associated with thalassaemia can often be managed with treatment, it’s still a serious condition that can have a significant impact on a person’s life.

Even in mild cases with few symptoms, there’s still a risk you could pass on a more serious form of the condition to your children.

Without close monitoring and regular treatment, the most severe types can cause serious organ damage and can be life-threatening.

In the past, severe thalassaemia was often fatal by early adulthood. But with current treatments, average life expectancy is expected to increase significantly, with people likely to live into their 50s, 60s and beyond.

Carriers of thalassaemia (thalassaemia trait)

A carrier of thalassemia is someone who carries at least one of the faulty genes that causes thalassaemia, but doesn’t have the condition themselves. It’s also known as having the thalassaemia trait.

People with this trait won’t develop severe thalassaemia, but are at risk of having a child with the condition if their partner is also a carrier.

You can request a blood test to check if you’re a carrier of thalassaemia from your GP surgery or nearest sickle cell and thalassaemia centre.

Read more about being a thalassaemia carrier.

Turner syndrome – what are the signs and symptoms of Turner syndrome?




Turner syndrome

Turner syndrome

Turner syndrome is a genetic disorder that affects about 1 in every 2,000 baby girls and only affects females.

A girl with Turner syndrome only has one normal X sex chromosome, rather than the usual two (XX).




This chromosome variation happens randomly when the baby is conceived in the womb. It is not linked to the mother’s age.

 

Characteristics of Turner syndrome

Females with Turner syndrome often have a wide range of symptoms and some distinctive characteristics. Almost all girls with Turner syndrome:

are shorter than average

have underdeveloped ovaries (female reproductive organs), resulting in a lack of monthly periods and infertility

As height and sexual development are the two main characteristics, Turner syndrome may not be diagnosed until a girl fails to show sexual development associated with puberty, usually between the ages of 8 and 14 years.

Other characteristics of Turner syndrome can vary significantly between individuals.

 

Treating Turner syndrome

There is no cure for Turner syndrome, but many of the associated symptoms can be treated.

Girls and women with Turner syndrome will need to have regular health checks of their heart, kidneys and reproductive system throughout their lives. However, it is usually possible to lead a relatively normal and healthy life.




Life expectancy is slightly reduced, but it can be improved with regular health checks to identify and treat potential problems at an early stage.