Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study tracks worldwide spread of beneficial blood cell gene variant

29.07.2014

Two beneficial variants of a gene controlling red blood cell development have spread from Africa into nearly all human populations across the globe, according to a new study led by King's College London.

The international team studied the genomes of world populations to look for the origin of changes in a key regulator gene which stimulate fetal haemoglobin production into adulthood. Fetal haemoglobin is normally found in fetuses and infants, but some patients with inherited blood disorders who are able to keep making it as adults experience milder symptoms of their condition.

Sickle cell anaemia is an inherited blood disorder in which red blood cells behave abnormally and can clog blood vessels, leading to acute unpredictable painful spells called a sickle cell crisis which typically last a week. The recurrent sickle crises and chronic anaemia lead to serious complications in the joints, bones, lungs, eyes, brain, liver and kidneys, and early death.

Thalassaemia is a group of inherited blood disorders where insufficient haemoglobin - the oxygen-carrier in blood cells - is produced, leading to anaemia. Symptoms of beta thalassaemia can range from moderate to severe, with the most severe form requiring blood transfusions for the rest of the person's life. The only 'cure' for both sickle cell anaemia and beta thalassaemia is a Sub-Saharan Africa, but this option is only available to a small number of patients.

Studies have shown that carriers of these conditions are protected against malaria; having one copy of the sickle cell gene significantly increases your chances of surviving malaria. As a result, these blood disorders are more prevalent in parts of the world where malaria is common. However, sickle cell disease is rapidly emerging as a public health issue both globally and in the UK where it is the most common severe genetic disorder, affecting an estimated 13,000 people.

The new study, published in the Annals of Human Genetics, looked at genetic factors that can reduce the severity of these blood disorders. Typically, our bodies make fetal haemoglobin whilst in the womb, but then switch to another form of haemoglobin, adult haemoglobin, at birth. However, we continue to produce very small amounts of fetal haemoglobin in adulthood, some more than others. Patients who have the genetic factors that increase fetal haemoglobin production tend to have milder symptoms of their blood disorder.

While studying patients of African and of South Asian descent, the authors noticed that one such factor, a genetic variant controlling the red blood cell regulator gene MYB - 'MYB enhancer variant' - on Chromosome 6, is of similar genetic structure not only in both patient groups, but also in healthy individuals, including those of Northern European origin, where thalassaemia and sickle cell disease are rare. This led the authors to suspect that beneficial MYB enhancer variants, which promote fetal haemoglobin in the body, are a general feature of human populations across the world and that they might have a common origin.

To test this hypothesis, the team searched for genetic signatures of such variants in public genome data generated from world populations to see whether they existed in other ethnic groups. They found signatures for two different types of MYB enhancer variants, HMIP-2A and HMIP-B, in major human population groups and in nearly all ethnic groups covered by the data. Both variants occur in Sub-Saharan Africa, but only at low frequencies. In much of the rest of the world the alleles have combined, forming HMIP-2A-B, and this combination is relatively common in Europe, South Asia and China. HMIP-2B separately is common in Far-East Asian peoples and in Amerindians, illustrating their connection across the Bering Strait.

The team also tested recent genome sequence data from our extinct cousins, the Neanderthals and Denisovans, and from the Great Apes, but detected neither HMIP-2A nor HMIP-2B. From this, the authors conclude that MYB enhancer variants that modulate the severity of sickle cell and beta thalassaemia have arisen twice in modern humans, in Africa, and then spread to the rest of the world. However, this likely occurred long before inherited blood disorders became prevalent, and thus the environmental factors that favoured such variants in these early humans are not clear.

The next stage of the research will explore which selection pressures or benefits might have contributed to the present population distribution of the variants. Selection pressures could include nutritional factors, such as the availability of iron in the diet, or specific demands on red blood cell production, such as adaptation to high altitudes.

Dr Stephen Menzel, co-author from the Department of Molecular Haematology at King's College London, says: "Patients who have milder versions of blood disorders, thanks to their ability to keep producing fetal haemoglobin, carry genetic clues that are helping us to understand the function of the genes and biological pathways involved in these diseases."

Professor Swee Lay Thein, co-author and Consultant Haematologist at King's College Hospital NHS Foundation Trust, says: "King's Health Partners cares for the largest cohort of sickle cell patients in the UK, with an estimated 2,500 patients. Although a newborn in the UK can now expect to live to adulthood, in adults the disorder has evolved into a chronic debilitating disease with acute or chronic pain and organ complications. We hope our research will help to develop biomarkers and ultimately, preventative treatments for inherited blood disorders."

###

The study, supported by funding from the Medical Research Council, was a collaboration of clinical and research expertise involving scientists and clinicians from international organizations and King's College London, King's College Hospital NHS Foundation Trust and Guy's and St Thomas' NHS Foundation Trust, part of King's Health Partners Academic Health Sciences Centre.

Jenny Gimpel | Eurek Alert!
Further information:
http://www.kcl.ac.uk

More articles from Life Sciences:

nachricht The birth of a new protein
20.10.2017 | University of Arizona

nachricht Building New Moss Factories
20.10.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Terahertz spectroscopy goes nano

20.10.2017 | Information Technology

Strange but true: Turning a material upside down can sometimes make it softer

20.10.2017 | Materials Sciences

NRL clarifies valley polarization for electronic and optoelectronic technologies

20.10.2017 | Interdisciplinary Research

VideoLinks
B2B-VideoLinks
More VideoLinks >>>