Navigation Links
Study tracks worldwide spread of beneficial blood cell gene variant
Date:7/28/2014

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 bone marrow transplant, 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."


'/>"/>

Contact: Jenny Gimpel
jenny.gimpel@kcl.ac.uk
44-020-784-84334
King's College London
Source:Eurekalert

Related medicine news :

1. Study Suggests Vaccine May Help Kids With Brain Cancer
2. Study reveals how cancer drug causes diabetic-like state
3. Coffee Drinking in Pregnancy Wont Lead to Sleepless Baby: Study
4. Lower GI problems plague many with rheumatoid arthritis, Mayo Clinic study finds
5. Veggies Like Broccoli, Cabbage May Help Fight Breast Cancer: Study
6. No Added Cancer Risk From Hip Replacement Materials: Study
7. Reported Decline in U.S. Pneumonia Deaths May Be False: Study
8. Early Study Finds Some Promise for Lung Cancer Vaccine
9. Narcissists Often Ace Job Interviews, Study Finds
10. Sexual objectification of female artists in music videos exists regardless of race, MU study finds
11. Soy may alleviate hot flashes in menopause, large-scale study finds
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/5/2016)... ... February 05, 2016 , ... Give To Cure ... to search for and donate to Give To Cure’s campaign that is crowdfunding clinical ... lets users make and share payments through a smart device. In 2015 alone, Venmo ...
(Date:2/5/2016)... ... February 05, 2016 , ... At its annual meeting held ... as Chairman of the National Board of Directors. Mr. McDermott succeeds former APDA Chairman, ... stated Leslie A. Chambers , APDA President and CEO. “Pat has tirelessly served ...
(Date:2/5/2016)... Francisco, CA (PRWEB) , ... February 05, 2016 ... ... and founder of CitiDent, announces that it is now welcoming orthodontist, ... Dr. Cheng, CitiDent offers a complete range of oral health care, including general ...
(Date:2/5/2016)... ... ... Health and wellness is a topic that should concern all Americans; however, it ... illness. Migraines are a severe form of a headache and often are accompanied by ... pain on their worst enemy, the feeling can last for many hours and be ...
(Date:2/5/2016)... ... February 05, 2016 , ... Calls Blacklist has just been updated ... interface design and the developer has fixed known bugs within the app. Calls Blacklist ... their phone while not consuming any of their device’s battery power or memory. It ...
Breaking Medicine News(10 mins):
(Date:2/5/2016)... Calif. , Feb. 5, 2016 Amgen (NASDAQ: ... th Annual Global Healthcare Conference at 9:15 a.m. ET ... City . David W. Meline , executive vice ... the conference. Live audio of the presentation can be accessed ... under Investors. A replay of the webcast will also be ...
(Date:2/5/2016)... a medical devices company, is one of five recipients to ... Terry McAuliffe,s office. ivWatch will be receiving the STEM ... to be held at the Science Museum of ... that have made significant contributions to science. ... ivWatch ...
(Date:2/5/2016)... , Feb. 5, 2016  Aralez Pharmaceuticals Inc. ... of POZEN Inc. ("POZEN") and Tribute Pharmaceuticals Canada Inc. ("Tribute") ... and shareholders of Tribute. The combined company will operate ... company with operations in Canada , ... United States . Under the terms of the ...
Breaking Medicine Technology: