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Credit: Graham Beards
Researchers have found evidence suggesting that beneficial variants of a gene controlling hematopoiesis exist in nearly all human populations.
The team analyzed genomic data from world populations, looking at HMIP-2, a human quantitative trait locus that affects the production of fetal hemoglobin in adults.
The analysis revealed 2 alleles that promote fetal hemoglobin production and can therefore reduce the severity of thalassemia and sickle cell anemia (SCA).
“Patients who have milder versions of [these] blood disorders, thanks to their ability to keep producing fetal hemoglobin, carry genetic clues that are helping us to understand the function of the genes and biological pathways involved in these diseases,” said Stephan Menzel, MD, of King’s College London in the UK.
He and his colleagues conducted this research and reported the results in Annals of Human Genetics.
The researchers noted that HMIP (HBS1L-MYB intergenic polymorphism) on chromosome 6q23.3 was first detected in a large Asian Indian family, where it was shown to be responsible for the persistence of fetal hemoglobin production in adulthood.
And HMIP-2 occupies a 24-kb stretch of DNA that acts as a distal upstream enhancer for MYB, the gene for cMYB, which is essential to hematopoiesis.
While studying 4 groups of SCA patients of diverse African descent, Dr Menzel and his colleagues discovered 2 alleles at HMIP-2 that promote fetal hemoglobin—HMIP-2A and HMIP2-B.
Subsequent analyses revealed the alleles were present, either alone or together, in major human populations and nearly all of the ethnic groups studied.
Both HMIP-2A and HMIP2-B 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 alone is common in Far-East Asian peoples and in Amerindians.
The researchers also analyzed genomic data from Neanderthals, Denisovans, and Great Apes, but detected neither HMIP-2A nor HMIP-2B.
The team said these results suggest MYB enhancer variants that modulate the severity of SCA and thalassemia 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, so the environmental factors that favored such variants in these early humans are not clear.
For the next stage of this research, Dr Menzel and his colleagues plan to 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. 
Credit: Graham Beards
Researchers have found evidence suggesting that beneficial variants of a gene controlling hematopoiesis exist in nearly all human populations.
The team analyzed genomic data from world populations, looking at HMIP-2, a human quantitative trait locus that affects the production of fetal hemoglobin in adults.
The analysis revealed 2 alleles that promote fetal hemoglobin production and can therefore reduce the severity of thalassemia and sickle cell anemia (SCA).
“Patients who have milder versions of [these] blood disorders, thanks to their ability to keep producing fetal hemoglobin, carry genetic clues that are helping us to understand the function of the genes and biological pathways involved in these diseases,” said Stephan Menzel, MD, of King’s College London in the UK.
He and his colleagues conducted this research and reported the results in Annals of Human Genetics.
The researchers noted that HMIP (HBS1L-MYB intergenic polymorphism) on chromosome 6q23.3 was first detected in a large Asian Indian family, where it was shown to be responsible for the persistence of fetal hemoglobin production in adulthood.
And HMIP-2 occupies a 24-kb stretch of DNA that acts as a distal upstream enhancer for MYB, the gene for cMYB, which is essential to hematopoiesis.
While studying 4 groups of SCA patients of diverse African descent, Dr Menzel and his colleagues discovered 2 alleles at HMIP-2 that promote fetal hemoglobin—HMIP-2A and HMIP2-B.
Subsequent analyses revealed the alleles were present, either alone or together, in major human populations and nearly all of the ethnic groups studied.
Both HMIP-2A and HMIP2-B 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 alone is common in Far-East Asian peoples and in Amerindians.
The researchers also analyzed genomic data from Neanderthals, Denisovans, and Great Apes, but detected neither HMIP-2A nor HMIP-2B.
The team said these results suggest MYB enhancer variants that modulate the severity of SCA and thalassemia 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, so the environmental factors that favored such variants in these early humans are not clear.
For the next stage of this research, Dr Menzel and his colleagues plan to 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.
Credit: Graham Beards
Researchers have found evidence suggesting that beneficial variants of a gene controlling hematopoiesis exist in nearly all human populations.
The team analyzed genomic data from world populations, looking at HMIP-2, a human quantitative trait locus that affects the production of fetal hemoglobin in adults.
The analysis revealed 2 alleles that promote fetal hemoglobin production and can therefore reduce the severity of thalassemia and sickle cell anemia (SCA).
“Patients who have milder versions of [these] blood disorders, thanks to their ability to keep producing fetal hemoglobin, carry genetic clues that are helping us to understand the function of the genes and biological pathways involved in these diseases,” said Stephan Menzel, MD, of King’s College London in the UK.
He and his colleagues conducted this research and reported the results in Annals of Human Genetics.
The researchers noted that HMIP (HBS1L-MYB intergenic polymorphism) on chromosome 6q23.3 was first detected in a large Asian Indian family, where it was shown to be responsible for the persistence of fetal hemoglobin production in adulthood.
And HMIP-2 occupies a 24-kb stretch of DNA that acts as a distal upstream enhancer for MYB, the gene for cMYB, which is essential to hematopoiesis.
While studying 4 groups of SCA patients of diverse African descent, Dr Menzel and his colleagues discovered 2 alleles at HMIP-2 that promote fetal hemoglobin—HMIP-2A and HMIP2-B.
Subsequent analyses revealed the alleles were present, either alone or together, in major human populations and nearly all of the ethnic groups studied.
Both HMIP-2A and HMIP2-B 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 alone is common in Far-East Asian peoples and in Amerindians.
The researchers also analyzed genomic data from Neanderthals, Denisovans, and Great Apes, but detected neither HMIP-2A nor HMIP-2B.
The team said these results suggest MYB enhancer variants that modulate the severity of SCA and thalassemia 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, so the environmental factors that favored such variants in these early humans are not clear.
For the next stage of this research, Dr Menzel and his colleagues plan to 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.