Scientists have discovered two genes that seem to protect people against severe malaria. Both are members of complex family of HLA genes on chromosome 6, which are involved in the body’s immune response to infection. The findings are exciting because hey offer clues to the body’s defense mechanism against the Plasmodium parasites that cause the disease. Also, they provide part of the answer to a riddle that has long puzzled geneticists: why have we evolved with so many different forms of HLA genes?
The HLA or human leucocyte antigen, genes are the most variable in the genome- that is, there are more alleles, of alternative forms, of them than any other group. Each one codes for an antigen on the surface of cells, and no two people’s antigens are the same.
The HLA antigens enable cells of the immune system to recognize foreign proteins invading the body. T cells will recognize such proteins only when they are bound to HLA antigens. Class I HLA genes govern the killer T cells and Class II genes govern the helper T cells, making them organize other cells of the immune system to produce specific antibodies.
In theory, scientists argue, different HLA genes must protect people against different infectious diseases so natural selection has resulted in the large variety of genes. However, strong evidence for this theory has been hard to find. But the picture has changed. This is the first piece of data that strongly supports the theory of why the genes are polymorphic.
The researchers analyzed the HLA signatures of 1800 children where a quarter of all child deaths are from malaria. They classified the children into four groups: those with severe malaria that had affected the brain; those with severe malaria causing anemia; those with mild malaria –that is, symptoms but no physiological damage; the healthy children who acted as controls. The control children were matched with the cases for age and district.
The team took blood samples from each individual and studies the sequence of DNA encoding their HLA genes, using gene probes and the polymerase chain reaction. In the Class II genes, they found that a particular unit of several linked alleles which is usually inherited together was much rarer in the group with severe malarial anaemia than in the healthy controls. This unit of alleles, know as a haplotype, was also rarer, but less markedly so in the group with cerebral malaria.
For the Class I genes, children with severe malaria- both cerebral and anaemic - were much less likely than controls to have a particular allele of the HLA-B series which is much commoner. The researchers calculate that the alleles offer between 40 and 50 per cent protection against severe malaria.
The HLA or human leucocyte antigen, genes are the most variable in the genome- that is, there are more alleles, of alternative forms, of them than any other group. Each one codes for an antigen on the surface of cells, and no two people’s antigens are the same.
The HLA antigens enable cells of the immune system to recognize foreign proteins invading the body. T cells will recognize such proteins only when they are bound to HLA antigens. Class I HLA genes govern the killer T cells and Class II genes govern the helper T cells, making them organize other cells of the immune system to produce specific antibodies.
In theory, scientists argue, different HLA genes must protect people against different infectious diseases so natural selection has resulted in the large variety of genes. However, strong evidence for this theory has been hard to find. But the picture has changed. This is the first piece of data that strongly supports the theory of why the genes are polymorphic.
The researchers analyzed the HLA signatures of 1800 children where a quarter of all child deaths are from malaria. They classified the children into four groups: those with severe malaria that had affected the brain; those with severe malaria causing anemia; those with mild malaria –that is, symptoms but no physiological damage; the healthy children who acted as controls. The control children were matched with the cases for age and district.
The team took blood samples from each individual and studies the sequence of DNA encoding their HLA genes, using gene probes and the polymerase chain reaction. In the Class II genes, they found that a particular unit of several linked alleles which is usually inherited together was much rarer in the group with severe malarial anaemia than in the healthy controls. This unit of alleles, know as a haplotype, was also rarer, but less markedly so in the group with cerebral malaria.
For the Class I genes, children with severe malaria- both cerebral and anaemic - were much less likely than controls to have a particular allele of the HLA-B series which is much commoner. The researchers calculate that the alleles offer between 40 and 50 per cent protection against severe malaria.
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