-HEMOGLOBINOPATHIES_37722

-HEMOGLOBINOPATHIES_37722 - H emoglobinopathies...

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Unformatted text preview: H emoglobinopathies Hemoglobinopathies occupy a special place in human genetics for many reasons: They are by far the most common serious Mendelian diseases on a worldwide scale Globins illuminate important aspects of evolution of the genome and of diseases in populations Developmental controls are probably better understood for globins than for any other human genes More mutations and more diseases are described for hemoglobins than for any other gene family Clinical symptoms follow very directly from malfunction of the protein, which at 15 g per 100 ml of blood is easy to study, so that the relationship between molecular and clinical events is clearer for the hemoglobinopathies than for most other diseases TWO GROUPS OF HEMOGLOBINOPATHIES Hemoglobinopathies are classified into two main groups: The thalassemias are generally caused by inadequate quantities of the polypeptide chains that form hemoglobin. The most frequent forms of thalassemia are therefore the a- and b-thalassemias Alleles are classified into those producing no product ( a , b ) and those producing reduced amounts of product ( a +, b +). Abnormal hemoglobins with amino acid changes cause a variety of problems, of which sickle cell disease is the best known. The E6V (glutamic acid to valine at codon 6) mutation replaces a polar by a neutral amino acid on the outer surface of the b-globin molecule.. -Other amino acid changes can cause anemia, cyanosis, polycythemia (excessive numbers of red cells), methemoglobinemia (conversion of the iron from the ferrous to the ferric state), etc. I. MOLECULAR PATHOLOGY OF HEMOGLOBINS Sickle cell anemia is only one example of many mutant hemoglobins. Hb is unique in being of known structure and having so many well characterized natural variants: >500. ca. 95% result from a single amino acid substitution and when present give rise to a hemoglobinopathy. The effect of an amino acid replacement in Hb is best understood in terms of its location within the structure of the molecule. Changes in surface residues : These are usually innocuous because most of these residues have no specific function. I. MOLECULAR PATHOLOGY OF HEMOGLOBINS Sickle cell anemia is only one example of many mutant hemoglobins. Hb is unique in being of known structure and having so many well characterized natural variants: >500. ca. 95% result from a single amino acid substitution and when present give rise to a hemoglobinopathy. The effect of an amino acid replacement in Hb is best understood in terms of its location within the structure of the molecule. Changes in surface residues : These are usually innocuous because most of these residues have no specific function....
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-HEMOGLOBINOPATHIES_37722 - H emoglobinopathies...

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