The Globin Gene Mutations

Abstract

The known human globin gene mutations now total more than 400, representing a considerably larger number than for any other human protein system. By far the most numerous of these mutations are those resulting from replacements of single nucleotide bases, and most of these mutant genes are expressed by the synthesis of structurally abnormal globin chains having substitutions of one of their amino acid residues. The substantial number of hemoglobin variants that were well characterized as long as 20 years aga permitted the specific base changes of many of the globin gene mutations to be inferred even before the genetic code was fully known (Smith, 1962). After the complete triplet code was determined it could be shown that virtually all of the amino acid substitutions in these mutant globins could be explained by single base changes in affected codons. Although only few of the genes for the abnormal globins have thus far been sequenced, those that have been analyzed have fully corroborated the mutation codon assignments that were predicted from the genetic code. In many of the other forms of globin structural abnormalities, which include deletions and insertions of amino acid residues, the formation of abnormally shortened or elongated globin chains, and frameshift mutations, the underlying mutations could also be predicted reliably from known codon relationships in the genetic code. It was therefore possible to develop a comprehensive classification of the mutations underlying most of the structural globin variants well before the time that methods for the analysis of globin gene structure became available.

As the birth of living creatures, at first are ill-shapen, so are all innovations, which are the births of time.

F. Bacon: “Essays”