[New aspects of the genetic heterogeneity of inborn errors of metabolism ].
New insight into the structure of eukaryotic genes on the one hand, and our knowledge of posttranslational protein modification and compartmentalization on the other, enable a more universal understanding of the genetic heterogeneity of inborn errors of metabolism. The fact that many genes are split into the coding exon-sequences and the non-coding intron-sequences necessitates the distinction of intron-alleles from exon-alleles. While intron-alleles affect the processing of the primary product of transcription, the exon-alleles correspond more or less to the classical alleles, i.e. to the structural alterations of the coding sequences. The repertory of possible alleles is further extended by the inclusion of regulatory sequences with a cis-dominant action. There are examples of the new concepts within the spectrum of multiple alleles causing various forms of thalassaemia. Our views on multiple allelism can no longer be based upon the paradigm of the classical gene. The concept of the functional unit provides a more promising approach.
D000483:Alleles; D001483:Base Sequence; D005799:Genes, Dominant; D006801:Humans; D008661:Metabolism, Inborn Errors / Q000235:genetics*; D009154:Mutation; D010441:Peptide Chain Elongation, Translational
Neue Aspekte der Heterogenität genetisch bedingter Stoffwechselkrankheiten.