Position effect in human genetic disease.

The spatially, temporally and quantitatively correct expression of a gene requires the presence not only of intact coding sequence, free of adverse nucleotide changes, but also correctly functioning regulatory control. With the identification of an increasing number of disease-related genes, the molecular defect in many cases has been defined. It is becoming clear that it is not always the transcription unit that bears the defect: there are a number of cases where the regulation of gene expression has been compromised. Cases associated with chromosomal rearrangement outside the transcription and promoter regions are categorized as position effects. A number of different mechanisms may explain their aetiology. Here, we examine the human disorders where such position effects are implicated. Further study of such cases may lead to important insights into mechanisms of gene regulation and transcriptional control.