AbstractOver one hundred genes have been isolated from the human genome and shown to be causally related to specific human genetic diseases. Studies with gene‐specific probes have demonstrated that the mutations resulting in a particular phenotype are highly heterogeneous as a group, ranging from alterations in transcription or RNA processing in the nucleus, through to errors in mRNA translation in the cytoplasm. Even where the gene‐specific probe is not available, defects have been localized to chromosomal regions by family studies. Recently developed methods for moving along the chromosome from a linked marker to the mutation are resulting in rapid advances in the understanding of many monogenic disorders.