Methods to analyse the human genome

There is much interest in the use of gene-specific probes for the study of dysfunction in human pathology. For the haemoglobinopathies, globin gene recombinants (either prepared from DNA sequences complementary to messenger RNA, or from genomic DNA) are used to determine whether globin genes are present, whether they are expressed in the nucleus, and whether they are correctly processed to give functional mRNAs. This has not only allowed a fuller understanding of the molecular aetiology of the thalassaemias, but also permitted antenatal diagnosis both by direct analysis of the gene lesion, and by linkage analysis using adjacent genes. Similar approaches are being applied to many other single gene defects. There are, however, other possible ways to study human hereditary disease using recombinants. It is now feasible to use random human chromosome-specific sequences to establish a linkage map for the entire human genome. Such a map may then be used either to determine the chromosomal localisation of any "single gene" phenotype by linkage analysis, or to study the contribution of different genes to a complex phenotype determined by several genes, as in multifactorial disease.