Linkage of tyrosinc bydroxylase to four other markers on the short arm of chromosome 11

Tyrosine hydroxylase is the rate-limiting enzyme in catecholamine synthesis; the gene has previously been cloned and localised to the short arm of chromosome II. Because of the interest in tyrosine hydroxylase as a candidate gene for manic-depressive psychosis and other affective disorders, we carried out family studies to determine the linkage of tyrosine hydroxylase with insulin, 0-globin, D11S12 and Harvey-ras 1, members of a linkage group which has previously been localised to lip. Using DNA from the Centre dYEtude du Polymorphisme Humain (CEPH) and from two large British pedigrees, we show that tyrosine hydroxylase is closely linked to these four loci (2=7.36, 6=0.04 for linkage to insulin) and suggest a gene order based on multipoint mapping