Linkage analysis of manic-depressive illness with dinucleotide repeats. The highly polymorphic dinucleotide repeats systems (microsatellites) are ideal for linkage analysis of complex diseases and also complement genetic maps obtained by using Southern blotting techniques. Multiplexing (simultaneous amplification of more than one microsatellite locus) with DNA samples from the bipolar pedigrees of the CNG branch collection has been implemented in our laboratory. Denaturing gradient gel electrophoresis (DGGE) of PCR amplified DNA is being utilized to scan for mutations in candidate disease genes, in multiple individuals, with great efficiency. Several collaborations with other NIH groups (NIDDK) involving the use of DGGE have has generated positive results. McCune-Albright syndrome: In some cases this disease is associated with a somatic activating mutation of Gs-alpha in exon 8 in affected tissues. This may be the basis of the molecular pathology of the disease. Insulin receptor gene (HIR): The insulin receptor genes of a patient with leprechaunism has been shown to bear a new mutation from each parent.