Recombinant human DNA fragments hybridizing to a murine cDNA plasmid for the acute phase protein Serum Amyloid A (SAA) have been isolated; direct DNA sequencing of one has shown that it contains the coding region for the SAA protein in man. These fragments will be further characterized by DNA sequence analysis, restriction endonuclease digestion and nucleic acid hybridization to determine the precise chromosomal structure of the human SAA gene(s). Other features which will be studied include the organization of intron and exon regions in the genes, the nature of the 5' flanking sequences (the likely location of control information), the relation of the genes to one another (the possible existence of a gene family), the possibility of the presence of pseudogenes and the chromosomal location(s) for the SAA gene(s) of man. These basic studies will result in preparation of recombinant DNA gene probes suitable for analyzing the structure of human SAA genes and their expression. Using recombinant gene probes for human SAA, the expression and structure of the chromosomal loci will be studied in genetic disorders known to involve the SAA protein: familia Mediterranean fever and lattice corneal dystrophy as well as the genetic neuropathic amyloidoses where the SAA protein may be involved. Specific questions to be anwered are: do specifc SAA gene changes result in SAA proteins more likely to form the amyloid fibrils in these disorders? Do different SAA proteins underlie the different renal complications from amyloidosis in familiar Mediterranean fever in different population groups? Are specifc SAA genes expressed in any of these disorders? Are there SAA gene structure change which are diagnostically useful for detecting these genetic diseases? The basic study techniques are Southern blot hybridization and sequencing. Finally, SAA gene expression and control will be examined in chronic disorders associated with high serum levels and clinical amyloid deposition - primarily rheumatoid arthritis and metastatic malignancy as well as aging. Control methods of SAA expression which will be sought include: altered gene methylation and local structural gene changes including duplications, mutations, deletions and insertions.