Construction of an similar to 700-kb transcript map around the familial Mediterranean fever locus on human chromosome 16p13.3

We used a combination of cDNA selection, exon amplification, and computatio nal prediction from genomic sequence to isolate transcribed sequences from genomic DNA surrounding the familial Mediterranean fever (FMF) locus. Eight y-seven kb of genomic DNA around D16S3370, a marker showing a high degree o f linkage disequilibrium with FMF, was sequenced to completion, and the seq uence annotated. A transcript map reflecting the minimal number of genes en coded within the similar to 700 kb of genomic DNA surrounding the FMF locus was assembled. This map consists of 27 genes with discreet messages detect able on Northerns, in addition to three olfactory-receptor genes, a cluster of 18 tRNA genes, and two putative transcriptional units that have typical intron-exon splice junctions yet do not detect messages on Northerns. Four of the transcripts are identical to genes described previously, seven have been independently identified by the French FMF Consortium, and the others are novel. Six related zinc-finger genes, a cluster of tRNAs, and three ol factory receptors account for the majority of transcribed sequences isolate d from a 315-kb FMF central region (between D16S468/D16S3070 and cosmid 377 A12). Interspersed among them are several genes that may be important in in flammation. This transcript map not only has permitted the identification o f the FMF gene (MEFV), but also has provided us an opportunity to probe the structural and functional features of this region of chromosome 16.