Construction of an ∼700-kb Transcript Map Around the Familial Mediterranean Fever Locus on Human Chromosome 16p13.3

Abstract

We used a combination of cDNA selection, exon amplification, and computational prediction from genomic sequence to isolate transcribed sequences from genomic DNA surrounding the familial Mediterranean fever (FMF) locus. Eighty-seven kb of genomic DNA around D16S3370, a marker showing a high degree of linkage disequilibrium with FMF, was sequenced to completion, and the sequence annotated. A transcript map reflecting the minimal number of genes encoded within the ∼700 kb of genomic DNA surrounding the FMF locus was assembled. This map consists of 27 genes with discreet messages detectable 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 olfactory receptors account for the majority of transcribed sequences isolated from a 315-kb FMF central region (between D16S468/D16S3070 and cosmid 377A12). Interspersed among them are several genes that may be important in inflammation. This transcript map not only has permitted the identification of the FMF gene (MEFV), but also has provided us an opportunity to probe the structural and functional features of this region of chromosome 16.Saturating the human genome with mapped genes so that the structure and function of each can be determined is an ultimate goal of the human genome project (Collins and Galas 1993). In addition

Caspases: evolutionary aspects of their functions in vertebrates

“…The existence of another CASP14 ‐like gene in humans has been suggested in a previous report (Centola et al , 1998). Although the mRNA for the CASP14 ‐like gene was detected in the database (accession number AF098666), it is difficult to understand whether gene products are functional because it is impossible to predict the open reading frame.…”

Ubiquitous SPRY domains and their role in the skeletal type ryanodine receptor

“…The functional importance of SPRY domains is indicated by diseases caused by point mutations in their sequences. Familial Mediterranean fever (FMF), a recessively inherited disorder, is characterised by recurrent episodes of fever and serosal inXammation (Bakkaloglu 2003;Centola et al 1998;Chae et al 2003;Papin et al 2007) without apparent high-titer antibodies or antigen speciWc T-cells (Chae et al 2000;Stojanov and Kastner 2005). More than 50 missense mutations in the MEFV (Mediterranean fever) gene have been identiWed (Chae et al 2006).…”

MEFV Gene-Related Enterocolitis Account for Some Cases Diagnosed as Inflammatory Bowel Disease Unclassified

“…Under physiological conditions, pyrin is a part of a protein complex named inflammasome and regulates activation of the inflammatory cytokine interleukin (IL)-1β [8]. Persistence of inflammation caused by dysfunction of pyrin is thought to be involved in the development of symptoms of FMF [9]. FMF is diagnosed on the basis of clinical symptoms, the Tel-Hashomer criteria having been accepted in ethnic groups with a high incidence of this condition [4].…”