Construction of an ∼700-kb Transcript Map Around the Familial Mediterranean Fever Locus on Human Chromosome 16p13.3
- Michael Centola1,10,
- Xiaoguang Chen2,10,
- Raman Sood1,
- Zuoming Deng1,
- Ivona Aksentijevich1,
- Trevor Blake3,
- Darrell O. Ricke4,
- Xiang Chen1,
- Geryl Wood1,
- Nurit Zaks1,
- Neil Richards5,
- David Krizman6,
- Elizabeth Mansfield1,
- Sinoula Apostolou7,
- Jingmei Liu4,
- Neta Shafran1,
- Anil Vedula1,
- Melanie Hamon2,
- Andrea Cercek2,
- Tanaz Kahan2,
- Deborah Gumucio5,
- David F. Callen7,
- Robert I. Richards7,8,
- Robert K. Moyzis4,9,
- Norman A. Doggett4,
- Francis S. Collins3,
- P. Paul Liu3,
- Nathan Fischel-Ghodsian2, and
- Daniel L. Kastner1,11
- 1Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health (NIH), Bethesda, Maryland 20892-1820 USA; 2Departments of Pediatrics and Medical Genetics, Cedars-Sinai Medical Center, Los Angeles, California 90048-0750 USA; 3Genetics and Molecular Biology Branch, National Human Genome Research Institute, Bethesda, Maryland 20892 USA; 4Center for Human Genome Studies, Los Alamos National Laboratory, Los Alamos, New Mexico 87545 USA; 5Department of Anatomy and Cell Biology, University of Michigan, Ann Arbor, Michigan 48109-0616 USA; 6Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, Maryland 20892 USA; 7Department of Cytogenetics and Molecular Genetics, Adelaide Women’s and Children’s Hospital, North Adelaide, South Australia 5006; 8Department of Genetics, The University of Adelaide, Adelaide, South Australia 5000
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 (betweenD16S468/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.
Footnotes
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↵9 Present address: Department of Biological Chemistry, University of California at Irvine, Irvine, California 95616 USA.
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↵10 These authors contributed equally to this work and are listed in alphabetical order.
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↵11 Corresponding author.
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E-MAIL kastnerd{at}arb.niams.nih.gov; FAX (301)402-0012.
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- Received April 29, 1998.
- Accepted October 19, 1998.
- Cold Spring Harbor Laboratory Press
