Organization of the human FACC gene
- Hospital for Sick Children, Toronot (Canada); and others
Fanconi anaemia (FA) is an autosomal recessive disease characterized by progressive pancytopenia, chromosome instability and cellular sensitivity to DNA cross-linking agents. At least four complementation groups have been identified and the gene defective in complementation group C (FACC) has been cloned and the exon-intron organization determined by vectorette PCR. The FACC gene codes for a set of cDNAs that share the same coding region but differ at the 3{prime}UTR for the truncation at different points. Using cDNA probes 74 genomic clones were isolated. The 5{prime}UTRs have been located in phage 70, exons 1 and 2 in phage 66, and exons 4 and 5 in phage 37. As none of the 74 genomic clones carry exon 3, we are screening the genomic library with a specific probe for exon 3. The size of the introns has been determined: they range from 1 to 9 kb. The different clones span a region of more than 120 kb and we estimate that the FACC gene is at least 150 kb in size. The genomic organization of the 5{prime} and 3{prime}UTR has been established. In the 5{prime} region, exon -1 precedes exon -1a and an intron of 298 bp separates them. The 3{prime}UTR is not interrupted by any intron insertion which confirms the previous hypothesis suggesting that the size differences of the 3{prime}UTR are the result of transcriptional read-through of the first two polyadenylation signals. To provide some insight into the regulation of the FACC gene, the 5{prime} region has been functionally characterized with the luciferase assay system. 5{prime} deletion analysis of the FACC promoter region indicated that there was a substantial increase in luciferase activity in a fragment of 784 bp upstream of exon -1 and an inhibitory sequence between positions -311 and -570. Only a weak activity of luciferase was detected when the 298 bp intron between exon -1 and exon -1a was tested for transcriptional activity.
- OSTI ID:
- 133870
- Report Number(s):
- CONF-941009--
- Journal Information:
- American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
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