Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED, PGD type I) is an autosomal recessive disease enriched in the Finnish population. Previously, we have assigned APECED to a 2.6-cM interval on chromosome 21q22.3 by linkage analysis in 14 Finnish families. This subtelomeric region of 21q22.3 seems to have sequence features resulting in its under-representation in large insert genomic libraries, and only a few large insert clones have been available for positional cloning to date. Here, we report the refined localization of the APECED gene and a visual physical map of 800 kb covering the critical chromosomal region for the gene. In the construction of the physical map, the recently developed fiber FISH techniques were essential for the orientation of the cosmid PI, PAC, and BAC clones in relation to each other. We also localized two cDNAs within this genomic region by fiber FISH combined with the highly sensitive tyramide-based detection method. These data will facilitate the final cloning of the APECED gene and any other novel gene in this complex genomic region.
 ...
PMID:High-resolution physical and transcriptional mapping of the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy locus on chromosome 21q22.3 by FISH. 926 5

Exon trapping was performed from a partial cosmid, PAC, and P1 clone contig from human chromosome 21 between MX1 and 21qter to identify genes that may be involved in the pathogenesis of Down syndrome or several of the genetic diseases that map to chromosome 21q22.3. One 19-bp exon showed identity to three ESTs. The complete sequence of the EST clones, RT-PCR, and cDNA library screening were used to determine the full-length cDNA sequence of 2.2 kb with an open reading frame of 256-amino-acids. The putative 256-amino-acid peptide has homology with a hypothetical Caehorhabditis elegans protein of unknown function. Northern blot analysis of this gene, termed C21orf2 (chromosome 21 open reading frame 2), revealed two ubiquitously expressed mRNAs of 2.2 and 1.2 kb produced by use of alternative polyadenylation sites. Hybridization of the EST clones to a cosmid contig in chromosome 21q22.3 mapped C21orf2 just distal to PFKL, a critical mapping region for several genetic diseases. Comparison to publicly available genomic sequence, and additional data, revealed that the gene is split into seven exons over 10.5 kb, further refining the mapping position to only 1.2 kb distal to PFKL with the direction of transcription toward the centromere. The 5'UTR is contiguous with D21S400, and intron 2 contains a 52-bp VNTR polymorphism. Given its mapping position, C21orf2 is a candidate for involvement in disorders including autoimmune polyglandular disease type I (also called autoimmune polyendocrinopathy candidiasis ectodermal dystrophy or APECED) and the autosomal nonsyndromic deafness loci, DFNB8 and DFNB10. Mutation analysis using sequencing of RT-PCR and genomic DNA-derived PCR products, SSCP, and Southern and Northern blot analyses in APECED patients excluded C21orf2 as the gene for APECED.
 ...
PMID:Characterization of a novel gene, C21orf2, on human chromosome 21q22.3 and its exclusion as the APECED gene by mutation analysis. 946 97