| Summary: | This project undertakes genetic and physical mapping studies on the A-chain gene of PDGF to refine the location of the gene on chromosome 7p. To further describe the structure of the gene and to develop polymorphic markers for linkage analysis, 8kb of gDNA from PDGFA was sequenced. This sequencing project identified polymorphic loci including a minisatellite and two dimorphic markers. This minisatellite, which is in intron 3 of the gene, lies less than 300 bp upstream from another minisatellite, in intron 4, which has been described previously (Bonthron 1992). The intron 3 minisatellite described in this project has a heterozygosity of about 56%, however some alleles are refractory to PCR amplification making it unsuitable for the large scale typing of data required for the linkage analysis. For this, the two dimorphisms were used. The linkage analysis placed <I>PDGFA</I> as the most distal locus in chromosome 7p, about 10 to 16 cM distal to the nearest proximal markers. Two maps using different sets of markers are presented. RARE (RecA-assisted restriction endonuclease) cleavage experiments showed that PDGFA lies about 630 to 679 kb from the telomere. Analysis for four different individuals indicated that there is a size variation. Polymorphic length variation in the subtelomeric regions has also been described for other chromosome telomeres. A telomeric location for PDGFA, which is a growth factor gene, is interesting since the loss of chromosome telomeres is associated with both ageing and malignancy. Loss of telomere repeats results in instability of the chromosome ends and may explain the increase in chromosome rearrangements seen in malignant cells. Such telomere rearrangements can have dramatic effects on the expression of nearby genes; for example truncation of the 16p telomere can silence expression from the nearby α-globin cluster. Expression of the gene has been shown to be silenced even when the gene itself is intact.
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