The human XPG gene: gene architecture, alternative splicing and single nucleotide polymorphisms

Defects in the XPG DNA repair endonuclease gene can result in the cancer-pr one disorders xeroderma pigmentosum (XP) or the XP-Cockayne syndrome comple x. While the XPG cDNA sequence was known, determination of the genomic sequ ence was required to understand its different functions. In cells from norm al donors, we found that the genomic sequence of the human XPG gene spans 3 0 kb, contains 15 exons that range from 61 to 1074 bp and 14 introns that r ange from 250 to 5763 bp, Analysis of the splice donor and acceptor sites u sing an information theory-based approach revealed three splice sites with low information content, which are components of the minor (U12) spliceosom e, We identified six alternatively spliced XPG mRNA isoforms in cells from normal donors and from XPG patients: partial deletion of exon 8, partial re tention of intron 8, two with alternative exons tin introns 1 and 6) and tw o that retained complete introns (introns 3 and 9), The amount of alternati vely spliced XPG mRNA isoforms varied in different tissues. Most alternativ e splice donor and acceptor sites had a relatively high information content , but one has the U12 spliceosome sequence. A single nucleotide polymorphis m has allele frequencies of 0.74 for 3507G and 0.26 for 3507C in 91 donors. The human XPG gene contains multiple splice sites with low information con tent in association with multiple alternatively spliced isoforms of XPG mRN A.