title: Polymorphisms of the DNA repair gene XRCC1 and the frequency of somatic mutations at the glycophorin A locus in newborns.
abstract: Two DNA polymorphisms in the XRCC1 gene, a microsatellite repeat region in the 3' un-translated region (3'UTR) of the gene and a G-->A substitution resulting in an Arg to Gln amino acid change in codon 399, were examined in 189 newborns who had previously been studied for glycophorin A (GPA) N0 and NN variant frequencies (Vfs) in cord blood erythrocytes. The GPA analysis had revealed that 14 of the 189 had extreme NN Vfs ranging from 40 x 10(-6) to 1787 x 10(-6). Mean Vfs for the remaining 175 were N0=(4.8+/-2.80)x10(-6) and NN=(2.62+/-2.01)x10(-6). Seven alleles of a polymorphic tandem [AC](n) region of the XRCC1 gene were identified. No association between [AC](n) genotype and either N0 or NN Vfs was found amongst the group of 175 nor was the distribution of genotypes unusual for the group of 14 with extreme NN Vfs. Analysis of the 399Gln polymorphism revealed that for the group of 175, 36.0% were Arg/Arg, 49.7% Arg/Gln and 14.3% Gln/Gln and genotype had no influence on N0 and NN Vfs. However, the distribution of genotypes was significantly different in the group of 14 with extreme NN Vfs, 14.3% being Arg/Arg, 42.8% Arg/Gln and 42.8% Gln/Gln. The 14 newborns with extreme NN Vfs may represent a sub-group with an unidentified genotoxic exposure and/or predisposition to gene-duplication mutations or alternatively the high values could have arisen by increased clonal expansion of haemopoietic precursor cells carrying NN mutations. Our results suggest that carriers of the Gln/Gln genotype are over represented in this group but the role that the genotype has in the derivation of high NN Vfs remains to be resolved.
authors: Genetics Unit, Westlakes Research Institute, Moor Row, Cumbria, UK. caroline.relton@westlakes.ac.uk
authors: Caroline L
authors: CL
authors: Relton
authors: C Paul
authors: CP
authors: Daniel
authors: Ann
authors: A
authors: Fisher
authors: Diana S
authors: DS
authors: Chase
authors: John
authors: J
authors: Burn
authors: E Janet
authors: EJ
authors: Tawn
mesh_terms: D001483:Base Sequence; D017931:DNA Primers; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005838:Genotype; D006021:Glycophorins / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D009154:Mutation; D011110:Polymorphism, Genetic; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; D006021:Glycophorins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human