Mitotic recombination is an important mutational event following oxidative damage.

The mutagenic effects of hydrogen peroxide (H(2)O(2)), a source of reactive oxygen species (ROS) have been determined in human lymphocytes. T-lymphocytes mutated at the autosomal HLA-A locus on chromosome 6 have been clonally isolated (N = 2097 clones) and the molecular basis of each clonal mutation characterised as due to intragenic, deletion or mitotic recombination mutation. H(2)O(2) caused a dose dependent increase in mutation frequency. There was no significant increase in the frequency of intragenic mutations. Mitotic recombination (MR) was responsible for 87% of the increase in mutation frequency induced by H(2)O(2) and gene deletion was responsible for 13%. MR results in loss of heterozygosity (LOH) distal to the recombination site. It is known that LOH is important in the initiation and progression of cancer. These results suggest that the biologically important consequence of some ROS may be LOH as a by-product of recombination repair. They also suggest that if our observations apply to ROS generally, then many of the mutations which accumulate with ageing or which are observed in cancer may be due to factors other than ROS.

Writer's cramp in an Australian pedigree with DYT1 dystonia.

Oppenheim's or DYT1 dystonia is a primary dystonia typically presenting in a limb at an early age and usually becoming generalised within 5 years. Over the last decade research into this debilitating disorder has progressed considerably, enabling the identification of a genetic lesion (a 3bp deletion in the DYT1 gene) now widely accepted as the cause of a majority of cases. This case report presents the first molecularly diagnosed pedigree of an Australian family with DYT1 dystonia, which presented as writer's cramp in the 15-year-old proband and two of his cousins.

Evidence for whole chromosome 6 loss and duplication of the remaining chromosome in acute lymphoblastic leukemia.

HLA class I molecules serve the essential immunological function of presenting antigen to CD8+ T lymphocytes. Tumor cells may present tumor-specific antigen to T cells via these molecules, but many tumors show a loss or down-regulation of HLA class I expression and this may serve as an immune escape mechanism. Using a microsatellite marker-based method, we have searched for loss of heterozygosity (LOH) mutations at 3 genomic regions implicated in HLA class I expression in a cohort of 56 acute lymphoblastic leukemia (ALL) samples. The regions analyzed consisted of the HLA class I heavy chain genes located within the MHC genomic region on chromosome arm 6p, the HLA class I light chain (beta-2-microglobulin, B2M) gene on chromosome arm 15q, and the putative HLA modifier of methylation gene (MEMO1) located on chromosome arm 1q. Results revealed low frequencies of B2M (2/55) and MEMO1 (5/42) LOH but a high frequency of MHC LOH (19/56) that was usually associated with whole chromosome 6 loss (13/19). Cytogenetic data were available for 30 samples, including nine of those that exhibited apparent whole chromosome 6 loss. No cases of chromosome 6 monosomy were observed. We propose that whole chromosome 6 loss with reduplication of the remaining chromosome is common in ALL and that it is driven by the presence of tumor-inhibiting factors on chromosome arm 6p (the HLA loci) along with previously localized tumor-suppressor genes on chromosome arm 6q.