Major factors influencing linkage disequilibrium by analysis of different chromosome regions in distinct populations: demography, chromosome recombination frequency and selection.

Linkage disequilibrium (LD) mapping of disease genes is complicated by population- and chromosome-region-specific factors. We have analysed demographic factors by contrasting intermarker LD results obtained in a large cosmopolitan population (UK), a large genetic isolate (Sardinia) and a subisolate (village of Gavoi) for two regions of the X chromosome. A dramatic increase of LD was found in the subisolate. Demographic history of populations therefore influences LD. Chromosome-region-specific effects, namely the pattern and frequency of homologous recombination, were next delineated by the analysis of chromosome 6p21, including the HLA region. Patterns of global LD in this region were very similar in the UK and Sardinian populations despite their entirely distinct demographies, and correlate well with the pattern of recombinations. Nevertheless, haplotypes extend across recombination hot spots indicative of selection of certain haplotypes. Subisolate aside, chromosome-region-specific differences in LD patterns appear to be more important than the differences in intermarker LD between distinct populations.

An evaluation of the staging laparotomy in Hodgkin's disease.

A retrospective study was done on 33 patients who had staging laparotomies for Hodgkin's disease. The operation resulted in a significant change of stage in only four of the 33 patients (12%). We present opinions from authors supporting our belief that routine use of this procedure is not justified. Patients in stage I or II for whom limited radiotherapy is planned may benefit from the staging laparotomy. However, even some of these patients can be adequately treated with use of information from clinical staging only.