NARROWING THE POSITION OF THE WERNER SYNDROME LOCUS BY HOMOZYGOSITY ANALYSIS - EXTENSION OF HOMOZYGOSITY ANALYSIS

Werner syndrome (WS) is an autosomal recessive disorder characterized by the premature occurrence of many age-related features. Previously, the WS gene (WRN) was mapped between D8S131 and D8S87, in an 8.3-cM in terval. In this study, regions of homozygosity in 36 WS patients from inbred families were searched for by genotyping for 35 dinucleotide re peat polymorphic markers to narrow down the WRN critical region. The r egion most consistently homozygous in these patients was between the D 8S1219/D8S1220 cluster and D8S278, within a 4.4-cM interval. For 16 ma rkers mapped in this interval, 24 WS patients (22 Japanese patients an d 2 Caucasian patients) in whom consanguinity failed to be proved were also genotyped, under the assumption that some of these patients migh t still be from consanguineous marriages. The data were analyzed by Fi sher's exact test with a 2 x 2 contingency table for the 22 Japanese p atients, excluding the 2 Caucasian patients. The frequencies of homozy gosity in the 22 patients at 10 of 16 markers tested were significantl y higher than those detected in the general population. Analysis of ho mozygosity patterns indicated that the region most consistently homozy gous was between D8S1445 and D8S278. Thus the WRN locus is most likely between the two markers D8S1445 and D8S278, in a 1.6-cM interval. (C) 1996 Academic Press, Inc.