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 interval. In this study, regions of homozygosity in 36 WS patients from inbred families were searched for by genotyping for 35 dinucleotide repeat polymorphic markers to narrow down the WRN critical region. The region most consistently homozygous in these patients was between the D8S1219/D8S1220 cluster and D8S278, within a 4.4-cM interval. For 16 markers mapped in this interval, 24 WS patients (22 Japanese patients and 2 Caucasian patients) in whom consanguinity failed to be proved were also genotyped, under the assumption that some of these patients might still be from consanguineous marriages. The data were analyzed by Fisher's exact test with a 2 x 2 contingency table for the 22 Japanese patients, excluding the 2 Caucasian patients. The frequencies of homozygosity in the 22 patients at 10 of 16 markers tested were significantly higher than those detected in the general population. Analysis of homozygosity patterns indicated that the region most consistently homozygous 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.
Nakura
J
J
Department of Geriatric Medicine, Osaka University Medical School, Osaka, 565, Japan.
Miki
T
T
Ye
L
L
Mitsuda
N
N
Zhao
Y
Y
Kihara
K
K
Yu
C E
CE
Oshima
J
J
Fukuchi
K I
KI
Wijsman
E M
EM
Schellenberg
G D
GD
Martin
G M
GM
Murano
S i
Si
Hashimoto
K
K
Fujiwara
Y
Y
Ogihara
T
T
D044466:Asian People / Q000235:genetics; D002874:Chromosome Mapping / Q000379:methods*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D003241:Consanguinity; D018900:Dinucleotide Repeats / Q000235:genetics; D005808:Genes, Recessive / Q000235:genetics; D005819:Genetic Markers; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007564:Japan; D014898:Werner Syndrome / Q000235:genetics*; D044465:White People / Q000235:genetics
D005819:Genetic Markers