TY - JOUR
T1 - Analysis of microsatellite instability and hypermutation of immunoglobulin variable genes in Werner syndrome
AU - Rosner, Karli
AU - Winter, David B.
AU - Skovgaard, Gunhild Lange
AU - Oshima, Junko
AU - Gearhart, Patricia J.
AU - Bohr, Vilhelm A.
PY - 2001/6/21
Y1 - 2001/6/21
N2 - Werner syndrome (WS) is a human premature aging syndrome, which is associated with high frequencies of neoplasia and genetic instability. We have examined the occurrence of microsatellite instability, which may result from defective mismatch repair, in lymphoblastoid cell lines derived from nine WS patients. Instability was measured at the D2S123 locus by gel analysis of PCR products. Three WS cell lines had 4-13% altered alleles, compared with 0% in the other six lines. The increased frequency of microsatellite instability could not readily be associated with overt cancer or any other known clinical condition in the three patients. To examine whether the WS defect affected the humoral immune system, we measured the hypermutation of immunoglobulin variable genes in peripheral blood cells from the WS patient who donated the cell line with the highest frequency of microsatellite instability. The frequency and pattern of mutation was similar to that from normal individuals, suggesting that the Werner protein is not involved in generating hypermutation.
AB - Werner syndrome (WS) is a human premature aging syndrome, which is associated with high frequencies of neoplasia and genetic instability. We have examined the occurrence of microsatellite instability, which may result from defective mismatch repair, in lymphoblastoid cell lines derived from nine WS patients. Instability was measured at the D2S123 locus by gel analysis of PCR products. Three WS cell lines had 4-13% altered alleles, compared with 0% in the other six lines. The increased frequency of microsatellite instability could not readily be associated with overt cancer or any other known clinical condition in the three patients. To examine whether the WS defect affected the humoral immune system, we measured the hypermutation of immunoglobulin variable genes in peripheral blood cells from the WS patient who donated the cell line with the highest frequency of microsatellite instability. The frequency and pattern of mutation was similar to that from normal individuals, suggesting that the Werner protein is not involved in generating hypermutation.
KW - Hypermutation
KW - Immunoglobulin variable gene
KW - Microsatellite instability
KW - Werner syndrome
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U2 - 10.1016/S0047-6374(01)00256-1
DO - 10.1016/S0047-6374(01)00256-1
M3 - Article
C2 - 11389928
AN - SCOPUS:0034994732
VL - 122
SP - 1121
EP - 1133
JO - Mechanisms of Ageing and Development
JF - Mechanisms of Ageing and Development
SN - 0047-6374
IS - 11
ER -