Evidence against DNA polymerase β as a candidate gene for Werner syndrome.

Autor: Chang, Ming, Burmer, Glenna, Sweasy, Joann, Loeb, Lawrence, Edelhoff, Susanne, Disteche, Christine, Yu, Chang-En, Anderson, Leojean, Oshima, Junko, Nakura, Jun, Miki, Tetsuro, Kamino, Kouzin, Ogihara, Toshio, Schellenberg, Gerard, Martin, George
Zdroj: Human Genetics; 1994, Vol. 93 Issue 5, p507-512, 6p
Abstrakt: Werner syndrome (WS) is a rare autosomal recessive disorder of humans characterized by the premature onset and accelerated rate of development of several major age-related disorders. An aberration in DNA replication or repair is suggested by the evidence of genome instability. Since the structural gene for DNA polymerase β maps within the region of the WS mutation on the short arm of chromosome 8 and is involved in both DNA repair and DNA replication, we evaluated its candidacy as the WS gene. Several independent lines of evidence did not support that hypothesis: (1) activity gels showed normal enzyme activity and electrophoretic mobility; (2) nucleotide sequence analysis of the entire coding region failed to reveal mutations (although indicated mistakes in the published sequence); (3) single-strand conformation polymorphism (SSCP) and heteroduplex analyses failed to reveal evidence of mutations in the promoter region; (4) a newly discerned polymorphism failed to reveal evidence of homozygosity by descent in a consanguineous patient; and 5) fluorescence in situ hybridization (FISH) analysis placed the DNA polymerase β gene centromeric to D8S135 at 8p11.2 and thus beyond the region of peak LOD scores for WS. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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