Mutation analysis of the apoptotic "death-receptors" and the adaptors @entity45317 and XXXX / @entity23903 in @entity421 samples and @entity421 cell lines.

@entity462 @entity4106 @entity5 @entity1197 @entity3048 @entity25783 @entity3049 @entity45317 @entity421 @entity5187 @entity23903 @entity10736
Apoptosis is a key mechanism of the organism that regulates embryogenesis and development, maintains homeostasis of the immune system and removes potentially hazardous cells. A dysregulation of apoptosis signaling may thus disturb the balance of cell survival and cell death, leading to the development of several diseases including @entity5 . In order to determine whether @entity421 display an increased frequency of genetic alterations that affect apoptosis signaling, we analyzed the death domains of the death receptor genes @entity1197 /Fas/ @entity1197 , @entity10736 , @entity4106 / @entity4106 / @entity4106 /LARD/ @entity4106 , @entity3049 / @entity3049 / @entity3049 /KILLER, @entity25783 and the complete coding sequences of the death receptor gene @entity3048 / @entity3048 and the genes of the adaptors @entity45317 and @entity23903 / @entity23903 . The investigation included 15 @entity421 samples, 3 @entity421 cell lines (SAOS-2, @entity5187 and MG63) and peripheral blood from 20 donors as controls. We were able to identify 4 different sequence variations within the @entity3048 gene located on exons 3, 4, 5 and 10 (death-domain). No alterations have been detected in the other genes or exons investigated. Except the sequence variant affecting exon 4, the alterations were homozygous in 15% of the @entity5 samples and cell lines, whereas the same alterations found in the control group were heterozygous or even not detectable. Three out of 4 alterations are located in the receptor's extracellular @entity462 rich domain, which contains the ligand binding area and 1 on exon 10 coding for the death-domain. They may thus exert influence on ligand-receptor interactions and subsequent apoptosis induction. Our findings suggest that homozygous genetic alterations within the @entity3048 gene may be implicated in the formation of @entity421 .
