RESUMEN
Variation in gene coding sequence represents a significant factor in predisposition to disease, including cancer. Variants of some DNA repair genes (e.g. MLH1, MSH2 and MSH6) are known to predispose to cancer. We identified single nucleotide polymorphisms (SNPs) in five DNA repair genes in 142 healthy individuals using a DNA sequencing protocol optimized for the direct detection of single nucleotide polymorphisms. This approach, called the heterozygote sequencing protocol (HSP), enables moderate-scale population surveys of SNPs. HSP uses fluorescently tagged primers and exploits the large dynamic range and low background of automated fluorescent sequencing. HSP may be used for any sequence that can be amplified by PCR. A total of 12 SNP variants in MGMT, ERCC1, CDK7, CCNH and XRCC4 were identified, 11 at polymorphic frequencies, with an average frequency of 0.22 (95% confidence interval 0.20-0.24). Among the 82 individuals for whom complete SNP profiles were available, no one person carried the GenBank reference sequence for all five genes. The extensive heterogeneity observed in these five genes is intriguing. All variants are in Hardy-Weinberg equilibrium, although the meaning of this equilibrium is unclear. Using this approach, possible associations of sequence variation, and hence of variation in DNA repair, with disease risk can be assessed.
Asunto(s)
Quinasas Ciclina-Dependientes , Reparación del ADN/genética , Endonucleasas , Polimorfismo de Nucleótido Simple , Adolescente , Adulto , Islas de CpG/genética , Proteínas de Unión al ADN/genética , Variación Genética , Heterocigoto , Humanos , Persona de Mediana Edad , O(6)-Metilguanina-ADN Metiltransferasa/genética , Proteínas Serina-Treonina Quinasas/genética , Proteínas/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Análisis de Secuencia de ADN , Quinasa Activadora de Quinasas Ciclina-DependientesRESUMEN
Footprint impressions of 107 male adults ranging in age from 19 to 67 years were recorded and examined. Included in this study were foot impressions from a pair of monozygotic twins as well. The impressions were recorded and converted into a set of indices which essentially are width-versus-length ratios of prominent features of the human foot. These indices were then correlated to yield probability values for use in this study and for comparison to data published by previous investigators Qamra, Abbott, Lovejoy, Cassidy, and Robbins. Friction ridge minutae were not considered in this study. Crease marks, well impressions, and toe step measurements were considered, but not incorporated in the probability values, because of the unique aspect of these features and the inability, at present, to convert these features to mathematical indices. These features do, however, introduce a subjective nature to the analysis scheme. This study uses the combined index probabilities of foot impressions so that the data generated can be used to assign a given probability that a particular foot impression, even without clear definable individual features, can be linked to the person who made the impression.
