医学遗传学.ppt

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医学遗传学ppt整理

Methods for profiling genome-wide DNA-methylation patterns Epigenetic response to extrinsic signals occurs through the transcriptional factors network. Altered DNA-methylation patterns in tumorigenesis. The hypermethylation of CpG islands of tumoursuppressor genes is a common alteration in cancer cells, and leads to the transcriptional inactivation of these genes and the loss of their normal cellular functions. This contributes to many of the hallmarks of cancer cells. At the same time, the genome of the cancer cell undergoes global hypomethylation at repetitive sequences, and tissue-specific and imprinted genes can also show loss of DNA methylation. In some cases, this hypomethylation is known to contribute to cancer cell phenotypes, causing changes such as loss of imprinting, and might also contribute to the genomic instability that characterizes tumours. Techniques for studying epigenetic changes in cancer. Most approaches to detecting DNA methylation start with the purification of DNA from cell samples. Subsequently, the overall DNA 5-methylcytosine content can be determined using high-performance capillary electrophoresis (HPCE) or high-performance liquid chromatography (HPLC), or the DNA methylation of specific candidate genes can be detected with methylation-sensitive methods. The epigenetic progenitor model of cancer The clonal genetic model of cancer Epigenetic gene-silencing events and tumorigenesis The role of miRNA hypermethylation in the metastatic behavior of human primary tumors. Methylation-specific PCR analyses for miR-148a, miR-34b/c, miR-9-1, miR-9-2, and miR-9-3 in primary human tumors derived from different tissues. The presence of a band under the U or M lanes indicates unmethylated or methylated sequences, respectively. Gene-transfer vectors that are used to treat hereditary disorders * * Using gene expression to investigate the genetic basis of complex disorders The identi?cation of complex disease susceptibility loci through genome-wide asso

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