Heritability and biological consequences of human variation in mitotic recombination

我们体内的细胞不断遭受遗传物质(基因)的损害，其中大部分都得到了有效的修复。有些则不是，细胞中基因的累积损伤可能会引发癌症。从最早的生命形式开始，细胞就进化出了几种修复机制。一种修复机制同源重组修复，作为其活性的一个次要副产品，会产生一种称为有丝分裂重组(MR)的事件。MR会导致基因多样性的丧失，这可能会导致癌症，而不是预防癌症。我们已经证明，MR在人类中的发生率差异非常大。在这个项目中，我们将设计一种简单的方法来测量MR，使用同卵和异卵双胞胎来确定MR的比率是否是遗传的，并最终确定MR的比率是否如我们预期的那样与癌症风险有关。

Cells in our bodies constantly sustain damage to their genetic material (genes) most of which is efficiently repaired. Some is not and accumulated damage to genes in a cell can start a cancer. There are several repair mechanisms that cells possess which have evolved since the earliest life-forms. One repair mechanism homologous recombination repair will, as a minor by-product of its activity, produce an event called mitotic recombination (MR). MR causes a loss of diversity of genes and this can contribute to cancer rather than prevent it. We have shown that the rate at which MR occurs varies very widely in humans. In this project we will devise a simple method for measuring MR, use identical and non identical twins to find if the rate of MR is inherited and finally see whether the rate of MR is associated with risk of cancer, as we expect.