精神疾病遗传动物模型的现状与展望

精神障碍是一类高度遗传的多基因复杂性疾病,其中精神分裂症、孤独症以及双向障碍等疾病的遗传率可达80％,抑郁症以及神经性厌食等具有中等程度的遗传率,约为40％ ～ 60％[1].大多数精神疾病的产生系多个致病基因变异所致,通常人们认为,很多常见变异(common variants)对诱发疾病只产生一些微小的效果,这些单个基因本身并不足以导致疾病的发生,但是,当这些基因的效果共同叠加在一起时,就会超过机体所能承受的阈值而导致发病.到目前为止,研究者已经在发现和筛查这些常见基因变异方面取得了重要的研究成果.除此之外,研究者在一些精神疾病中还发现了所谓罕见的、具有中等危险性的变异基因,例如,精神分裂症在几个染色体上的拷贝数变异(CNVs)等.然而,据推测,这些常见变异以及具有中等危险程度的CNVs在精神分裂症中只能解释不到10％的遗传性[1],对其他遗传效果如罕见点变异(rare point mutations)、罕见拷贝数变异,特别是非线性的遗传效果,如基因与基因之间的相互作用、表观遗传因素以及基因与环境的相互作用的影响等研究,目前还处于刚刚起步的阶段.

恶性疟在抗药性时期

Ant malarial drug resistance exists when adequate drug blood concentration are to kill a previously susceptible parasite. This occurs by evolutionary selection of spontaneously arising mutant parasites that aredrug insensitive. Drug resistance is often, but not always, due to point mutations that change drug accumulation/effiux in the erythrocyte or reduce affinity for target molecule. Drug resistance can present in several ways to include: failure of treatment to clear parasites in a single patient, increase in malaria prevalence, malaria occurring in areas where it had not been seen recently such as epidemic malaria.

OBJECTIVE To study the structural and preliminary functional characterization of the hepatitis B virus(HBV) enhancer Ⅰ in patients with chronic hepatitis B treated with interferon (IFN). METHODS The characteristics of the HBV enhancer Ⅰ in 12chronic carrier who were treated with alpha interferon was detected by the methods of molecular biology including PCR, cloning of PCR products, sequencing and cell culture.RESULTS Four of 6 patients cleared viral DNA; all 6 in this group also seroconverted from e antigen to antibody. Prior to therapy, the HBV enhancer Ⅰ region demonstrated many point mutations in all 6 patients who became nonresponders, compared to patients who responded to interferon. The mutated sequences, many of which were within regions of transcription factor binding, were significantly more active than the corresponding wild type sequences in reporter gene assays. CONCLUSION These results imply that the mutations found in nonresponders appear to render the virus less sensitive to interferon.