[理学]6基因突变.ppt

上次复习 2010诺贝尔生理或医学奖 转座基因 细胞质遗传 叶绿体 三系法杂交水稻 线粒体 内共生学说 母性影响 第六讲 基因突变 第一节 基因突变的类型和效应 1. 体细胞突变（somatic mutation） 生殖细胞突变（germ-line mutations） 2, 转换（transition）是指同类碱基之间的替换。 颠换（transversion mutation）是嘌呤与嘧啶之间的替换。 4, 中性突变（neutral mutation）多肽链中相应位 点发生的氨基酸的取代并不影响蛋白质的功能; 5, 沉默突变（silent mutation）蛋白质中相应位点 是发生了相同氨基酸的取代，即同义突变。 6, 回复突变（reverse mutation）， 一类是正向突变（forward mutation）突变方向是从野生型向突变型；另一种是回复突变，其突变方向是从突变型向野生型 抑制突变（suppressor mutation）突变的作用还可以通过其它位点的突变而得到减少或校正。 8，Loss of Function Mutation results in a gene product with reduced or no function Loss of function Mutation affects the level of normal mRNA Frameshift causing premature termination codon Nonsense mutations Mutations in regulatory elements promoters, enhancers Mutation in a critical domain of protein, i.e ligand binding site of a receptor Loss of Function Tend to be recessive Cell functions normally with 50% of the gene product Occasionally dominant 50% not sufficient and haploinsufficiency produces abnormal phenotype Mutant polypeptide has lost its own function and interferes with the polypeptide of the normal allele - dominant negative effect Recessive Loss of function Waardenburg syndrome type I (WS1)An example of a dominant loss of function disease Clinical manifestations include hearing loss and pigment abnormalities of the hair, skin, and eyes.瓦登伯革氏 常染色体显性遗传性耳聋综合征 Molecular genetics of WS1 Caused by mutation in the paired-box 3 (PAX3) gene (chromosome 2q36.1) PAX3 protein is a transcription factor with three functional domains Gain of Function Mutation results in a gene product that does something positively abnormal Achondroplasia软骨发育不全 Short limbs, a normal-sized head and body, normal intelligence Caused by mutation in the FGFR3 gene Fibroblast growth factor receptor 3 Inhibits endochondral bone growth by inhibiting chondrocyte proliferation and differentiation Mutation causes the receptor to signal even in absence of ligand SBCs in splice si