Expansion of the CGG repeats to such a degree results in a methylation of that portion of the DNA, effectively silencing the expression of the FMR1 protein.
Inheritance of Fragile-X syndrome.
自发突变的分子基础
DNA复制错误引起的基因突变
自发化学改变引起的基因突变 (碱基脱嘌呤 (depurination)、脱 氨基 (deamination)
自发化学改变引起的基因突变(碱基脱 嘌呤 (depurination)、脱氨基 (deamination)
转座因子及插入序列引起的基因突变
重组错误
在DNA复制中由于互变异构移位所产生的突 变
在DNA复制中由于碱基的错误跳格自发产生碱基的插入和缺失
在DNA复制中由于碱基的错误跳格 自发产生碱基的插入和缺失
Mutation of the FMR1 gene leads to the transcriptional silencing of the fragile Xmental retardation protein, FMRP. In normal individuals, FMRP binds and facilitates the translation of a number of essential neuronal RNAs. In fragile X patients, however, these RNAs are not translated into proteins.
由于DNA复制中跳格所引起的E. coli lacI基因中的4碱基CTGG热点突变
脆性X染色体综合症 (Fragile-X syndrome)
The fragile X syndrome is a genetic disorder caused by mutation of the FMR1 gene on the X chromosome. Normally, the FMR1 gene contains between 6 and 55 repeats of the CGG (trinucleotide repeats) in the 5’UTR. In people with the fragile X syndrome, the FMR1 allele has over 230 repeats of this codon.
遗传学课件第10章 基因突变
variation
变异：亲代与子代或群体内不同个体间 基因型或表型的差异
……
突变：基因的结构发生改变而导致细胞
mutation
或生物体的基因型发生稳定的可遗传的 变化的过程
chromosomal aberration
gene mutation or point mutation
mutation)
a →A
抑制因子突变(suppressor mutation): intragenic或intracistronic suppressor extragenic或extracistronic suppressor
p249
突变的分子基础
自发突变的分子基础
DNA复制错误引起的基因突变
(base-pair substitutions) 移码突变
(frameshift mutation) 缺失突变
(deletion mutation)
不 同 类 型 基 因 突 变 产 生 不 同 构 型 和 活 性 的 蛋 白
正向突变(forward mutation) A→a
回复突变(reverse mutation或back
null mutation(无效突变)：完全丧失基因功能 的突变。
leaky mutation(渗漏突变)：指仍能部分表达 (残余水平）原先活性的突变。
spontaneous mutation induced mutation
根据DNA发生改变的情况，有下列突变 方式ຫໍສະໝຸດ 以改变基因的信息内容：碱基替换
epigenetic variation：亲代与子代或群
体内不同个体间非基因型突变的表型差异。
基因突变的类型
体细胞突变（somatic mutation）：是不能 遗传给后代的，但是可以通过无性途径传递。
生殖细胞突变（germ-line mutation）：若 突变的性细胞参与受精过程，那么突变基因 就会传给下一代。
How is Fragile-X syndrome inherited? An altered gene on the X-chromosome causes Fragile-X syndrome. A girl will normally have a working gene on her other X-chromosome, which partially makes up for the altered gene, so girls are usually less severely affected than boys. The genetic change in Fragile-X is very unusual; it tends to change between parent and child, so predicting the exact risk of having an affected child is complicated.
This methylation of the FMR1 locus in chromosome band Xq27.3 is believed to result in constriction of the X chromosome which appears 'fragile' under the microscope at that point, a phenomenon that gave the syndrome its name.