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1、,微测验No.1 进入医学遗传联盟公众号 “消息发布”栏目 微测验 输入密码并开始测验,5min后关闭,密码:2378,03 基因突变Gene Mutation,Gene Mutation Mutations are heritable changes in genetic material. Change in genes caused by change in structure of the DNA.,Base(s) in DNA is (are) changed to other(s), or a base(s) is (are) added or removed. Rearrange
2、ments of the chromosomes occur and are also considered.,多向性 重复性 随机性 稀有性 可逆性 forward mutation, reverse mutation 有害性,1. Mutagens or Mutagenic Agents,Mutations can occur at a spontaneous rate (spontaneous mutation), or a far greater rate when there is exposure to mutagenic agents (induced mutation).,Th
3、ese are substances, conditions and forms that significantly increase the frequency of mutations.,Mutagens,Exposure to too high a level of mutagens can threaten the survival of a species; e.g., frog species in the states of Washington and Oregon are facing extinction. This appears to be caused by red
4、uced atmospheric ozone, and the resulting increased level of ultraviolet radiation.,A forms of energy Examples of a forms of energy are ultraviolet light, x-rays, cosmic energy, gamma radiation, alpha particles, beta particles and neutrons.,Ultraviolet (UV) light UV light has shorter wavelengths tha
5、n visible light. Though these waves are invisible to the human eye, some insects, like bumblebees, can see them!,Scientists have divided the ultraviolet part of the spectrum into three regions: the near ultraviolet, the far ultraviolet, and the extreme ultraviolet.,The three regions are distinguishe
6、d by how energetic the ultraviolet radiation is, and by the wavelength of the ultraviolet light, which is related to energy.,UVA UVB UVC,The near ultraviolet, abbreviated NUV, is the light closest to optical or visible light. The extreme ultraviolet, abbreviated EUV, is the ultraviolet light closest
7、 to X-rays, and is the most energetic of the three types. The far ultraviolet, abbreviated FUV, lies between the near and extreme ultraviolet regions.,Ultraviolet Radiation causes pyrimidine dimers(嘧啶二聚体). These can block DNA replication. Also, dimers interfere with base pairing between the two DNA
8、polymeres. U.V. light also generates free-radicals, which create other kinds of genetic damage.,Radiation（Gamma and X-Rays） These can act directly on DNA; also，damage is caused indirectly when molecules around the DNA such as water, are ionized, creating free-radicals, substances with unpaired elect
9、rons.,Most often, the result is single or double stranded breaks in the DNA molecules. These breaks are hard to repair.,B Chemical Agents Examples of substances that are mutagens are ： nitrous acid（亚硝酸） hydroxylamine（羟胺） Alkylating agents (烷化基) 5-bromouracil（5-溴尿嘧啶，5-BU） benzo (a) pyrene acridine dy
10、es（吖啶）,Hydroxylating agents (hydroxylamine，HA) （羟胺）,Nitrous acid is a deaminating agent. （亚硝酸）,图中A被其脱去氨基后可变成次黄嘌呤（H），H不能再与T配对，而变为与C配对，经DNA复制后，可形成T-AC-G的转换。,Alkylating agents (烷化基) Alkylating agents are chemicals that donate alkly groups to other molecules. Ethyl methanesulfonate (EMS,甲烷磺酸乙酯 ) methyl
11、aldehyde（甲醛） Caryolysine（氮芥）,GC-T-A,Base analogs Base analogs are similar to the actual correct base and so get incorporated into the DNA as would its natural counterpart. The problem is that, if they are more prone to tautomeric shifts than the natural base, the frequency for mutation goes up, subs
12、tantially. The compound 5-bromouracil is an example of an analog to thymine. It undergoes a tautomeric shift to base pair with guanine instead of adenine, causing a transition.,5-BU引起的DNA碱基对的改变 5-BU与腺嘌呤（A）和鸟嘌呤（G）均可配对。如果5-BU取代T以后一直保持与A配对，所产生的影响并不大；若与G配对，经一次复制后，就可以使原来的A-T对变换成G-C对。,N-二甲基亚硝胺,Viruses、Eum
13、ycete、Bacteria Viruses that can integrate into the genome are also mutagenic agents fungally contaminated peanuts or peanut butter, and many, many more,2. Mechanism of Mutation,Static mutation Dynamic mutation,Static mutation Microalterations Macroalterations,Microalterations involve single base pai
14、r. Point mutation base substitution Transitions（转换）: Purine changes to an alternate purine; pyrimidine changes to an alternate pyrimidine. Transversions(颠换): A position with a pyrimidine changes to have a purine; or, purine to pyrimidine,Transitions occur more commonly than transversions even though
15、 more theoretical combinations of transversions are possible. For example, the only possible transition for the base A is to change to the base G. Two transversions are possible for the base A: C and T.,Frameshift mutation Frameshift mutations are the result of a single base, or more, insertion or d
16、eletion.,Macroalterations are large changes, such as duplications, deletions, inversions or rearrangements of a large number of bases.,Dynamic mutation The term dynamic mutation was introduced to distinguish the unique properties of expanding, unstable DNA repeat sequences from other forms of mutation. Trinucleotide repreat expansion The past decade has seen dynamic mutations uncovered as the molecular basis for a growing nu
