章节大纲

  • 常规

    全部折叠 展开全部

  • 变异类型 - 高级

    lesson content

    Six fingers?
    ::六个手指?

    Obviously this is not very common. But it is not that uncommon, with an incidence of about 1 in 500 live births. Known as polydactyly, this phenotype has been associated with over 35 genetic mutations.
    ::这显然并不常见。 但这并不罕见,每500个活产中就有1个活产。 这种苯型被称作“混合活性 ” , 与超过35个基因突变相关联。

    Types of Mutations
    ::变音类型

    Mutations, a change in the or sequence, may have no effect, may be beneficial or may be harmful. There are numerous ways that the genetic information can be changed. Some of these changes can be inherited. In , mutations can be subdivided into germline mutations , which can be passed on to descendants, and somatic mutations , which cannot be transmitted to the next generation. Germline mutations change the DNA sequence within a or egg , and therefore can be inherited. This inherited mutation may result in a class of diseases known as a genetic disease. The mutation may lead to a nonfunctional , and the embryo may not develop properly or survive. Somatic mutations may affect the proper functioning of the cell with the mutation. During DNA replication , the mutation will be copied. The two daughter cells formed after will both carry the mutation. This may lead to the of many cells that do not function optimally, resulting a less than optimal phenotype. Various types of mutations can all have severe effects on the individual. These include point mutations , framehift mutations and chromosomal alterations . Keep in mind, some mutations may be beneficial or have no effect. Mutations that have no effect will not affect the expression of the gene or the sequence of amino acids in an encoded protein.
    ::突变、 变异、 变异、 变异、 变异、 变异、 变异, 可能没有效果, 可能有益, 也可能有害。 遗传信息可能会改变, 其中一些变异可以继承。 在突变中, 突变可以被细分为子宫突变, 并可以传给后代, 和体突变, 无法传给下一代。 Germline变异会改变一个或蛋的DNA序列, 并因此可以继承。 这种遗传变异可能会导致基因疾病一类。 突变可能导致不起作用, 胚胎可能无法正常发育或存活。 Somatic 变异会影响细胞与变异的正常功能。 在DNA复制过程中, 变异变会被复制。 后形成的两个女儿细胞将同时进行突变。 这可能导致许多细胞不发挥最佳功能, 导致一种比最佳的苯型。 各种变异种都会对个人产生严重影响。 这些突变点、 框架突变和染胚胎可能无法正常发展或存活。 保持某种基因变异的状态不会影响。

    Chromosomal Alterations
    ::染色体改变

    Chromosomal alterations are large changes in the structure. They occur when genetic material is added or removed from a chromosome. This alteration of a chromosome may occur when a section of a chromosome breaks and rejoins a chromosome incorrectly, or does not rejoin at all. Sometimes the segment may join backwards or reattach to another chromosome altogether. These mutations are very serious and usually lethal to the zygote or embryo. If the embryo does survive, the resulting organism is usually sterile and thus, unable to pass along the mutation.
    ::染色体的改变是结构结构的重大变化。当基因材料被添加或从染色体中去除时,就会发生染色体的改变。染色体的这种改变可能发生在染色体的某一部分断裂时,并错误地重新加入染色体,或者根本不重新加入。有时,染色体部分可能向后或重新加入到另一个染色体中。这些突变非常严重,通常对zygote或胚胎都致命。如果胚胎存活下来,由此产生的生物通常不育,因此无法通过突变过程。

    The five types of chromosomal alterations are deletions, duplications, insertions, inversions, and translocations ( Figure ).
    ::五类染色体改变是删除、重复、插入、倒置和转移(图)。

    1. Deletions are the removal of a large chromosomal region, leading to loss of the genes within that region.
      ::除去是清除一个大染色体区域,导致该区域内基因丧失。
    2. Duplications (or amplifications ) lead to multiple copies of a chromosomal region, increasing the number of the genes located within that region. Some genes may be duplicated in their entirety.
      ::重复(或放大)导致染色体区域的多份复制,增加了该区域内的基因数量,有些基因可能完全重复。
    3. Insertions are the addition of material from one chromosome to a nonhomologous chromosome.
      ::插入是指将一种染色体中的物质从一种染色体添加到一种非染色体中。
    4. Inversions are reversing the orientation of a chromosomal segment.
      ::逆向正在扭转染色体部分的方向。
    5. Translocations are the interchange of genetic material between nonhomologous chromosomes.
      ::移位是非混合染色体之间基因材料的交换。

    lesson content

    Chromosomal alterations. Deletion: the blue segment has been removed; Duplication: the blue segment has been duplicated; Inversions: the blue segment has been reversed; Insertion: the yellow segment has been removed from chromosome 4 and placed into chromosome 20; Translocation: a green segment from chromosome 4 has been exchanged with a red segment from chromosome 20.
    ::染色体改变 。 删除 : 蓝色部分已被删除 ; 重复 : 蓝色部分已被复制 ; 反转 : 蓝色部分已被倒转 ; 插入 : 黄色部分已从染色体 4 中删除, 并置于染色体 20 ; 移换 : 染色体 4 的绿色部分与染色体 20 的红色部分进行了交换 。

    Point Mutations
    ::点变数

    As the name implies, point mutations occur at a single site within the DNA. The example from : The (Advanced) concept demonstrates this mutation:
    ::正如名称所暗示的那样,点突变发生在DNA内的一个单一地点。

    THE BIG FAT CAT ATE THE RED RAT.
    ::巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型巨型雄

    A change at any one position could result in a sequence that does not make sense. Such as the C to A change shown here
    ::任何一个位置的改变都可能导致一个没有意义的序列。 如此处显示的 C 到 A 的更改

    THE BIG FAT AAT ATE THE RED RAT.
    ::巨型猫头鹰用红色鼠尾。

    As shown above, point mutations exchange one nucleotide for another and are known as base substitution mutations. These mutations are often caused either by chemicals or by a mistake during DNA replication. A transition exchanges a purine for a purine (A ↔ G) or a pyrimidine for a pyrimidine, (C ↔ T), and is the most common point mutation. Less common is a transversion , which exchanges a purine for a pyrimidine or a pyrimidine for a purine (C/T ↔ A/G). Point mutations that occur within the protein coding region of a gene are classified by the effect on the resulting protein:
    ::如上所示,点突变将一个核核素换成另一个核素,称为基替代变异。这些变异通常由化学物质或DNA复制过程中的错误造成。转基因交换纯(A G)或糖浆碘(C T),是最常见的变异点。转基因比较少见,转基因将纯素换成pyrimidine或pyrimidine(C/T A/G)。基因蛋白编码区域内发生的点突变对产生的蛋白质有影响:

    Type Description Example Effect
    Silent mutated codon codes for the same amino acid CAA (glutamine) → CAG (glutamine) none
    Missense mutated codon codes for a different amino acid CAA (glutamine) → CCA (proline) variable
    Nonsense mutated codon is a premature stop codon CAA (glutamine) → UAA (stop) usually serious

    These mutations may result in a protein with the same function, with altered function, or with no function. Silent mutations , as they code for the same amino acid, will have no altered effect on the protein. Missense mutations may have a minor effect or a dramatic effect on the protein. Nonsense mutations usually have the most dramatic effet. Depending on the position of the premature stop codon, nonsense mutations may result in an unstable mRNA that cannot be translated, or in a truncated mRNA and a much "smaller" protein without any significant activity.
    ::这些突变可能导致具有相同功能的蛋白质、功能改变或无功能的突变。 静态突变,如对同一氨基酸编码的静态突变,不会对蛋白产生任何改变效应。 密森色变异可能对蛋白产生轻微影响或戏剧性影响。 乱变通常具有最剧烈的偏差。 根据过早停止的codon的姿势,无谓的突变可能导致不稳定的 mRNA无法被翻译,或者在短短的 mRNA和大量“小”蛋白中,没有任何显著的活动。

    Deletions and Insertions
    ::删除和插入

    Similar to chromosomal alteration mutations, deletion or insertion mutations add or remove genetic information. Small deletions or insertions in the DNA will alter the reading frame . Deletions remove one or more nucleotides from the DNA, whereas insertions add one or more nucleotides into the DNA. These mutations in the coding region of a gene may also alter the splicing of the mRNA, known as a splice site mutation . Mutations which alter the reading frame are known as frameshift mutations . Splice site mutations and frameshift mutations both can dramatically change the mRNA, altering the final protein product.
    ::与染色体变异相似的突变、删除或插入突变会增加或删除遗传信息。在DNA中小幅删除或插入会改变阅读框架。删除会从DNA中去除一种或多种核素,而插入会将一种或多种核素添加到DNA中。基因编码区域的这些突变也可能改变 mRNA 的拼接,即被称为串联点变异。改变阅读框架的变异被称为框架变异。变异和框架变异都会显著改变 mRNA , 改变最终蛋白质产品 。

    Consider the following sequence of bases in RNA: AUG-AAU-ACG-GCU which is translated into start-asparagine-threonine-alanine.
    ::考虑在RNA建立以下一系列基地:AUG-AAU-ACG-GCU,该基地已转化为开始的paragine-threonine-aline-aline。

    Now, assume an insertion occurs in this sequence. Let’s say an A nucleotide is inserted after the start codon AUG :
    ::现在,假设在这个序列中插入一个插件。让我们假设一个核核酸在开始后插入到 AUG 之后:

    AUG-AAA-UAC-GGC-U is now translated into start-lysine-tyrosine-glycine.
    ::AUG-AAAA-UAC-GGC-U现在被转化成初期甘油。

    Even though the rest of the sequence is unchanged, this insertion changes the reading frame and thus all of the codons that follow it. As this example shows, a frameshift mutation can dramatically change how the codons in mRNA are read. This can have a drastic effect on the protein product.
    ::尽管其余的顺序没有变化, 但插入会改变读数框架, 从而改变随之而来的所有codon。 正如这个例子所显示的, 框架转换突变可以显著改变 mRNA 中的codon 是如何阅读的。 这可能会对蛋白质产品产生巨大影响 。

    Effect-on-Function Mutations
    ::功能效应变异

    For a cell or organism to maintain , the proteins work in a highly defined and regulated manner. It may take just one protein not working correctly to interrupt homeostasis. A protein having more or less activity than normal, or a different activity or function, may be enough to interrupt homeostasis. Mutations that may result in altered function of the gene product or protein are loss-of-function and gain-of-function mutations, as well as dominant negative mutations.
    ::对于细胞或生物体来说,蛋白质以高度界定和规范的方式发挥作用,只需一种不正确的蛋白质即可中断足部保持状态。一种或多或少活性超过正常状态的蛋白质,或一种不同的活动或功能,可能足以中断功能保持状态。可能导致基因产品或蛋白质功能改变的突变是功能丧失和功能增益,以及主要的负突变。

    Loss-of-Function
    ::职能损失

    Loss-of-function mutations result in a gene product or protein having less or no function. These mutations are usually recessive as a dominant normal gene can overcome the effects of the mutation. A null has a complete loss of function. This will result in reduced dosage (amount) of a normal gene product in heterozygous individuals. This reduced dosage may result in a normal phenotype. Haploinsufficiency results in when a reduced dosage of a normal gene product does not produce a normal phenotype. An example of a null allele is the O allele in the human A, B and O system. A and B refer to antigens on the surface of red blood cells . The alleles for the A-antigen and B-antigen are co-dominant; if both are present, then both are expressed resulting in type AB . The O blood type allele is a single base change mutated version of the A-antigen allele, resulting in no antigen expressed. As no protein product is produced, the allele for the O blood type is a null allele.
    ::功能丧失突变导致基因产品或蛋白质的衰减,功能较小或无功能。这些突变通常是消退性的,因为占支配地位的正常基因可以克服突变的影响。 无效者完全丧失了功能。 这将减少异体动物正常基因产品的剂量( 数量) 。 这种减少的剂量可能导致正常的苯型。 正常基因产品的剂量减少不会产生正常的苯型。 无效者的例子之一是人类A、B和O系统中的O allele。 A和B是指红血细胞表面的抗原。 A- antigen 和 B- antigen 的蛋白是同族的同族; 如果两者都存在, 两者都表现为AB 型。 O 血型所有元素都是单一的基变异变版本, 导致没有反基因。 由于没有生产蛋白质产品, O型血型的蛋白质是完全无效的。

    Gain-of-Function
    ::益 益 益

    Gain-of-function mutations result in the gene product or protein having a new and abnormal function and usually result in a dominant phenotype. Examples of gain of function mutations occur in the thyroid receptor gene.
    ::功能增益突变导致基因产品或蛋白质具有新的和不正常功能,通常产生占支配地位的苯型,功能突变的例子出现在甲状腺受体基因中。

    The thyroid hormones, triiodothyronine (T3) and thyroxine (T4), are necessary for maintaining an appropriate basal metabolic rate and affect essentially every tissue in the body. They are produced by the thyroid gland . Production of these hormones is stimulated by thyroid stimulating hormone (TSH), a glycoprotein secreted by the pituitary gland in the brain . TSH binds with the TSH receptor on the surface of the cells of the thyroid gland, initiating a series of biochemical events that result in an increase in circulating thyroid hormones, which have numerous effects. T3 and T4 levels are maintained by a negative feedback loop mechanism. Mutations within the gene coding for the TSH receptor can result in problems for the body in controlling thyroid hormone levels. Gain-of-functions mutations in the gene for the TSH receptor result in the receptor being constitutively active, or "switched on," even in the absence of TSH. These mutations result in more thyroid hormone produced, resulting in the inability to maintain homeostasis and detrimental phenotypes. A number of loss-of-function mutations have also been identified in the TSH receptor gene.
    ::甲状腺激素(TH)和甲状腺激素(T4)是保持适当的巴萨新陈代谢率并从根本上影响人体每个组织的必要条件。这些激素是由甲状腺腺生成的。这些激素的生产受到甲状腺刺激激素(TSH)的刺激,一种由脑中垂死腺分泌而分泌的甘醇。TSH在甲状腺细胞表面与TSH受体捆绑在一起,引发一系列生物化学事件,导致甲状腺激素循环增加,产生多种影响。T3和T4水平由负反馈环机制维持。TSH受体基因编码中的突变可能导致身体在控制甲状腺激素水平上出现问题。TSH受体基因的功能变异导致受体活跃或“变异”,即使在没有TSH的情况下,这些突变体也会导致更多的甲状腺激素产生更多的甲状腺激素,因此无法保持家庭致变的基因。

    Dominant Negative
    ::最大负负

    Dominant negative mutations have an altered gene product that acts in a dominant manner to the wild-type gene product in the same cell. These two gene products often dimerize (combine) to make the protein. Often the effects of such a mutation result in an inactive gene product. Dominant negative mutations are often more harmful than null alleles. Examples of dominant negative mutations occur with the collagen genes.
    ::显著负突变的基因产品被改变,以主导同一细胞中的野生基因产品。这两种基因产品往往使蛋白质分解(combine ) 。这种突变的影响往往导致非活性基因产品。显著负突变往往比无源异变更有害。主要负突变的例子出现在科兰基因中。

    Type II collagen is the preeminent protein in cartilage . The protein forms from three gene products of the gene for type II collagen, COL2A1 . Mutations in the COL2A1 gene result in a phenotypic spectrum of disease, ranging from primatial lethal to comparatively moderate phenotypes. The collagen protein is a trimer of three polypeptides . A COL2A1 null allele will result in decreased amounts of normal collagen polypeptides produced. Decreased amounts of the collagen protein result in a mild phenotype compared to phenotypes that result from a dominant negative mutation. Half normal and half mutant polypeptides produced combine to form almost all abnormal collagen protein product. As the cartilage with this abnormal protein is the precursor to formation, this process is hindered, and these children have severe phenotypes. Some mutations lead to death in utero . Similar dominant negative mutations are characteristic of the type I collagen disorders and the Osteogenesis Imperfecta phenotypes, which are also known as Brittle-Bone sides.
    ::II型科洛兰蛋白是软骨中最突出的蛋白质。二型科洛兰基因、COL2A1基因的三个基因产物的蛋白质形式为二型科洛兰基因的三种基因,COL2A1基因的突变导致一种小类疾病,从初等致命到相对中度的酚型。科洛兰蛋白是三种聚苯酯的三倍数。COL2A1 空心灵将会导致正常的科洛兰蛋白聚苯酯的产量下降。科洛兰蛋白的含量下降,导致轻微的苯型与主要负变异导致的苯型相比出现轻微的苯型。所生产的半正常和半变异异异聚苯并形成几乎所有异常的科朗蛋白蛋白蛋白产物。由于使用这种异常蛋白蛋白作为形成前体,这一过程受到阻碍,这些孩子有严重的苯型。一些突变导致子在子宫内死亡。类似的主要负突变种是I型科兰根紊乱症和奥氏成型苯型的特征,这些也是人们所熟悉的一等。

     

     

    Summary
    ::摘要

    • Germline mutations can be passed on to descendants; somatic mutations cannot be transmitted to the next generation.
      ::血细胞突变可以传给后代;体细胞突变不能传给下一代。
    • Chromosomal alterations are large changes in the chromosome structure. There are 5 types of chromosomal alterations: deletions, duplications, insertions, inversions, and translocations.
      ::染色体改变是染色体结构的重大变化,有5种染色体改变:删除、重复、插入、倒置和移位。
    • Point mutations occur at a single site within the DNA; examples of these include silent mutations, missense mutations, and nonsense mutations.
      ::DNA内单一地点发生点变异;这些变异的例子包括静音变异、兆子变异和无稽变异。
    • A deletion or insertion in the DNA can alter the reading frame.
      ::删除或插入DNA可以改变阅读框架。
    • Loss-of-function and gain-of-function mutations may result in altered function of the gene product or protein.
      ::功能丧失和功能获得突变可能导致基因产品或蛋白质的功能改变。

    Review
    ::回顾

    1. Identify three types of chromosomal alterations.
      ::查明三种染色体变化。
    2. Distinguish among silent, missense, and nonsense point mutations.
      ::区分沉默, 小姐, 和无稽之谈 点突变。
    3. What is a frameshift mutation? What causes this type of mutation?
      ::什么是轮廓变异?什么是这种变异的原因?
    4. Assume that a point mutation changes the codon AUU to AUC. Why is this a neutral mutation?
      ::假设一个点变异 将AUAU改变为AUC。为什么这是中性变异?
    5. Look at the mutation shown here. The base A was inserted following the start codon AUG. Describe how this mutation affects the encoded amino acid sequence: AUG-GUC-CCU-AAA → AUG-AGU-CCC-UAA-A.
      ::看看这里显示的突变。 基地 A 是在启动 AUG 后插入的。 描述这种突变如何影响编码的氨基酸序列: AUG- GUC- CCU- AAA AA AUG- AGU- CCC- UAAA- AAA AUG- AGU- CCC- AAAA 。
    6. Compare and contrast germline mutations and somatic mutations.
      ::比较和对比子系突变和体突变