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Gene Expression / Mutations
The fifth type of mutation is the translocation, the transfer of a piece of chromosome to a nonhomologous chromosome. They are often reciprocal; the two nonhomologues switch segments. The effects of translocations on the phenotype include that the break may be within a gene, destroying its function. These genes may be under the influence of different promoters and enhancers, changing their expression. One such example is in Burkitt's Lymphoma, a solid tumor of B lymphocytes. Another effect is that the breakpoint may occur within a gene, creating a hybrid gene.
So what exactly causes all these various types of mutations? There are many factors that contribute to mutations: chemical mutagens, radiation (x-rays, gamma rays, UV), and transposable elements. How are these known? By measurements. Mutation rates can be measured by one of three ways: directly observing the changes from one genotype to another, measuring substitution rates with the assumption of selective neutrality, or accumulating mutations over many generations to magnify the effects. These methods have led scientists to conclude the following number of mutations per generation, although they may vary tremendously from gene to gene, individual to individual, species to species:
Per base pair ~10-8 - 10-9
Now that it is known how to measure the rates of mutations, how often do they occur? Surprisingly, mutations are actually rare. Humans inherit 3 x 109 base pairs of DNA from each parent. As seen above and just considering single-base substitution, this means that each cell has 6 billion (6 x 109) different base pairs that can be the target of a substitution! Single-base substitutions are most apt to occur when DNA is being copied; for eukaryotes this is during S phrase during the cell cycle. In humans and other mammals, uncorrected errors (= mutations) occur at the rate of about 1 in every 50 million (5 x 107) nucleotides added to the chain. But with 6 x 109 base pairs in a human cell, that mean that each new cell contains some 120 new mutations. However, most (as much as 97%) of our DNA does not encode anything. This includes repetitive or "junk" DNA, non-coding DNA in introns and flanking structural genes. Even in coding regions, the existence of synonymous codons may result in the altered gene still encoding the same amino acid in the protein.
Since most mutations occur in the S phase of the cell cycle, males are more at risk than females are. This is because only two dozen (24) or so mitotic divisions occur from the fertilized egg that starts a little girl's embryonic development and the setting aside of her future eggs (which is done long before she is even born). Also, The sperm of a 30-year old man, in contrast, is the descendant of at least 400 mitotic divisions since the fertilized egg that formed him. Therefore, fathers are more likely than mothers to transmit newly-formed mutations to their children. In addition, the children of aged fathers suffer more genetic disorders than those of young fathers suffer.
So what is the significance of a mutation? It is influenced by the distinction between germline and soma. Mutations that occur in the somatic cell (such as the bone marrow or liver) may either damage, kill, or make the cell cancerous. The somatic cell mutation will eventually disappear when the cell itself dies. In contrast, germline mutations are found in every cell descended from the zygote to which that mutant gamete contributed. If an adult is successfully produced, every one of its cells will contain the mutation. Included among these will be the next generation of gametes, so if the owner is able to become a parent, that mutation will pass down to yet another generation. Thus, it can be seen that mutations are a failure of DNA repair.
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