Mutations
المؤلف:
Bezabeh ,M. ; Tesfaye,A.; Ergicho, B.; Erke, M.; Mengistu, S. ; Bedane,A. and Desta, A
المصدر:
General Pathology
الجزء والصفحة:
21-2-2016
1381
Mutations
- are the bases of genetic diseases.
- are defined as permanent changes in the primary nucleotide sequence of DNA regardless of its functional significance.
- occur spontaneously during cell division or are caused by mutagens such as radiation, viruses, & chemicals.
- can occur in germ line cells (sperm or oocytes) or in somatic cells or during embryogenesis. Germline mutations can be passed from one generation to the next & thus cause inherited disease. Somatic mutations do not cause hereditary disease but they may cause cancer (because they confer a growth advantage to cells) & some congenital malformations. Mutations that occur during development (embryogenesis) lead to mosaicism. Mosaicism is a situation in which tissues are composed of cells with different genetic constitutions. If the germ line is mosaic, a mutation can be transmitted to some progeny but not others. This can sometimes lead to confusion in assessing the patterns of inheritance.
- affect the various levels of protein synthesis.
- can be classified into the following three categories based on the extent of the genetic damage:
2. Genome mutations
- are due to chromosome missegregation.
- are gain or loss of one or more whole chromosomes.
- are exemplified by aneuploidy & polyploidy.
- are often incompatible with survival.
3. Chromosome mutations
- are due to rearrangement of genetic material in a chromosome which results in structural changes in the chromosome.
- can be seen by the microscope.
- are exemplified by translocations.
- are infrequently transmitted because most are incompatible with survival (like genome mutations).
4. Gene mutations
- cause most of the hereditary diseases.
- are submicroscopic (i.e. cannot be seen by the microscope).
- may affect a single base (more common) or they may affect a larger portion of a gene.
- have the following types:
A. Single base pair change (Point Mutation)
B. Deletions & Insertions
C. Expansions of repeat sequences
Summary:-
- Mutations can interfere with normal protein synthesis at various levels:-
1. Promoter/enhancer mutations → No transcription/ increased transcription → No protein/increased protein.
2. Missense mutation → Abnormal protein with a different amino acid → A protein altered with function or loss of function
3. Nonsense mutation → Affects translation → Truncated protein → Rapidly degraded protein → Absence of the protein.
Many different proteins are synthesized in each cell of the body. These proteins include enzymes & structural components responsible for all the developmental & metabolic processes of an organism. Mutation can result in abnormality in any of these protiens.
Mutation → Abnormal protein/No protein/ Increased protein → Abnormal metabolic processes → Tissue injury →Genetic diseases.
References
Bezabeh ,M. ; Tesfaye,A.; Ergicho, B.; Erke, M.; Mengistu, S. and Bedane,A.; Desta, A.(2004). General Pathology. Jimma University, Gondar University Haramaya University, Dedub University.
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