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.