Gene and Chromosomal Mutations

Study Notes

Mutations are heritable alterations in a gene or chromosome.
They involve permanent changes in the nucleotide sequence of an organism's genome, a virus, or other genetic elements.
Mutations can be beneficial, neutral, or detrimental to the organism.

Origin:
- Spontaneous mutations: Occur in the absence of known mutagens.
- Induced mutations: Occur in the presence of known mutagens.
Mutagens: Agents that increase the rate of mutation. Examples include bromine, benzene, X-rays, and UV radiation.
Cell Type:
- Somatic mutations: Occur in non-reproductive cells and are not passed to the next generation.
- Germ-line mutations: Occur in reproductive cells and can be passed to the next generation.
Expression:
- Conditional mutations: Expressed only under restrictive conditions (e.g., high temperatures).
- Unconditional mutations: Expressed under permissive as well as restrictive conditions.
Effect on Function:
- Loss-of-function (knockout/null): Complete gene inactivation or non-functional product. Example: deletion of all parts of a gene.
- Hypomorphic (leaky): Reduces, but doesn't eliminate, gene expression or product activity. Example: Nucleotide substitution reducing transcription level.
- Hypermorphic: Produces a greater than normal level of gene expression.
- Gain-of-function: Qualitatively alters gene action. Example: A gene becoming active in a cell type where it's not normally active.

Base Substitution: Replacement of one base pair with a different base pair, potentially causing a temporarily mismatched base pair.
Transition: Replacement of one pyrimidine base with the other pyrimidine base or one purine base with the other purine base. Possible transitions include T-C or C-T, and A-G or G-A.
Transversion: Replacement of a pyrimidine base with a purine base, or vice-versa. Examples of transversions: T-G, C-G, A-C, and G-T.
Insertion: Addition of one or more nucleotides.
Deletion: Removal of one or more nucleotides.

Synonymous Substitution (Silent): Mutations in nucleotide sequence, but don't change the amino acid sequence.
Missense: Changes in nucleotide sequence to alter the amino acid sequence. Example: A C-G base pair is replaced by T-A. This resulted an amino acid changed from Arginine to Tryptophan.
Nonsense: Create a new STOP codon, often resulting in loss of gene function. Example: UGG (Try) to UGA (Stop).
Frameshift: Shifts the reading frame of codons, affecting the sequence of amino acids, leading to potentially significant changes in the protein product. This can be from deletion or insertion.

Structural Chromosomal Mutations:
- Deletion: Loss of a portion of DNA.
- Duplication: Production of an extra copy of a DNA region.
- Inversion: Reversal of a chromosome segment. Pericentric inversions involve the centromere, while paracentric ones do not.
- Translocation: A fragmented chromosome joins with a non-homologous chromosome, with new segment detach. Reciprocal translocation is the exchange between two different chromosomes. Robertsonian translocation involves the joining of two q arms of two different chromosomes.
Chromosomal Number Mutations:
- Euploidy: Normal number of complete chromosome sets. (x or 2x).
- Aneuploidy: Abnormal number of chromosomes (2n-1, 2n+1, 2n+2...). Monosomy (2n-1, losing a chromosome), Trisomy (2n+1, gaining a chromosome), Tetrasomy (2n+2, gaining two chromosomes), Nullisomy (2n-2, losing two chromosomes).
- Polyploidy: Having three or more sets of chromosomes (e.g., triploidy, tetraploidy).

Survival: Mutations help individuals adapt to their environment, and are an important force in evolution. They help balance out the frequency of alleles. Examples include malaria resistance and lactose intolerance.
Diversity: Genetic diversity is essential for evolutionary change.

Genetic Disorders: Mutations can cause a wide range of genetic disorders that can be severely detrimental.
Other Diseases: Some mutations can trigger other diseases like cancer, such as lung, breast, and bladder cancer.