Mutations Flashcards
What are mutations?
- any change to the nucleotide sequence of DNA has the potential to alter the amino acid sequence of a protein
- also, a mutation in DNA regulatory sequences can alter the expression of the gene
- mutations in RNA processing signals can alter mRNA sequence or stability
- in any of these cases, the normal cellular expression of the protein may be compromised
**only mutations in germ cells will be inherited
Not all mutations are bad
- some are the basis for evolution and for refinement of protein function
- some provide medical benefit
What is the major cause of some large scale mutations?
radiation in our environment
What are the four major forms of large scale mutations?
- deletions
- inversions
- insertions
- translocations
Deletions
- generally caused by uneven crossing over during meiosis or DNA breaks from radiation - natural radiation or medical X-rays
- a deletion can include many different genes
- often occurs when DNA is physically broken (possibly by above methods) and then rejoins (and that middle section is degraded
Human disease associated with chromosomal deletion:
Chromosome 22q11 deletion syndrome
- aka Catch-22, di George, or Velocardiofacial syndrome
- symptoms: heart defects, cleft palate, and autism
- ~1 in 4000 births
- most commonly involves loss of about 3 million base pairs (and about 30 genes) from one copy of chromosome 22 (i.e. heterozygous)
- 93% of cases are de novo (new mutation not inherited from parents) deletions
Inversions
- sometimes DNA breaks or recombination events may result in inversions
- a rejoin event in the middle of a gene can be disastrous
- however, if entire gene is contained in a large enough inversion, the gene may continue to function normally
- basically, all DNA sequences are still present in chromosome, but they are in the wrong orientation
*inversions are quite common and can be completely harmless
Ex: A-B-/-C-D-/-E-F (/ = break)
inverted: A-B-D-C-E-F
Inversions may not have any consequences; remember the lysozyme gene
- it is surrounded by very long stretches of non-essential DNA
- it could easily be contained within an inversion without any problems
Human disease associated with chromosomal inversion:
Hunter syndrome
- loss of function of an enzyme, iduronate-2-sulfatase (I2S), that degrades glycosaminoglycans (GAGs), which are long polymers of sugar
- build-up of GAGs leads to heart disease, restricted airways, enlargement of liver and spleen
- most common in males because gene is on X-chromosome
- mutation results from inversion recombination event between the functional I2S gene and its inactive pseudogene
Insertions
- insertions of sequences up to several thousands of bases long may be caused by DNA breaks or by transposons and retroviruses
- insertions into coding or regulatory regions may completely destroy gene function
- we have previously discussed insertion of LINEs into the factor VIII and factor IX genes resulting in hemophilia
Insertion mutation disease
Hemophilia
insertion of LINEs into the factor VIII and factor IX genes
Translocations
- genetic material is interchanged between two chromosomes
- huge amounts of DNA can be involved, but major disruption occurs at the join point
- if translocation occurs in the coding or regulatory region of a gene it may disrupt normal gene function
looks like: green sister chromatid chromosome, Red chromosome –translocation–> tip of one green exchanges with tip of red
Burkitt’s Lymphoma is caused by what mutation?
Translocation
Human disease associated with translocation:
What is Burkitt’s Lymphoma?
- cancer of lymphocyte cells
- the c-myc proto-oncogene on chromosome 8 is translocated adjacent to the immunoglobulin heavy chain region on chromosome 14
- because the Ig genes are extremely active in lymphocytes, this activates the myc gene in these cells and contributes to malignancy
What are the different types of point mutations?
- mis-sense
- non-sense
- frame shift
