Ch 12 Gene Mutations Flashcards
Nature of mutations
Germaine or Somatic Cells
Germaine mutations: occurs in germs cells (egg or sperm)
You become multi-cellular by rounds of meiosis, which creates identical cells
- Originate in meiosis
- Affect all cells of an individual since that mutation exists in the single-cells zygote
Somatic cells mutations : are any non-sex cells are only passed onto those cells that undergo mitosis
Does not affect the individual as a whole
Ex. If I get skin cancer those tumor cells may be abnormal but my other tissues/ organs would not contain the acquired mutations
Mutation Vs Polymorphism
A mutation is change In a DNA sequence that is present in 1% of a population
Mutations Alter Proteins
Identifying how a mutation causes symptoms has clinical applications
Examples of mutations that cause disease:
- beta goo in gene
- collagen genes z
Sickle Cell Anemia
Autosomal recessive disorder that is common among African ancestry individual
Altered surface of hemoglobin allows molecules to link in low oxygen conditions
Adult hemoglobin is made up of 4 polypeptide chains 2 alpha and 2 beta
The 6th amino acid in the beta globin chain is supposed to be glutamic acid, which is a hydrophilic amino acid this position is exposed to water. A point mutation/base substitution causes valine to replace glutamic acid. Valine hydrophobic…. This causes multiple chains to aggregate together in an effort to place valine I the interior of a larger structure away from water.
Causes RBC to misshape into the sickle shape of RBC that get trapped in capillaries
They are only in circulation for a few week about instead of normal RBC’s 120 days
Sickling cause anemia, joint pain, and organ damage when RBC become logged in a small blood vessels
Beta Thalassemia
Caused by another beta hemoglobin mutation too few beta globin chains excess of alpha goblin prevent formation of hemoglobin molecules
So RBC’s die liberated iron slowly damages heart, liver and endocrine glands
Also affects the beta chain of hemoglobin sickle cell is one specific mutation , while beta thalassemia can be caused by various mutations within the gene
Effects can range from mild to severe depending if the mutation results in slightly abnormal chains to completely absent ones ( obviously, that’s worse!)
Thalassemia minor
Thalassemia Major
Collagen
Is the most abundant protein in your body
Triple helix structure the amino acid that is abundant within the helix inferior is glycine(which is the smallest amino acid replacing it with another amino acid causes deformation in the molecule )
A major component of connective tissue
-bone, cartilage, skin, ligament, tendon, and tooth dentin
More than 35 collagen genes encode more than 30 types of collagen molecules
Mutations in these genes lead to a variety of medical problems
Many exhibit genetic heterogeneity since multiple genes cb result in similar phenotypes
Depending on specific gene involved inheritance can either be dominant or recessive
Ehler-Danos syndrome
Extremely stretchy skin and easily dislocated joints (due to insufficient support )
Osteogenesis imperfecta
Brittle bones result in a multitude of breaks; some forms are fatal in uteri
Blue sclera (whites if your eyes) is common is some forms
Due to thinner than normal sclera, one can see the deeper pigmented layers of the eyeball
Spontaneous Mutation Rate
Are often due to just random error in replication
Point mutation a single letter error
Rate differs bet. genes
-Larger genes usually have higher mutation rates
Mitochondrial genes mutate at a higher rate the nuclear genes because they cannot repair their DNA
Mutational Hot Spots
Some genes are common site for random mutations
In some genes,mutation are more likely to occur in region called hot spots
Ex. Achondroplasia
Palindromes
-often associated with insertions or deletions are
Point mutation
Point mutation a change in a single nucleotide
Transition: purine replaces purine or pyrimidine replaces pyrimidine
A to G or G to A or
C to T or T to C
Transversion: purine replaces pyrimidine or pyrimidine replaces purine
A or G to T or C
T or C to A or G
Often classifies by result/ effect on gene product
Even though transversion mutations have more options, transition mutation are actually more common
This is due to the fact that transversion mutations involve bases of two different sizes- which make the error easier to detect for repair mechanisms
Consequences of Point Mutations
Silent
Missense
Nonsense
Silent
No change in sequence
Due to multiple codons coding for the same amino acid, even though the DNA sequence as been altered, the amino acid sequence has not
Missense
One amino acid is replaced by another
If the amino acid is similar size and chemical properties, this may not have a large phenotypic effect
Nonsense
Premature STOP codon is introduced
Results in a truncated (shortened) protein… Often non-functioning
Frameshift mutations
Either an insertion of additional bases or deletion of bases alters the reading frame and often affects the entire rest of the primary structure of the polypeptide
Unless in multiples of three…you can add or subtract amino acids at the mutation site, but the rest of the chain has the proper sequence
Expanding repeats
Some genes have some natural variations among individuals as to the number to repeated sequences are within a gene (CAG, for example, repeated over and over)
However, as that region increases in size, certain diseases occur due to instability of the gene product
Ex.Huntington disease
Huntington Disease
Autosomal dominant late-onset disorder that affects the CNS central nervous system
The increased number of repeats is correlated with severity of symptoms and age of onset (more repeats=more severe)
Due to instability during DNA replication, this region can actually increase in size
Ex. One copy of the gene might have 30 repeatss but during DNA replication in meiosis, I might pass 36 repeats in an egg this could result in a child having more severe symptoms than the parent
Cause if phenomenon of anticipation- severity increases earlier age of onset with successive generations
