LG 3.10 Genetics of Connective Tissue Disorders Flashcards
(33 cards)
The specific location of a coding sequence on a chromosome is known as what?
Locus or loci (plural)
When there is a mutation that affects a gene and results in an altered phenotype, what is the mutation affecting that leads to this change?
- Mutations lead to changes in transcription or translation, and eventually an abnormal (or no) protein product.
- These altered proteins is what results in the altered phenotype
Do all mutations alter proteins?
- NO!
- Genes have sequences upstream or downstream that influence their activity (promoters, inducers, etc.)
- Mutations in these sequences can dramatically change the action of the gene.
- They can change how the gene is transcribed or translated.
Do all mutations affect phenotypes?
- Not all.
- Some affect activity at the molecular level, but at the clinical level nothing is changed.
What is wt? What does it refer to?
- Wildtype
- Most common normal type around.
- Possibly a mutated phenotype but still most common and therefore wt.
- No “normal” allele, most common allele!
I am a carrier of Tay Sach’s but am totally normal, am I wt?
- Yes
- Wildtype is only based on phenotype
What does haplosufficient and insufficient mean when referring to loss of function mutations?
- Haploinsufficient: one allele is wiped out and this results in disease, the other good allele (only one) is not good enough. Dominant mutation.
- Haplosufficient: the other allele is prominent enough to take over control and no change is made. Recessive mutation.
What is a loss of function mutation? Is this a dominant or recessive change?
- Mutation that causes a protein to lose its function.
- Depends on haplosuffiency
What is a gain of function mutation when referring to a protein? Are these recessive or dominant mutation?
- Take a protein and give it new function
- “x-man” or “spider-man” mutation
- Dominant mutation, give new function
What is a dominant negative mutation?
- Abnormal function that interferes with the normal allele
- Sickle cell anemia: you have good hemoglobin and mutated hemoglobin, mutated hemoglobin interferes with the good and causes disfunction
What is a transition or transversion mutation?
- 2 base pairs switch
- Doesn’t matter the difference between them, he didn’t care
What is a missense mutation?
- Change one codon (base-pair) -> one amino acid change -> giant phenotype change
- Ex: sickle-cell
What is occurring in a nonsense mutation?
- Codon changes to a stop codon.
- Stops the translation of the protein -> usually leads to a nonfunctional protein.
What is a neutral mutation?
- Alters codons, alters amino acids
- Amino acids that change lead to no phenotypic change
- Neutral = no phenotypic change
What happens in a silent mutation?
- Base-pairs change
- Due to wobble-base pairing => no change in amino acid
What happens in a frameshift mutation?
- Add or subtract 1 base
- Add one = problem,, add two = problem,
add three = NEW AMINO ACID! - Protein becomes longer but no phenotypic change
Patient with muscular dystrophy is producing a dystrophin gene product that is missing 35 amino acids on its carboxyl end. Which mutation is the best candidate?
A) neutral B) missense C) nonsense D) frameshift E) silent
- Nonsense
Huntington’s disease is caused by a series of bases inserted into a gene. These are added in increments of 3, and add amino acids to the protein. The altered protein created is toxic to the cell. What best describes this type of mutation?
A) Loss of function
B) Gain of function
C) Dominant negative
- Gain of function mutation
If there is a disease or phenotype that is caused by any one of a number of mutations of an allele or a locus, what is this an example of?
- Genetic heterogeneity
What is the classic example of allelic heterogeneity?
- Cystic fibrosis, CFTR
- 2300 known mutant alleles for the CFTR gene that cause the disease phenotype
Explain the difference between allelic and locus heterogeneity.
- Many different genes code for a certain phenotype, mutations that occur in any of these genes at different chromosomal loci (locus heterogeneity) can cause the same disease state or phenotype.
- If there is one gene coding the phenotype, but you can get many different types of mutations in the allele that lead to the disease state, this is allelic heterogeneity.
Classic example of locus heterogeneity?
- Retinitis pigmentosa
- At least 35 loci mutations can create the phenotype
- These mutations can be both dominant and recessive
I have blood type B+, and you probably do not. This is a good example of?
A) allelic heterogeneity
B) locus heterogeneity
C) penetrance
D) expressivity
- Both allelic heterogeneity and locus heterogeneity
- Many different alleles for AB or O
- Plus or minus is controlled by different genes
What are some examples of stuff that is produced by fibroblasts?
- Collagen + elastin
