Genetics Flashcards
The specific location of a coding sequence on a chromosome is known as what?
locus
Do all mutations affect the phenotype in a clinical sense?
no.
Molecularly speaking yes, but using a clinical definition where many mutations are unrelated to a disease state this is not true.
The most common allele would be considered what? This designation is based on what; clinically speaking?
wild type
Based on whether the person has an observable phenotype that is suggestive of the wild type, even if they are a disease carrier and not homozygous for a non disease state, but only appear to be.
WT= PHENOTYPE NOT GENOTYPE!!!!
What are some mechanisms for dominant and recessive genotypes?
Loss of function- usually recessive. If the reduced activity of one allele leads to loss of function this haploinsufficient and is dominant, but if only the loss of both alleles leads to a loss of function this is recessive. The loss of one of these alleles would not lead to loss of function and would be considered haplosufficent.
Gain of function- novel action is gained
Dominant negative mutation- where the abnormal function of one allele interferes with the normal function of another allele. I.E. sickle cell, where Hb-S bind to Hb-A.
What’s a missense mutation? why is it important and where does it typically occur?
mutation resulting in a AA change. It’s important for protein structures and can potentially cause loss of function of the protein. It typically occurs on the first base pair of a 3 pair set, where the degenerate nature of DNA isn’t as useful. I.E. sickle cell one base pair change.
What’s a neutral mutation; silent?
Neutral- changes AA, but no real protein structural change occurs and no phenotypic change would be observed clinically
Silent- degenerate codon takes care of these, as AA can be made by more than one 3 bp code.
Huntington’s disease is caused by a series of bases inserted into a gene. These are added in increments of 3 (repeats), and add AA to the protein. The altered protein created is toxic to the cell. What best describes this type of mutation?
If these repeated bases are added in each generation and cause a more rapid disease state how would you describe this?
Gain of function mutation
The protein grew in size and then had a new effect (toxic) and although the function gained is deleterious, it is a new/gained function
Genetic anticipation.
You have a patient that has a recent genetic screen for the zombie x phenotype. It’s believed that this stems from a single gene mutation resulting in various phenotypes of aggression depending on the location of the mutations on the gene. As your exploring this phenomenon in the lab you discover that there are actually 3 genes involved that each result in the same zombie x phenotype.
How would you describe this latter discovery?
A) genetic anticipation
B) Allelic heterogeneity
C) Locus Heterogeneity
D) pleitropy
The latter discovery is locus heterogeneity (mutations at different loci) the former is allelic heterogeneity.
Locus heterogeneity is problematic because it’s difficult to see all of the various genes that contribute to the overall disorder that is observed. Cancer is an example of many genetic abnormalities resulting in uncontrolled growth etc.
Classic allelic= Cistic fibrosis CFTR
Your friend who just won the US 100m dash in the Athens Olympics was just diagnosed with cistic fibrosis when it was observed clinically that he lacks a vas deferense making him sterile. He’s never had trouble breathing in his life; is his world renown doctor wacked? What genetic process is at play here?
No he’s world class for a reason. This is an example of loci heterogeneity. The more research that’s done on cistic fibrosis the more loci will likely be discovered that are associated with the disease. This will result in more people being observed as breaking from the classical presentation and subsets of the disease will become more readily classified in time.
Is collagen found inside cells? How is it created?
no it’s extra cellular only
Created by fibroblasts
collagen is designated genetically how? How is this designation helpful?
COL letter (A,B…) then number for the alpha chain in question.
example COLA4 tells me where the variant is located and thus the problems the patient will likely experience due to a mutation in this area.
Why are you guaranteed to see collagen mutations in your clinical practice? What type of heterogeneity would best describe these mutations and why?
It’s 18kb long with lots of exons so mutations are frequent
loci heterogeneity because there are 35-45 genes that code for it.
Describe the highlights of microfibril assembly from start to finish
collagen composed on Gly-Pro-X (hydroxy proline usually)
Triple helix assembly
Protease cleavage this makes the microfibril and in triplicate makes tropocollagen ( 2 same 1 not)
Tropocollagen is locked in a pentamere
The ends of the cables are staggered/not blunt ended
If the ends are not wrapped you can get problems especially near the C- terminus. N terminus not as bad
These occur mostly by de novo b/c people with massive collagen disease don’t copulate.
What are the 4 most common connective tissue diseases?
Ehlers-Danlos syndrome-joint flexibility problems (stretchy skin)
Epidermolysis Bullosa- skin blisters and tearing (scary blistering like they’re burnt) EB symplex most common
Marfan syndrome- tall long (elastin disease NOT collagen)
Osteogenesis imperfecta- brittle bones
Before you decide the answer is expressivity or penetrance what should you determine?
Whether its alleleic or loci heterogeneity
