CB13: Gene mutations & inherited disease Flashcards
Which mutations lead to small changes in DNA?
- Point mutations
- Deletions
- Insertions
How do point mutations, deletions & insertions lead to animal disease?
They lead to a change in DNA sequence so the amino acid sequence/gene expression is different.
Which mutations lead to big changes in DNA?
Chromosomal rearrangements like deletions, duplications, translocations, polyploidies & aneuploidies.
How do chromosomal rearrangements lead to animal disease?
They lead to a massive change in the genome & thus the DNA, usually disease is very severe.
What are point mutations?
Mutations that affect a single base.
What are the two types of point mutations and what are their differences?
Transition: switch purine for purine or pyrimidine for pyrimidine.
Transversion: switch purine for pyrimidine & opposite too.
What are the 5 main types of inherited diseases?
- Autosomal dominant
- Autosomal recessive
- X-linked recessive
- Sex-limited inheritance
- Polygenic diseases
What are the characteristics of autosomal dominant disease?
- Affects male & females equally
- Does NOT skip generations
- Affects homozygous dominant & heterozygous individuals
- Affected individuals have at least 1 affected parent
- Easy to eradicate as individuals are easily identified
- Rare if lethal before reproductive age
- Common affected ancestor to all affected individuals
What are some examples of autosomal dominant disease?
Lack of tail in Manx cat (lethal if homozygous dominant)
Comb form in roosters (controlled by 2 genes)
What are the characteristics of autosomal recessive disease?
- Affects males & females equally
- May skip generations
- Inbreeding increases frequency
- Can appear suddenly in a breeding line
- Difficult to eradicate as carriers go unnoticed
What are some examples of autosomal recessive disease?
Double muscling in cattle (exceptional muscularity due to mutation on myostatin gene (negative muscle regulator) on chromosome 2)
Malignant hypothermia in pigs
What is the genetic mutation that leads to double muscling in Piedmontese cattle?
G to A substitution leads to Cys to Tyr substitution. This causes a destabilisation of 3D structure.
What is the genetic mutation that leads to double muscling in Belgian Blue cattle?
11 nucleotides are deleted so the protein is truncated.
What are positive effects of double muscling?
- Less bone & fat
- Tender meat
- Lower collagen
- Increased feed efficiency
What are negative effects of double muscling?
- Decreased fertility
- Greater risk of lameness due to weaker limb bones
- Poor welfare
- Obstructed labour (dystocia)
- Underdeveloped external genitalia
What is malignant hypothermia in pigs?
When exposed to mild stress, pigs develop increased temperature, acidosis & muscle rigidity leading to rapid death.
What are the consequences of malignant hypothermia on pig meat?
It’s not as desirable, it’s paler.
What mutation causes malignant hypothermia in pigs?
A missense mutation –> different amino acid in calcium release channel
What is the test to detect pig malignant hypothermia?
Expose pigs to halothane. Positive if hindquarters stiffen within 2 minutes.
Why does malignant hypothermia not affect all offsprings of affected parents?
Due to a partial environmental effect.
What are the characteristics of X-linked recessive disease ?
- Mostly affects males
All males with mutated X allele are affected (hemizygous condition) - Females may be affected or carriers
- Affected males NEVER transmit the disease to male offsprings
- Affected females appear with inbreeding
What are examples of X-linked recessive disease ?
Some types of haemophilia
Which types of haemophilia are X-linked recessive?
Types A & B
What are the characteristics of sex-limited inheritance?
- Affects autosome (a specific sex tissue/organ)
- Only seen in 1 sex but transmitted to both sexes
What is an example of sex-limited inheritance?
Cryptorchidism in dogs: where 1/both testicles don’t descend
Both females & males carry the affected allele
What are the characteristics of polygenic disease?
- Caused by many genes & environment
- Seen in groups that share genes & environment
- Does not follow Mendelian inheritance
- Follows continuous distribution –> sometimes only seen after a threshold
- Can be sex-linked
- Difficult to eradicate
- True genetic effects difficult to identify
What are examples of polygenic diseases ?
Cardiac disease, cancer, hip dysplasia
When is a condition likely to be genetic ?
When there is increased incidence in some breeding lines/breeds & the removal of environmental factors leads to little to no change in the incidence of the disease.
