Human Genetics - Genetic disorders Flashcards
what is the definition of a genetic disorder?
an inherited malfunction. A disorder that is caused by a genotype that gives rise to a poorly adapted phenotype in an environment in which other genotypes give rise to healthy phenotypes
what may cause a genetic disorder?
- gene mutations (on sex chromosome or autosomal chromosome)
- changes in chromosome structure
- changes in number of chromosome
what can cause Down syndrome?
can be caused by change in either chromosome number or chromosome structure
how often does Down syndrome occur?
1 in 700 births
risk factor for Down syndrome?
frequency increases with age of mother
what are the characteristics of Down’s syndrome?
- Folds on eyelids (epicanthal folds)
- Slightly flattened face
- Heart problems common
- Poor muscle tone
- Short in stature
- Various degrees of learning disability
what is the chromosome cause of Down’s syndrome?
have an extra copy of genes normally found on the long arm of the chromosome 21.
This is caused by:
- trisomy 21
- translocation
what cause trisomy 21?
caused by error in nuclear division
- results in a person having an extra copy of chromosome 21
- commonly when chromosomes fail to separate in meiosis I
- one daughter cell has both members of a chromosome pair
what is nondisjunction?
Commonly when chromosomes fail to separate in meiosis I
nondisjunction and trisomy disorders
When this cell is fertilised by a haploid gamete the zygote will have 3 copies of chromosome 21 instead of 2
how many cases are caused by trisomy 21?
95%
Most arise by chance so is NOT inherited
in 75% of cases with Down syndrome…
the extra chromosome comes from the mother
women over 35 and down’s syndrome
have an increased chance of having a child with Down’s syndrome but
why are over 35’s more at risk…
Oocytes held in prophase 1 of meiosis from before birth to just before ovulation therefore the cell is vulnerable to external and internal factors during this time resulting in increased chance of nondisjunction as mother ages
what is translocation?
Translocation is when one part of a chromosome breaks off and joins to another. The long arm of chromosome 21 may break off and join to another autosome (usually 13,14 or 15)
what cause translocation in Down’s syndrome?
After meiosis a gamete may have chromosome 21 AND a chromosome with an additional portion of chromosome 21 and so when it is fertilised it will effectively be trisomic
offspring from mating between translation carrier and normal individuals
- 1/3 of surviving offspring expected to be Down
- another 1/3 surviving progeny expected to be carrier (this form can be inherited)
what is cystic fibrosis caused by?
Caused by a mutation of a a gene called CFTR (cystic fibrosis transmembrane regulatory protein) found on the long arm of chromosome 7
what happens in someone without CF with the normal allele?
- The normal allele codes for the CFTR protein that forms chloride ion channels in the plasma membrane of the cells lining the airway, lung and gut and other organs.
- Allows Cl- out and causes H20 to leave to keep surfaces moist
what happens if someone has the mutated CFTR gene?
- Chloride ions do not move across the epithelial cells
- Sodium ions do not follow as they normally do
- Water should follow and make mucus thin and runny, but this does not happen so the mucus is thick and sticky
how many mutations are there?
> 400 types of mutation
what is the most common mutation and the result?
The commonest mutation (δF508) results in the deletion of three bases.
what causes the Cystic Fibrosis mutation?
One amino acid (phenylalanine) is missing in the polypeptide chain.
This causes an abnormal CFTR protein which is not placed into the plasma membrane so chloride ions are not moved out of the cells.
what are the symptoms of cystic fibrosis?
- Thick, dehydrated mucus builds up in lungs
- Increased bacterial infections
- Recurrent infections scar lung tissue = leads to lung failure
- Narrowed airways/reduced O2 uptake = fatigue
- Thick, dehydrated mucus blocks secretion of digestive enzymes from pancreas into duodenum
