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 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
what are the treatments of cystic fibrosis?
Intensive physiotherapy to clear mucus from lungs and tablets containing enzymes to aid digestion (creon)
what is the patterns of inheritance of cystic fibrosis?
- Autosomal recessive disorder that affects 1 in 2500 babies
- Recessive allele
- Homozygous recessives show the disease
- Heterozygotes are carriers
what is Huntington’s disease?
- A neurological disorder
- Results in involuntary muscle movement (chorea) and progressive mental deterioration
- Age of onset is variable but mostly in middle age
what is the cause of Huntington’s disease?
- Gene (huntingtin) lies near the short end of chromosome 4
- Inherited as a dominant mutated allele
what cause the mutation of Huntington’s?
- Mutation is an unstable segment of a gene coding for a protein a gene ‘stutter’
- A stutter is an abnormal number of base triplets in this case CAG (37 – 100)
what is a stutter?
- A stutter is an abnormal number of base triplets
How is Huntington’s disease inherited?
- The mutation is inherited as a dominant allele.
- Most sufferers are heterozygous and have a 1:2 chance of passing on the condition
what are the symptoms of Huntington’s disease?
- progressive mental deterioration;
- brain cells lost;
- involuntary muscle movements (chorea)
when can pedigree analysis be used?
If the condition is caused by an allele of a gene showing a simple inheritance pattern (e.g.cystic fibrosis) then pedigree analysis can be used
what is a pedigree?
A pedigree is a family tree (a kindred) of a group of related people
what does autosomal dominant mean?
Both sexes affected
Visible in all generations
Only 1 parent needs to carry the allele to be inherited
what does autosomal recessive mean?
Both sexes equally affected
Not visible in every generation, only visible in a few generations
Both parents need an allele to be passed onto child to be inherited
what is an X linked recessive?
More common in males
Not in every generation
Parents not showing disease but children do
Mother must be carrier for disease
what is genetic screening?
Pedigree analysis only determines probability of an individual being a carrier or showing the disorder
Certainty comes from some form of test
what are the 2 applications of genetic screening?
- Genetic screening of carriers
- Genetic screening of the embryo/foetus
how would you screen carriers?
Need to know gene specific sequence before disease can be tested for.
Using a DNA probe
Identifies one mutant allele e.g. CF allele
Probes only available for a small number of genetic disorders.
why are probes only available for a small number of genetic disorders?
because disease must be caused by:
Single allele
Single mutation that causes disease
how would you screen the embryo?
After IVF a cell can be removed at 8 cell stage and DNA tested
ways to genetically screen an embryo:
- amniocentesis
- chronic villus sampling
what is amniocentesis?
using an ultrasound, a long needle which is used to withdraw amniotic fluid containing foetal cells.
what is chronic villus sampling?
a fine catheter is inserted via the vagina and cervix. A suction tube which is used to remove cells from the chorion, where the placenta will develop
once foetal cells are extracted, what happens?
Fetal cells are extracted and karyotyped or their DNA extracted and analysed
advantages of genetic screening?
- Can identify presence of disorder
- Removes uncertainty
- Allows early treatment which may improve life expectancy
- Allows informed choices about having a family
- Allows choice re termination
- Allows choice re adoption
what are the disadvantages of genetic screening?
- False positives/negatives
- May not be test for all mutations
- Not available for all conditions
- Presence may not result in condition
- Confirmed presence gives stress /fear
- Discrimination re employers
- Ethics of termination
what is genetic counselling?
If a couple have been identified as being at risk of having a child with a genetic disorder a counsellor provides advice before or after screening
what is the role of a genetic counsellor?
- genetic counsellor, provides information / explains options ;
- confidentially ;
- in light of, beliefs / culture ;
- about risks of screening ;
- about quality of life with condition ;
- about life expectancy ;
- about treatment of condition ;
- about termination ;
- about use of, donor / IVF with screening, on another occasion ;
- about chance of it occurring in future pregnancies using pedigree diagram
when is the amniocentesis usually performed?
between 13 - 16 weeks of pregnancy.
what are the risks of an amniocentesis?
there is a slight risk of spontaneous abortion as a result of the test procedure
when can the chorionic villus sample be collected?
in 9 - 12 weeks of pregnancy
comparison between results of amniocentesis vs chorionic villus sampling?
amniocentesis: results available 2-3 weeks later
chorionic villus sampling: quicker results, because the cells taken are actively dividing
