GENETIC TESTING Flashcards
Describe lethal alleles.
one or more genotypes are depleted or missing, because embryos with these genotypes die. This alters the phenotypic ratio from the predicted Mendelian ratio.
Everyone is thought to carry several lethal recessive alleles, which can cause miscarriages.
How can lethal mutations modify mendelian ratios?
Mutant allele (dominant) which is lethal early in life (either MM or Mm) will not survive in the population, as all individuals carrying it will die without breeding. A mutant allele that is lethal when only homozygous can survive in the population and can affect mendelian ratios, as there will be no MMs.
Describe recombination in meiosis.
Genetic material “crosses over” between maternal and maternal chromosomes.
2 main outcomes: greatly increases individual diversity and uniqueness of offspring, and further increases the risk of mutations.
Typically occurs between homologous regions, some of which are more likely to cross over than others.
What are some prenatal genetic screening procedures?
Ultrasonography Cordocentesis Amniocentesis Chorionic villus sampling Fetal cell sorting Preimplantation diagnosis
Describe ultrasonography
Generally done at 17-20 weeks gestation to detect neural tube defects, skeletal dysplasia, and abnormal abdo organs.
Describe Maternal Serum screening.
Done in first trimester, 10-13 weeks. Assay mothers blood for certain proteins specifically associated with pregnancy. Can be combined with nuchal translucency assessment by ultrasound. has sensitivity for DS of 90%.
Describe amniocentesis.
15-18 weeks gestation. Culture cells shed by fetes into amniotic fluid. Prepare karyotype to detect chromosome abnormalities, and can detect neural tube defects. Has 0.5% risk of inducing miscarriage.
Describe chorionic villus sampling.
8-12 weeks gestation. Sample feral tissue from placenta and construct karyotype.
Describe feral cell sorting.
6-8 weeks and later. Use cell sorting ago identify fetal cells in mothers blood. Technique is still being perfected and is not used routinely. Poses no risk to the fetes.
based on the fact that some of the foetuses cells pass into mothers circulation.
describe preimplantation genetic diagnosis.
One cell is removed from the embryo at 8 cell stage for analysis before implantation during IVF. Complete single-cell PCR to amplify DNA from cell to test for genetic abnormalities.
Describe cystic fibrosis.
Abnormal mucous and other body fluids. Damge to lungs, pancreas and other organs. Main clinical symptoms include recurrent bacterial infections of the lungs, pancreatic insufficiency, hepatobillary disease, genital tract abnormalities and abnormal sweat.
What are the treatments for CF?
Physiotherapy to clear fluid, lung transplant.
Nutritional supplements and pancreatic enzymes.
Describe the molecular pathogenesis of CF
Abnormality in “cystic fibrosis transmembrane regulator” which is important in the transport of chloride ions in secretory tissues. Generally affects ATP binding site.
The disease arises from osmotic imbalances in body secretions. defects in ion transport mechanisms in secretory cells lead to not enough water entering secretions –> thickness.
Describe screening for CF.
- First tier screen: all infants at 2-4 days old undergo a blood immunoreactive trypsin test
- second tier screen: if abnormally high serum trypsin, or family history of CF, or symptoms of CF are present, person is screened for major CFTR gene mutations.
Further investigations include a sweat test at 3-4 weeks of age, genetic counselling for parents and clinical assessment for children with symptoms, or 2 mutated alleles.
What are the 2 indications for prenatal CF testing? When can it be performed?
Indications for prenatal testing are 1. an index case in the family, and 2. both parents are known carriers.
Can be performed around 11 weeks (chorionic villus sampling) or around 16 weeks by amniocentesis.
