genetics Flashcards
What is meant by the term “compound heterozygote”?
At the same gene, each allele has a different mutation that interferes with normal protein function. This causes an autosomal recessive pattern with expressed phenotype.
Why would the parents be clinically unaffected by these mutations?
Each parent has only one mutated allele, so the wild-type allele can make enough functional protein that no pathology is expressed.
What is the chance that siblings to this child will have a nonsense mutation or frameshift deletion, but not both
There is a 50% chance siblings to this child would only have one mutated allele but not both, resulting in enough functional protein that no pathology is expressed but they will be carriers for the inherited mutation.
WHAT IS THE DIFFERENCE BETWEEN autosomal recessive, dominant, x linked and chromosomal disorders?
What if the child was to inherit both mutations?
25% chance of this happening.
The couple is 13 weeks pregnant with a second child. What are their options for prenatal testing?
non invasive prenatal testing
The clinical geneticist draws up a pedigree. What features would you expect to see in the pedigree for this autosomal recessive condition?
Typically affects both males and females equally, “skipping generations” may be visible where affected children (homozygous for the affected gene) usually have unaffected carrier parents. V
What ethical issues could arise from genetic analysis of the child?
Is it actually helpful to know if the child has a disease or not. Do the parents actually want this and what if there isn’t a cure.
Have we gained consent from the child to do this? Is it clinically appropriate to do this at this age, until the proband consents?
This is less of an issue but understanding the mechanism behind a child’s disabilities can be therapeutic for parents as they navigate caring for an affected child.
Explain how next generation sequencing works
NGS allows for massively parallel sequencing of DNA, meaning simultaneous analysis of DNA sequences in a single reaction.
NGS process;
Cutting up genomic DNA into small pieces and adding linkers (small pieces of known DNA sequences) to each end.
Putting DNA onto a glass slide and
using PCR to amplify the fragments
During amplification each nucleotide (A, C, G and T) gives a different colour of light, which is recorded.
Compared to Sanger sequencing;
Higher throughput
NGS generates shorter reads of sequencing (50-400 base pairs) vs Sanger sequencing (500-1000 base pairs)
Takes a lot longer to use sanger sequencing
describe nonsense mtuation, frameshift deletion, and recessive
Single base change that changes a codon coding for an amino acid to a stop codon
Deletion of a number of bases in the genomic sequence that is not in a multiple of 3. ie. the reading frame for transcription is shifted
Requires mutations in both genes to produce the phenotype
The couple is hoping to become pregnant again. What are the possible consequences for younger siblings?
25% chance of getting both wild type alleles (normal phenotype), 50% chance of getting just one of either mutated traits, 25% chance of getting both mutations and expressing the phenotype (Bit unsure of this answer, if someone could check it and confirm or correct!)
What ethical issues may arise from prenatal screening?
Prenatal testing may not always be accurate because we are only testing (limited) for common chromosome disorders and this doesn’t guarantee absence of other abnormalities/congenital developmental disorders
Potential risk of lab testing error > influence parents decisions?
May lead to an abortion. Patients and doctors view of if this is right/wrong, doctor must provide options to patient even if he/she disagrees with it
Potentially mismatched paternity arising
Discuss how identifying the genetic changes responsible for the child’s clinical features could be beneficial to the child and their family
Identifying the genetic changes could help guide research for the treatment of this syndrome. Identifying the genetic changes could also inform what other aspects of the body could be affected by this genetic change, which could improve the care of the child in the future.
If gene therapy was a possibility for this disease in the future, outline the possible approaches that may be used.
Electroporation, lipofection, microinjection, integration into the genome via viral ‘vehicles’. Can either be in vivo or ex vivo.
What screening tests might be available to this couple, and what relevant risk do they carry?
Ultrasound early in pregnancy (8 weeks), detailed scan can be done at 18 weeks to check for cardiac abnormalities. The main test however would be maternal serum test at trimester 1 which can be paired with nuchal translucency to screen risk for down-syndrome. These tests are generally non-invasive and carry very little risk. However if the screening tests show that the baby is at risk of having down-syndrome, they must access diagnostic tests in order to receive a clear clinical diagnosis, which does carry some risk of miscarriage and are more invasive.
Non-invasive prenatal testing is available via private funding, this is a blood test that captures foetal DNA to be tested. Not routinely offered in NZ.
Nuchal translucency ultrasound (10-13 weeks) and maternal serum testing (15-17 weeks).
