What Happens When Things Go Wrong? Flashcards
If there was a change in an amino acid from an arginine to a stop codon at position 1947 how would you write that according to HGVS notation?
p.Arg1947X
What programme might you use to work out whether a mutation might be tolerated or not?
SIFT
What software might you use to work out if a mutation is likely to have an effect on a splice site?
Berkeley Drosophila Genome Project splice site programme.
What software might you use to analyse whether a mutation has any effect on exotic slicing enhancer (ESE) sequences?
ESE Finder.
What databases might you use to retrieve gene data?
Ensembl, universal genome browser.
What does c.5839C>T mean?
A change in the coding DNA sequence of a cytosine to thymidine at position 5839.
What are the causes of trisomy?
Trisomy occurs due to mistakes in meiosis (either in the first or the second division), and is often due to chromosome non-disjunction.
If the mistake happened in the first division it means that the two paired chromosome 21s had failed to separate during anaphase I (will result in trisomy in 2 out of 4 outcomes).
If the mistake occurred in the second division it means that the two sister chromatids of that one copy of 21 failed to separate during anaphase II (trisomy in 1 out of 4 outcomes).
Are trisomies always maternally derived?
Although the majority of trisomies are maternally derived, in principle the non-disjunction could have occurred in either parent. This is likely to reflect the long duration of the first meiotic division in females (from birth to when this particular egg is ovulated). This is different in men, which goes on continuously in the testes from puberty to old age.
What advice would you give a couple who have had a Down syndrome pregnancy with regards their chance of another pregnancy being affected with Down syndrome?
Individual risk of trisomy increases with advanced maternal age (1 in 1500 at 20 compared to 1 in 100 at 40).
However, screening programmes are also in place which could help identify affected pregnancies. Counselling and farther help would be required to help them think about how they would deal with a positive screening result.
If a Robertsonian translocation is responsible for the trisomy then it has implications on further pregnancies. Robertsonian translocations involve an exchange of chromosomal material between two acrocentric chromosomes, just above the centromere. Chromosome 21 is one of the acrocentric chromosomes so can participate in this kind of abnormality. As well as producing a normal and balanced gamete, an individual who carries such a translocation would be at risk of producing a foetus with either complete trisomy or complete monosomy for one of the chromosomes involved. These translocations are responsible for around 3-4% of Down syndrome cases and are phenotypically indistinguishable from other Down syndrome cases. The risk of reoccurrence is higher in these cases, so it is important to know the mechanism of Down syndrome in an existing individual to ensure the best possible risk counselling.
What will the ensembl accession number for the reference sequence for genomic DNA start with?
NG_
What will the ensembl ref sequence for mRNA start with?
NM_
What will the ensembl ref sequence for protein start with?
NP_
