molecular genetics and pathology Flashcards
What is the major difference between DNA and RNA
DNA- deoxyribose
RNA- ribose
RNA also has an additional OH.
what significance does the extra OH in RNA have and why does it make the molecule unstable.
RNA can result in nucleophillic attack of the phosphodiesterase bond, which causes it to hydrolyse and split.
In what direction is the DNA synthesised
5 to 3 direction.
Is the sense strand the strand that gets copied or the other strand.
sense strand ends up in the mRNA
explain the process of DNA replication.
2 strands of DNA unravel
Each strand forms a template strand to which complementary nucleotides attach
This forms 2 new identical DNA strands.
How many Mbp is the human genome made up os
3000
what percentage of the human genome is non coding DNA
> 90%
how many protein coding genes are there
20,000
define single copy sequence
(non-repetitive)- sequence is not repeated anywhere else on another chromosome, .
Are most genes single copy sequences
Yes
2 types of repetitive sequences
Interspersed repeats- spread through the chromosome- Alu
Satellite- DNA large blocks of repeated DNA
define transcription
copying RNA
define translation
turning RNA into a protein
define gene
functional unit of DNA
main components of genes include.
exons, introns and regulatory sequences (promoter, enhancer, locus control regions)
where are problems arise in genes
in which processes
transcription cleavage and polyadenylation Splicing Translation Post translational modifications
where does transcription, cleavage and polyadenylation and splicing take place
Nucleus of the cell
where do translation and post translational modifications take place
cytoplasm
what is exon skipping
missing out exons when encoding protein sequences
why do we use exon skipping
helps create diversity and increase the number of potential sequences for proteins.
what is the first stage in gene evolution
duplication and divergence
what is a gene family
structurally related genes
what causes a duplication to take place in the ancestral gene.
Inaccuracy in the replication or crossing over of 2 genes next to each other.
what causes divergence (splitting of genes from there family/ origin)
mutations in these duplication genes
what is the name of a gene which becomes functionally inactive due to duplications and mutations in a previously active gene
Pseudogenes.
what are pseudogenes processed genes
intronless copies of other genes.
are processed genes function
mostly no.
How are processed genes formed
ancestral gene forms mRNA which then via reverse transcription reintegrates into a processed gene.
when a mutation occurs in a processed gene what is is called
a processed pseudogene
which part of the chromosome are satellite DNA sequences found
centromeres and heterochromtic (lots of chromatin) chromosomal areas
what time of repeats are in satellite DNA sequences
Simple tandemly repeats
what are the main factors which are always present in satellite DNA sequences.
centromere repeat
chromosome specific.
Is the repeat sequence sequence different maternally and paternally
Yes
example of a satellite DNA which is found at the centromeme
alphoid
how many bp repeat sequence is the alphoid
171
does the alphoid sequence have chromosome specific variations
Yes
why is alphoid DNA important in chromosome formation
is is required to assemble the centromere.
where are interspersed DNA repeat sequences located
throughout genome
between and within genes.
what is a example of a interspersed DNA repeat sequence.
Alu repeat.
how many bp is Alu
300
how many copies of Alu are these
500,000
how are interspersed DNA sequences dispersed
retrotransposition.
what is the name of the sequences which enable the maternal and paternal chromosomes to line up for meiosis 1
recongnition sequences.
which chromosome has a lot of Alu repeats
chromosome 1
what problems can result in lining up of chromosomes 1- due to excessive Alu repeats
the wrong sections can line up together
what is the consequence of wrong sequences lining up in meiosis due to alu repeats.
imbalanced amount of exons with one strand being duplicated and the other having deletions.
what are the different types of mutations
large deletion and insertions-
Duchennes muscular dystrophy
Charcot- marie tooth disease.
Gross rearrangements-
haemophilia A
Point mutations
Trinucelotide repeat expansions.
F8 gene in on chromosome X has a repeat sequence on chromosome 1 but they are in the opposite direction what occurs in chromosome X in order for haemophilia to occur
Intrachromosomal recombination occurs.
This results in inversion as all the exons are till present but in a different orientation-
define point mutation
single nucleotide changed
define missense mutation
change in nucleotide could mean a different amino acid. this could be conservative where the amino acid is swapped for a similar amino acid
define silent mutation
change in nucleotide but same amino acid is coded for.
Why are CpG sites more prone to mutations.
they are the site of methylation.
Methylated cytosine is similar to which base (and can therefore be substituted for it)
thymine
define nonsense mutation
Truncated protein produced
define frame shift
- Deletion of a base results in a change in the frame of which the codons are read after the deletion.
- Alters protein sequence beyond mutation
- May truncate protein- if stop codon results.
define change in splice junction mutation.
- Change in the bases of a splice junction from GT (common splice site) to AT will result in the splice junction not being recognised.
- Therefore the DNA sequence be spliced form the next GT and this will result in some intron being part of the mRNA and hence protein.
what are the references used in mutation nomenclature
– Genomic DNA (g.)
– cDNA (c.)
– Protein (p.)
how is the base number at which the mutation takes place numbered.
Splice junction mutation- number of the base before the splice junction (122), +1 because it is the next base,
C. = cDNA., 5C>T means the fifth base is changed from C to T. P = protein, Val2 Ala means that alanine, the second amino acid, has been changed to valine.
what type of inheritance are loss of function mutations typically
recessive
what is the mutation which is commonly found in achondroplasia
FGFR3 G380R (glycine to arginine)
when do you have dominant achondroplasia
often result as the protein, which is formed from the mutation, has a gain in function.
when do you get recessive achondroplasia
often result as the protein, which is formed, has a loss of function.
define trinucelotide repeat expansions
3 nucleotides alternatively repeated.
what common disorders is the polyglutamine repeat (CAG) commonly found in
– Huntington’s disease
– Spinocerebellar ataxias
conditions which are caused by large non-coding repeat expansions
– Fragile X syndrome – transcriptional silencing – Myotonic dystrophy – Mutational instability – Occasional (eg Huntington’s) – Frequent (eg fragile X)
define polymorphism
where the number of repeats of a sequence is within the normal range
what trinucleotide repeat cues fragile X syndorme
CGG repeat expansion
how do you get from a permutation to a mutation to form a large non-coding repeat expansions to cause a disease
over generations of passing on the permutations and if enough permutations occur then a mutation will occur.
Fragile X I heritance pattern is caused by anticipation. define anticipation
Over generations the number of CGG repeats increase
what does the CCG mutation inffragile x syndrome cause
altered chromatin structure resulting in the shutdown of transcription of the gene.
