Summary of all lectures including important parts from the workgroups, interactive lectures and computer practicals. NOT ONLY JUST THE SLIDES! Made this summary and used this to study and got a 7.6 on the exam.
Lecture 2 Gemome architecture
Question 1: There are multiple regions in which the causative gene might reside. In one of the regions,
on chromosome 18, a deletion of MIR122HG has been found. Argue based on Fig.1 what type of gene
this is, and how it is processed (2p)
Background to answer question:
There is DNA in the nucleus and DNA in the mitochondria.
The nucleus contains 22 pair of autosomes, 2 sex chromosomes and 20.000 coding genes and 25.000
non-coding genes. Humans have 23 chromosomes.
Why is it difficult to sequence the first axon of DNA? These contain a lot of GC’s because it is a binding
site for ribosomes (lot of hydrogen bonds) and is therefore difficult to split.
There are a lot of components of the human genome. Half of the genome is functional and the other
half is “junk’.
In functional part is:
- Protein coding genes
- Non-coding genes
- Regulatory elements
Protein coding genes
This is what a gene looks like:
For diagnostics we look at the coding sequence. coding part is the dark red. called the coding
genes and are transcriped and translated
,One gene has different isoforms (difference in location? Liver or brain etc.)
Non coding genes: Some genes are not transcribed or translated. miRNA: hairpins Hairpins are
formed and stored outside nucleus. RISC binds to it bind to coding RNA’s inhibition of
translation initiation, inhibition of translation elongation or demethylation of mRNA. and SiRNA:
double stranded RNA or hairpins.
E.g. structural DNA: is not transcribed but only have structural roles. Functional RNA: have functional
roles within the cell and the DNA is transcribed to RNA but this RNA is not translated into proteins.
Introns: is transcribed but the RNA is removed before translation happens by splicing.
Non – coding means: DNA does not get translated into mRNA does not code for proteins.
Feingold syndrome 2: miR-17-92 deletion.
Long non-coding RNA’s: >200 bp. can be anywhere in the genome. They can form hairpins, do protein
binding, DNA binding or RNA binding (preventing function) or bind mRNA. Mostly preventing the
function of RNA, DNA or proteins.
Multiple functions:
1. Scaffold: RNA connects multiple proteins together
2. Decoy: takes away the protein from DNA that it would otherwise bind to. It binds to the
protein so it cannot bind to the dna anymore.
, 3. Guide: the guide RNA brings the protein to the dna by binding to the dna. (transporter)
4. Enhancer: combination between guide and scaffold
5. Active sponges: keep proteins and other RNA’s away from the dna
Natural antistrand transcript (NAT): Can be regulatory the opposite strand of the regulating gene.
If one allele is expressed the other one is not.
Regulatory elements
There is also a promotor downstream of the gene (LNr in picture) so you have two possibilities for
dna to be transcribed from.
Junk is 45% of the human genome, of which less than 0,05% is active. Most abundant: ALU elements
(10% of the huma genome).
Most extreme example of the effect of epigenetic modification on gene expression: x-inactivation.
see x-inactivation computer practical.
DNA methylation causes this inactivation methyl is added.
You have imprinted regions when you are born one allele from mother and one allele from father
one is inactivated and the other one is imprinted. This is essential for normal development.
Deregulation of this results om complex genetic diseases.
If the allele from the mother is deleted on the same place as the fathers inactivated allele there is a
disease if this is the other way around it can cause a different disease. This is because in the one it
misses the maternal information and on the other one the parental information different
syndrome even though it is the same deletion / region.
, (See translational genomics diseases.)
Sometimes it happens that you get two chromosomes from the mother or 2 from the father
uniparental disomy.
Answer to question: if the lines are thick: coding gene for proteins. The lines are not thick so does not
code for a protein. It’s a RNA coding gene. HG stands for host gene.
MiRNA are always hairpins.
CSPP1 lies next to COPS5 (Fig. 1) and the two genes overlap. Describe two mechanisms by which the
two genes might interfere on transcript level (2p)
Answer:
1)They might hamper each other’s transcription by a clash of polymerases (1p). 2) They might
influence gene expression by nuclear retention or chromatin modification (1p).
SSA notes interactive lecture genome architecture
Pseudogenes: genes without a function in the cell.
Golden path length: skips the redundant regions of our genome little bit smaller than the total base
pair length.
Long non-coding RNA (lncRNA) can have different functions. They can, for example, act as a scaffold
bringing together different proteins in a complex. Which other three separate functions are lncRNAs
assumed to have according to Rinn and Chang1?
1. Scaffold: RNA connects multiple proteins together
2. Decoy: takes away the protein from DNA that it would otherwise bind to. It binds to the
protein so it cannot bind to the dna anymore.
3. Guide: the guide RNA brings the protein to the dna by binding to the dna. (transporter)
4. Enhancer: combination between guide and scaffold
5. Active sponges: keep proteins and other RNA’s away from the dna.
,In the UCSC browser coding genes are indicated as a thicker line compared to non-coding genes.
UTRs are shown as open boxes on ENSEMBL the UTR on the 5’ end is always shorter than the UTR
on the 3’ end. The way it is transcriped is indicated with arrows.
Not all alternative transcripts are necessarily biologically relevant: the non-protein coding ones and
The ones without a coding sequence CCDS are not relevant. Only the ones with a ncbi refseq match
are relevant.
red is deletion, blue id duplication. these deletions and duplications are produced by
recombinations/crossing over. Could result in non allelic non homologous recombination they miss
align during duplication.
High peaks in the UCSC browser can indicate conservation.
centromeres are very difficult to sequence as it is very repetitive/ has many repeats.
Lecture 3 genome variation and chromosomal
abnormalities
Genome variation is every different compared to the reference gene. The reference gene is the
baseline (however this is still one reference and is not always reliable can be from only one
individual).
Variation: any deviation from reference genome.
Polymorphism: very common variation > 1% of the alleles in the population
Mutation: variation < 1% of alleles in a population.
Pathogenic: causing disease because of this mutation or polymorphism. If there is no disease we call
it benign.
There are different kind of genome variations. Single nucleotide variant (SNV), insertion or deletion
(indel), repeat expansion (repeat of 2 to 6000 base pairs) ,copy number variant (CNV) deletion or
, duplication larger than 1000 bp., structural chromosomal abnormalities (upside down) and lastly
aneuploidy: one chromosome extra or less.
The main groups and types of mutation and effect on protein product:
Synonymous: substitution results in no different amino acid. stays the same . Non-synonymous:
animo acid changes missense. When they change into a stop codon: nonsense.
On DNA level you thus have substitution, deletion and insertion as the main mutation types.
Silent changes:
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