English summary of Translational Genomics containing many pictures
11 views 0 purchase
Course
Translational Genomics (NWIBM0722023KW1V)
Institution
Radboud Universiteit Nijmegen (RU)
This document is written in english. It contains summaries of all lectures given in the course Translational Genomics. It also includes many pictures for better understanding. The lectures are about genome architecture, determination of variations/mutations, mandelanian inheritance, microsatellite ...
Inhoudsopgave
Week 1...................................................................................................................................................3
LE Introduction...................................................................................................................................3
LE Genome Architecture.....................................................................................................................3
The human genome........................................................................................................................3
Functional DNA:..............................................................................................................................3
‘Junk’ DNA......................................................................................................................................5
The epigenome...............................................................................................................................5
LE Genome Variation & Chromosomal Abnormalities........................................................................6
Genome variations.........................................................................................................................6
Chromosomal abnormalities..........................................................................................................9
Week 2.................................................................................................................................................14
LE Determination of variation...........................................................................................................14
Genome-wide determination of variation....................................................................................14
Local determination of variation..................................................................................................15
LE Mendelian inheritance & SNVs....................................................................................................16
Inheritance patterns.....................................................................................................................16
Coding variants: protein level.......................................................................................................17
Coding variants: nonsense mediated mRNA decay (NMD)...........................................................18
Mitochondrial inheritance............................................................................................................19
Week 3.................................................................................................................................................21
LE Microsatellite instability: diagnostics & mechanisms...................................................................21
Molecular mechanisms of microsatellite instability.....................................................................25
LE Microsatellite instability: disease mechanisms............................................................................29
Missplicing, nuclear foci and RAN translation...............................................................................30
Week 4.................................................................................................................................................32
LE Microsatellite instability: Molecular therapy...............................................................................32
Exam Preparation: microsatellite instability Q&A.............................................................................34
LE The needle in the haystack: Mendelian inheritance....................................................................35
Exome and genome sequences....................................................................................................35
Analysis of exome and genome sequences..................................................................................37
Week 5.................................................................................................................................................38
LE Multifactorial traits......................................................................................................................38
Week 6.................................................................................................................................................38
LE Non-invasive prenatal DNA & pre-implantation diagnostics........................................................38
, Fetal DNA in maternal blood........................................................................................................39
NIPT..............................................................................................................................................40
Numerical chromosomal abnormalities........................................................................................41
CNVs.............................................................................................................................................42
SNVs..............................................................................................................................................43
Pre-implantation genetic testing (PGT).........................................................................................44
Week 7.................................................................................................................................................46
LE The importance of model organisms in humans..........................................................................46
LE Drosophila as a model to study neurodevelopment/ Crash course in genome editing in retinal
diseases............................................................................................................................................46
LE Genome editing therapies for USH2A..........................................................................................48
LE Prime Editing: a novel CRISPR/Cas0-based...................................................................................48
Q&A......................................................................................................................................................49
,Week 1
LE Introduction
Waiting time for final diagnosis is very long. Many patients need to see multiple doctors before
getting their diagnosis
SSA more important than lectures
Only the red line & nociception are obligatory
The work groups (not bold) is also exam material
Genetic dominant disorders often skip a generation. And the phenotype can develop later on in life.
LE Genome Architecture
The human genome
~20.000 genes and ~25.000 non-coding genes in 22 pair autosomes and 2 sex chromosomes
Multiple deletions in a row =
GC have 3 hydrogen bonds, AT have 2
The first exons are often GC rich which are difficult to translate because the ribosome binds
Functional DNA:
- Protein coding genes
o Intergenic and intronic sequences
o Exon is coding, intron is spliced out
, o
o Genes have different isoforms that get expressed in different environments
- Non-coding genes
o Long non-coding or small non-coding RNAs
o Small non-coding RNAs: long gene is cut into smaller pieces (200 nt)
piRNAs: gene splicing of transposons to make sure transposons don’t jump
(Transposon, class of genetic elements that can “jump” to different locations
within a genome. Although these elements are frequently called “jumping
genes,” they are always maintained in an integrated site in the genome. In
addition, most transposons eventually become inactive and no longer move.)
miRNAs (microRNA) target coding genes. Regulate gene expression by base-
pairing with mRNAs.
Always in hairpin formation. They are transported, RICS complex is
formed and it can
o Inhibit translation
o Inhibit elongation
o Or mRNA deadenylation (shortening of mRNA poly A tail
Deletion of a miRNA gene or part of, can cause diseases
siRNAs (small interfering RNA): about 21 nt, gets into hairpin-RNA or dsRNA
bind to mRNA -> degradation -> interfering with translation. Target
transposons and exogenous genes
o Long non-coding RNAs: RNAs of 200+ nt
The benefits of buying summaries with Stuvia:
Guaranteed quality through customer reviews
Stuvia customers have reviewed more than 700,000 summaries. This how you know that you are buying the best documents.
Quick and easy check-out
You can quickly pay through credit card or Stuvia-credit for the summaries. There is no membership needed.
Focus on what matters
Your fellow students write the study notes themselves, which is why the documents are always reliable and up-to-date. This ensures you quickly get to the core!
Frequently asked questions
What do I get when I buy this document?
You get a PDF, available immediately after your purchase. The purchased document is accessible anytime, anywhere and indefinitely through your profile.
Satisfaction guarantee: how does it work?
Our satisfaction guarantee ensures that you always find a study document that suits you well. You fill out a form, and our customer service team takes care of the rest.
Who am I buying these notes from?
Stuvia is a marketplace, so you are not buying this document from us, but from seller daniquelichtenberg. Stuvia facilitates payment to the seller.
Will I be stuck with a subscription?
No, you only buy these notes for $6.84. You're not tied to anything after your purchase.
