DNA rearrangement hotspots in the genome transforming mice ... · Sequence similarity • Homology:...
Transcript of DNA rearrangement hotspots in the genome transforming mice ... · Sequence similarity • Homology:...
DNA rearrangement hotspots in the genome
— transforming mice into man
Bioinformatics course (MTAT.03.239) 17.11.16 Priit Adler
Evolution of species or sequences
• All living organisms are related to each other through evolution.
• Any pair of organism have common ancestor some time in the past, from which they evolved.
• Mutations and selection over long periods of time can result in considerable difference between present-day sequences derived from the same ancestral sequences.
• The base pair composition of the sequences can change due to point mutations (substitutions) and the sequence lengths can vary due to indels (insertions/deletions).
From last time
Sequence similarity• Homology: derived from a common ancestor-gene.
• Orthology: homologous genes in different organisms.
• Paralogy: homologous genes in one organism that derive from gene duplication.
• Gene duplication: a gene is duplicated in multiple copies that can each evolve in separate directions and assume new functions.
From last time
Adding genome rearrangements
• Involves genomic DNA deletion, duplication, inversion and translocations
https://public.ornl.gov/site/gallery/originals/Mouse_and_Human_Genetic_Similarities_-_original.jpg
• ~245 rearrangements
• ~300 large syntethy • blocks
https://twitter.com/torstenseemann/status/524675360697229312
http://www.nature.com/nature/journal/v428/n6982/full/nature02426.html
Human vs Mouse vs Rat X chr
Human vs Mouse vs Rat X chr
http://bioinformaticsalgorithms.com/
Rearrangements and cancer
DNA (chromosomes/genes do happen to break)
Sometimes the repair is not perfect
It can lead to various types of cancer
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3065307/
http://bioinformaticsalgorithms.com/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2652200/http://bioinformaticsalgorithms.com/
Rearrangements in Breast Cancer model Cell
Line MCF7
How to get from genome Q to genome P
Random Breakage Model
Sort by Reversals
Greedy approach
+1 -7 +6 -10 +9 -8 +2 -11 -3 +5 +4
Breakpoint theorem
+3 +4 +5 -12 -8 -7 -6 +1 +2 +10 +9 -11 +13 +14
2 Break distanceFrom linear chromosome to circular
http://bioinformaticsalgorithms.com/
2-break distance d(P,Q): Minimum number of 2-breaks
transforming genome P into genome Q
Breakpoint Graph
http://bioinformaticsalgorithms.com/
2-break distance between genomes P and Q:
d(P,Q) = blocks(P,Q) - cycle(P,Q)
Fragile Regions in the Human Genome
If Random Breakage Model (RBM) is correct, 2 break distance between Human and Mouse should
be 280/2 = 140
From 2-Break distance theorem we can calculate that 2 break distance between Human and Mouse:
280 synteny blocks 35 cycles in breakpoint graph
280 - 35 = 245
245 != 140
New “better” models
RBM - Random Breakage Model
FBM - Fragile Breakage Model
TFBM - Turnover Fragile Breakage Model
Chapter 6 videos
https://www.youtube.com/playlist?list=PLQ-85lQlPqFOcGz6A3g2ZArRL09Ffpp_N
Bioinformatics Algorithms
An Active Learning Approach
1st Edition:
www.ester.ee/record=b4422219
2nd Edition:
www.ester.ee/record=b4517979
https://youtu.be/yfXeKPt0nw4
http://bioinformaticsalgorithms.com/index.htm
Chapter 5 homeworkhttp://rosalind.info/classes/337/
Due 30.11.16 midnight
tasks 63-73: choose min 4, max 6 tasks