ECON 546 Lecture Notes - Lecture 6: Heat Map, Fusion Gene, Summary Statistics
27 Jun 2018
School
Department
Course
Professor
BIOL 568 – Bourque L6: 25/1/18
L6: NGS – applications and data analysis
Sequencing Revolution
oSanger NGS : 100s of reactions, 10 000s of bps millions of reactions, billions of bps!
oIncrease in throughput – due to sequencing shorter fragments. Now can sequence longer.
oFalling cost of sequencing
o2001: The Human Genome $3b
o2011: 1000 Genomes Project ~$10 000
o2016-2017: Your genome ~$1000
Applications
1. De novo sequencing: from human genome… to all model organisms… to all relevant
organisms (e.g. extreme genomes)… to ‘all’ organisms.
Slow progression, but increasing with falling cost
Genome 10K/ vertebrate project – must collect all the samples, effort in collection and
data analysis as opposed to the sequencing itself
2. Genome re-sequencing: map genomic structural variations across individuals (to understand
genetic disorders and also susceptibility factors)
Cancer genome sequencing
Agricultural crops
Exome sequencing for Mendelian disease: examples of where technology has been successful
oUsed to be that discovered diseases were common and required large effort. Substantial gap
I knowledge about genes causing rare Mendelian phenotypes
oNow, when not enough people to do linkage studies, these technologies become useful.
oMore information on how gene works mechanistically.
Cancer genome sequencing:
oRef genome on top. Short reads, come in as pairs, map back to reference genome. See which
are identical and which have mutations – point, indel
oNo reads = deletions
oToo many reads = duplication
oCan obtain a full catalogue of mutations
oGrey = all reads. If only one difference more likely to be error in read.
oE.g. mutations in paediatric gliblastoma – cancer in children fewer environmental effects (e.g.
smoking) and build up of mutations
oTook 48 tumours and sequenced exome: large no tumours had exact same mutations
1
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Sequencing revolution: sanger ngs : 100s of reactions, 10 000s of bps millions of reactions, billions of bps, increase in throughput due to sequencing shorter fragments. Now can sequence longer: falling cost of sequencing, 2001: the human genome b, 2011: 1000 genomes project ~ 000, 2016-2017: your genome ~. Applications: de novo sequencing: from human genome to all model organisms to all relevant organisms (e. g. extreme genomes) to all" organisms. Slow progression, but increasing with falling cost. Exome sequencing for mendelian disease: examples of where technology has been successful: used to be that discovered diseases were common and required large effort. I knowledge about genes causing rare mendelian phenotypes: now, when not enough people to do linkage studies, these technologies become useful, more information on how gene works mechanistically. Cancer genome sequencing: ref genome on top. Short reads, come in as pairs, map back to reference genome.
