BMS2042 Lecture Notes - Lecture 16: Blastocyst, Germline Mutation, Zygosity
30 May 2018
School
Department
Course
Professor
Week 10. Genomics and transgenic techniques, and
Transgenic and knockout mice (gene targeting
technology)
GENOMICS AND TRANSGENIC TECHNIQUES
• Molecular genetics:
o Deciphering gene codes
o Discovering genes associated with disease
• Genome: hereditary information encoded in the DNA of an organism including both protein
coding an non-protein coding sequences
o <2% of 3.2 billion bp make up protein coding sequences
o ~250,000 protein coding genes
o >50% is in some form of repetitive sequence
o 99.9% of genome is the same in all people
-> variation through SNP and CNV
o Genes are not evenly distributed through genome eg. chromosome 1 = 2968 genes, Y
has 231
• HGP (human genome project):
o Make a complete and accurate sequence of the human genome
o Identify all genes and understand their roles
o Personalised medicine
o Role in disease
o 0.01% error rate
o 96% coverage euchromatic region (gene rich regions)
o 350 gaps
o 25 years since completed
o Interpretation of OMIM (online mendelian inheritance in man)
Functional/structural/personal/cancer genomics
pharmacogenomics
o SNP/CNV : HapMap
o Improved gene technology
find more resources at oneclass.com
find more resources at oneclass.com
• ORF = open reading frames
• ENCODE (encyclopedia of DNA elements)
o 1-2% genome originally identified as functional genes (proteins, functional RNA,
regulatory RNA)
o 50% is dynamic/repetitive
• Biggest gene: encodes for dystrophin which is 2.4 million bp long, encodes for structural protein
• Gene with most number of introns: titan with 234 introns
• Pharmacogenomics:
o Defined as how an individuals genome affects the response to a drug
o Used to personalise treatment
o Diagnostic applications
o Used to assess who may have experienced adverse side-effects to certain drugs
• Genome sequencing technology:
o Originally a mapping approach which was slow
o Shotgun approach to sequencing developed
o Archon genomics X prize: first team to automatically sequence 100 human genomes
(>$1000 per genome sequenced)
• Evolution of sequencing techniques:
o $1/base -> $0.01/base
o High throughput
find more resources at oneclass.com
find more resources at oneclass.com
o Automated
o Faster
o Cheaper
o Error reduction
o Single cell genome sequencing
• What is not a genome sequencing technique?
o Trasriptois looks at what’s trasried, MRNA owards
-DNA microarray data
-mass spectrometry
-northern blot
o Preotomics:
-estimated 150,000-200,000 proteins from 20,000 genes due to splicing
-also investigates post translational modification, variation between cells
-mass spec
• Working out gene/protein function
o How do you physically get gene into cell?
o How do you get gene into each cell of the organism
o How do you make the change stable?
-> best way is to integrate into actual genome
o How do you improve the chance of success?
-> wo’t e fiaiall feasile if ot high hae
o Are there off target effects?
• Forward genetic tools: random mutagenesis
o Use mutagen to induce higher rate of random mutations
o Eg. ENU in mice
find more resources at oneclass.com
find more resources at oneclass.com
