Medical Genomics Flashcards
When was the human genome mapped?
2003
When did next generation sequencing begin?
2010->
What is NGS?
Next generation sequencing
The rapidly advancing technology that makes it economically viable to sequence individuals rather than species
What % of the genome is the exome?
1%
What does studying the transcriptome RNA allow us to study?
Gene expression
Gene fusions
Splice variants
How many base pairs in a genome?
About 3200 million
How many base pairs in an exome?
5–70million
Negatives of exome sequencing
Only picks up 85% of disease causing variants
Requires additional sample prep
No assessment of non coding regions
Simple repeats, GC rich and highly homologous regions are poorly captured
Clinical exome develops over time
Negatives of genome sequencing
Much more expensive
Massive data (storage?)
Interpretation more expensive and difficult
Steps in exome sequencing
Genomic DNA Shotgun library-> fragments Rehybridisation Pull down and wash Captured DNA is sequenced Mapping, alignment and variant calling
What does variant calling rely on?
Accurate alignment to a reference sequence from the Human Genome Reference
No read is the full gene
Who should be sequenced?
Distantly related concordantly affected individuals (share very few mutations)
Closely related discordant individuals (very few differences)
What is a compound heterozygote?
The presence of two different mutant alleles at a particular gene locus, one on each chromosome of a pair
Different mutations in mum and dad but on same allele
Offspring has no functioning copies of that gene
What does consanguineous mean?
The quality of being descended from the same ancestor as another person.
What are the 6 main types of mutations?
Inherited (autosomal recessive, autosomal dominant, X linked recessive, consanguineous autosomal recessive)
De novo
Mosaic
What is needed for bioinformatics?
4Gb data for each sample
Biologists skilled in programming
IRIDIS4 supercomputer
