Genomics Flashcards
genome
the entire dna content of an organism or cell
exome
the region of the genome that codes for proteins
% of the genome which is exome
2%
Non-coding DNA
the rest- includes regulatory sequences and ‘junk’
Epigenome
modifications to the genome e.g. methylation and histone acetylation which may regulate its function
karyotype
chromosomal content of a cell
genomes
vary from person to person
what make genomes different
nucleotide polymorphisms
nucleotide polymorphisms
SNPs, indels and repeats
how many known SNPs in human genome
10 mill
how many changes to reference genome coding sequences per person
10,00
how many loss of function per person
250
an example o how karyotype links to phenotype
CML
- ABL
- easy to see down a microscope
simple monogenic disorders e.g.
CF
-inheritance pattern suggested single gene defect
-
CF is
autosomal recessive
genetic linkage
a measure of how resistance to recombination marker and phenotype are
- focuses on a very small chromosomal regions
Tom Satinford
a progeria athlete from exeter
how could we find out what condition Tom has
1) trio analysis
2) exome sequences
Deep sequence both parents- in this case exome only. Deep sequence the probing (tom)- anything new?
example of polygenic diseases
diabetes, alzheimers
polygenic disease are much
more complicated
with polygenic disease there is
some heritable risk, not guaranteed to inherit though. Combination of genetics and the environment
with polygenic diseases what could we used to know which genes are involved
GWAS
GWAS
genome wide association study
GWAS looks for
SNPs that are ‘over represented’ in disease patients
SNPs do not
have to be genes- can act as a marker for a different kind of mutation/regulatory region
if SNPs are more common then you’d expect
you would expect nearby genes are involved
why is GWAS useful to science as well as medicine
often several genes identified which are known to be involved in a shared pathway. gives a clue into the rise mechanism.
Help us in choosing a drug target
prospective cohort study
allows genotype to phenotype correlation
mendelian randomization
determine causality for ons studies. Our genotype is randomly assigned at birth. not influenced by confounding factors.
e.g. is smoking bad for you
- there are SNPs associated with heavy smoking
- assume SNPs aren’t causal for death
- but are they associated with death?
GWAS does not
explain all common disease
e.g. environment must also be important (lung cancer)
what about epigenetic changes
changes to DNA that do not affect its base sequence are thought to be environemntal
you can..
can map methylation in a genome
- some abnormal methylation patterns correlate with certain disease e.g. Alzheimer’s and cancer
CRISPR can help
provide answers as to where genes are being turned on or off to cause disease, or if its cause or effect
polygenic diseases often have
environmental elements- leading to epigenetic changes
genome sequencing and GWAS used to identify
defective/ contributory genes
big data sets being use to
establish correlation
