personalized medicine Flashcards
an individuals entire dna sequence
genomics
what did we see in the HGP
transcription factors are more important than the differences in our genes
we found similarities in complex regions
what did the HGP map
humans genome
when was the HGP
1999-2003
what did the Hap map do
separated what was actually relevant from the HGP
the ____ found that there is greater variability _____ and ethnic group than ______ ethnic groups
hap map, within, btwn
the human genome project expected to identify _____ genes, but actually found _____
35,000
22,000
as humans, we are ______ % identical
over 99
whole genome sequencing sequences _______
entire human genome which is about 6 billion nucleotides
whole exome sequencing sequences _______
exons in the human genome which is about 9-12 million nucleotides
GWA studies/ SNPs focus on_____
specific bases in the DNA sequence
we use this genomic technology in research
whole genome
we use this genomic technology in clinical practice
whole exome
we use this genomic technology in DTC
GWAS/SNP
what do we look for in clinical genetic testing
single gene sequencing and mutations in specific genes
is single gene sequencing expensive?
yes! it’s about $600-4000
if we cant find a specific gene cause in a family, what do we do
screen ALL family members via EKG and MRA
what does VUS stand for
variant of unknown significance
what are some limitations of single gene sequencing
we get VUS 3-6% of the time and not all labs interpret the same
we have a fast turn around time for single gene sequencing, but sometimes it takes _____ hours to interpret the results
over 300 hours
exome sequencing identifies a cause in ____% of cases
40
what limits finding an answer in exome sequencing
methodology, phenotypic info given, interpretation of variants (sometimes we dont know what every variant does)
what happens in methodology
sequencing reads 100-250 bp at a time then a computer organizes the reads
limitations of methodology and it only reading 100-250 bp
we depend on computers to arrange info and it does not distinguish between close copies of regions
computers that arrange info in methodology have a ____% error rate which is __________
0.1%, unacceptable
what does exome/genome sequencing not detect?
pseudogenes, trinucleotide repeats, large genomic rearrangements, large deletions and duplications of whole genes, methylation abnormalities
methodology is confirmed by this
traditional sanger sequence
we dont need to test all 22000 genes so we other data to help us know where to look. what other data does the lab need
mri findings, muscle biopsy findings, clinical course, FH
most well described genes have a ____% VUS rate
3-16
how do labs interpret genetic results
case reports and data bases
true or false: some genes have no known function
true
a patients _____ dont change over time, but _____ may
genes; interpretation
with exome sequencing, we only sequence about ____% of the entire genome
1-2
if a gene is labeled as ______ it might be benign or pathogenic
VUS
before doing gene sequencing in clinical practice, what do pt have to go through
pre-test counseling
what 2 types of incidental findings may we have on a genetic test
carrier status or medically actionable genes
can the family pick if they want additional information about a genetic test
yes
when doing a genetic test, what kinds of carrier statuses might we find
someone with a common recessive disorder like CF or tay sachs which may impact reproduction for a family
what medically actionable genes can be found on a genetic test
treatable childhood or adult disorders, untreatable child disorders, or childhood cancer syndromes
what is NOT included on a genetic test
adult onset disorders like alzheimers and parkinsons
are epilepsy disorders in kids treatable?
yes
how much does it cost to sequence an exome
$8000
this genetic test is a last resort
WES
could identifying a cause affect trmt?
yes, bc then we can manipulate the basis of the disease via over or underexpression instead of the sx
what are GWAS/SNP
when we look at a whole population to see if we can figure out a pattern for who has sx and who does not… COMPLEX
GWAS/SNP are done for these types of diseases
more common ones; they quantify risks for individuals/groups
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