L14 - diagnosing genetic diseease 2 Flashcards
how much of genome is cnv
12% (more than snp)
how many cnv per ind
20
estimate cna and rare disease
8-15% of cause rare disease
underlie gen div and suseptibility of complex disease
what detection mech is the gold standard for confirmation of specifc mut
sanger based cycle seq
what are the adv of sanger based cycle seq
easy
cheap
targetedd mut and gene are fully categorised
what are the dsadv of sanger based cycle seq
laborous for big genes
msises whole exon de and dup
no genome wide coverage
how are mut detected in known conditions
- check if predefined nt altered = sanger/MLPA/ARMS
- scan whole genome
wha is ARMS (amplification refractory mut system ) used to detect
cf mut /screens
adv of ARMS
can distinguish homo/hetero for all mut
reliable
simple protocol
multiple mut can be detect in sgl analysis
what do whole genome seq cover
cover 95-98% of genome
inc high GC content and repeat regions / centromeres/telomeres
adv of whole genome seq
uniform genome cover
better determination of cnv/rearrangements
variatns in reg regions
adv of whole exome seq
focus on smaller amout of genome (2%) but this has 85% variatns of mendel disease
quicker
cheaper
easier to analyse as less data
what are the clinical features of charge syndrome
coloboma/heart malform/atresia of chonnae/retard growth and dev
describe the genetic studies of charge syndrome
normal karyotype
use aCGH - found 8q12 del of 17 genes/FISH verified/de novo occurence
what the disease mech of charge syndrome found to be through sanger seq
the del results in truncated/non-functional CHD7 or 4disrupts chromatin remocel and regen of gene expr
chnage in gene expr during emb dev - charge clinical features
show not micro del but monogenic
