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Genetica van HDL-metabolisme: klinische relevantie voor (toekomstige) therapeutische strategieen
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Dia 2
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Clinical Cardiovascular Events Reported in Clinical Trials
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Why has the risk of CAD not been reduced by virtually 100% by the current treatment programs?
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CHD Risk According to HDL-C Levels Framingham Study
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HDL-c is a target for therapy…
But where to start…?
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7
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HDL family genetics: 10 years “AMC” results
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Are we done with family studies?
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Clinical Validation is Key
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Validated Targets Are Critical
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Genetics approaches: concepts
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GWAS
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GWAS; the picture
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GWAS in lipids; done deal...
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Yes, it is relevant.
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What to do with the 95 loci?
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Dia 18
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PCR based strategies
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Novel Approach Next Generation Sequencing.....
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NGS-SBS technique
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PCR vs NGS
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Feed the Monster
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Dry Data Sheet
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Candidate Genes
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Herman, Hovingh et al Nature Methods 2009
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How well are we in enrichment of subgenome? (fold enrichment)
Goal: 100.000 out of 3x109 nucleotides; 1 in 30.000 (30.000 fold enrichment)
Capturing on filter:
70% aligned to subgenome, 89% of these alligned within amplimers: > 20.000 fold enrichment
99.8% of reads within amplimers read depth >20
What can we detect (SNPs / CNV Detection)?
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Novel non syn mutations
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SNPs/CNVs
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Summary NGS
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Next 10 years
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Acknowledgments
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