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Moleculaire genetica bij hart- & vaatziekten: Een array aan mogelijkheden!
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klinische genetica
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klinische genetica
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Slide 4
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Inschakelen klinisch geneticus
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DNA onderzoek
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Waarom DNA onderzoek?
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Monogene ziekten autosomaal dominant
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Erfelijke (hart- en vaat) ziekten
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Slide 10
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Genome-wide association studies for complex traits: consensus, uncertainty and challenges
Mark I. McCarthy, et al. Nature Reviews Genetics 2008;9:356-369
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Slide 12
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Generation 3
4
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Slide 14
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Results of genetic screening
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Sequencen kandidaat gen
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Variaties in DNA
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AAATATCTATATTCCAATCTCATATTCTTATTTATTTTAATGCTCTTGAACATCTCTAGAAAATGTTTTTCCGTAACGCTTCGA
ATCAATGTGTCTCTGTAGTCCTAATATATTTTGATATTTATATTTGATGCTATGTAGAT[C/G]CAACATTTCTGGGTGTAAAC
TTTCTAGCTATATCTTTGTTTTGCTATTCACTCTAAATGACTCTTTTTGAGTCTCTTGAATTTTACTTTGCCGCCAAATAATAC
TCTCCCACTTTGAAACTAATTGTTATATCTTCTTTCTTTGTACCAGAGTACACTTTAATAGGGGAGTCAGCTTATATATTTTGT
AAGAGATATCTCTAAAGGGGTGGCATTTATGTTGACATCCACCAAGCAGGCTACAATCAGTGCCTCTGTCTGGTTATTTTCCAT
ATGTTTCCTCTCATTTCAGTTAGAAATTGCATGGGCTGAATGGTAACATTTATGGCTCTATGACAAGTTCTTGCAAATAGGTGT
CCAGGTAACAGCTGTGGTCAGATATTCTCTCATAACTTCTGATGCTTATGGAAACAAACTGTGGCTTCTTTATTAGATGTATGG
AAAAGATCCTTGGTGGGAAGAGATGAATGAGAATATGTTTTCAAGTATTGGGACAAACTAGGATTACTTAACATTAGCCCCTCC
AAGCACTGAAAATGTCTTGTTTC[C/T]GATCACTCTTTATATATTGTACTTTTGAAAAGTTCTACATATTCTCAAAACTATTT
GGCCATGAAGGTGGATGACTCCAATGTCTTTTCCAAGCCTATAATTCTACAATTCTATAGAATAAAAAGATCCATCAACAAATC
AACAGAAGCATGTCAGAGGAAGCAATGAATAATATCCTCCAACCTTTTACAGTTTACATAATGGGGATTGGAAACAGCCTAAGT
CATATTTTTTACTATATAATAGCATATTATTGATATTTAACATTTAATTTCCCTGATGTGGATCCTTTGACACGATAACTGAGA
AATTTCTAGTAATCCTTTGGGATCAGTATAATTAGCCACATATTACTGATGAGAAAATTAAAGCCCCAGAGTTCACTGCAGCAT
GGAATAAGTAACTTATTCAACATTTCAAGTTGGGAGAAGCAGAATCAAGAACTTAAACCCAAGTTCTTTGAAGAGATATCTTTA
ATTCTATGTGTGCTGCTCTTCCCACAATATCATATAGCCATATGATCCTACCAGCCGTATGATCCTACCATTAAAATCAGTCTG
GCCATATGAGATGAGCTATATCACTCCTGGGCCCTTGATTTGTCTGATATGTATATGGTGAAACATGCAATATGTATCCGAAGA
ATAAGGAAATAAGTGCGCAGGCATGCACACACACACACACACACACACACACACACACACACAGAATTATCAACAACCTCACTT
CTATTATTCATTGCCTGAAAAAGAAAAGAAAGTCAAACACTTTGCAGAAACCTACATTTTCCCCAGAAACAGAATTACCATGTA
TAAATTAGAGAAAAGATGAATTCCTTTTTAAGGGGCACTAAATGACATATTAGATAGTGACTTTAAACTAATTGTATGTTCTCA
CATATTTGCAAAACATACAGAAAAACTGACCAAATGCATGCTTCTCAATTTTTTATTTTCATAGGCTGAGTGTCTTTTCCCATC
CACATAATTATTTAATTTTTACCCAGTGAAAGTATTTATTGAGGAGTCTCAGATACTATTGTCTATATATATTGAAGAAACCGG
CCTTTTGTTGTTGTTGTTTGTTCTTTAACAGGGTCTCAATCTGTTGCTCAGGCTGGAGTACAGTGGCGTACTACATTTTACTGA
ATATCCTTTTAATGCAGGAGTAGCACTTGGGCAATCTGGAAAATAACTTCCTAAAATATTGGGTTTATTAGGGATATGTTAATT
TGTGAGTAATTTGCAGGAGTTGATCAATCATATCATTATGGAATTTTCTAGCCTGTGATTATAACATCTGTACTGTGCATTTCA
TGTGATTAGTTAAGTCAGAATACTCTAGGCTTTATTGGTTTTTGTTTGGTTGGTTGTTTTTGTTTGTTTGTAAGTAAGCAAGGC
TTTTGAGATGGAGTCTCACTCTGTTGCCCAGGCTGCAGTGCAATGGCCC[G/A]TCTCTGTTCACTTCAACCACAAAAAAATGG
CTGCCTCCTGGAATCAAGCAATTCTCCTGCCTCAGCCTCCTGAGTAGCTAGGATTACAGGCACCCATCACGTTTAGAACAATGC
CACATCTGGCTAATTTTTTATTTTTAGTAGAGACAGGGTTTCACCATGTCAGCCAGGCTGGTCTCAAATTGCATGATGACTGTA
ACTGACCTCAAATGATCTGCCTGCCTCAGCCTCCCAAAGTGCTGGGATTATAGGCATGAGCCACCATGCCTTTAATGTTCTCAT
TGGCCTCTATGCTTTAGATATCACATGTAGCAGAGGAGTTCCCACAATGTTGAAATGATAAGAGCTAGGC GCTGACAAAGATC
ATGTGTTTTCATTACCTCTAGGTCCACCCAACTCACATGAGCAAAAGAATGATCACCTGATGGAATCTCTCTATTGCACACCGG
ATGCCAATTGAAATATAAAGTCACATGGTAGCACATTGCATTAGGAGATACTCGTTCATGGCAAAACTCCCCACAATGTTTGAC
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Frazer et al. Nature Rev Gen 2009
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Bekijken SNPs: SNP array
Whole genome array (WGA)
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SNP Coverage across the Human Genome
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SNP Coverage across the Human Genome
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SNP array: wat kunnen we ermee?
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Slide 24
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Slide 25
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Langste haplotype
Chromosoom 12
PKP2 gen:
Mutatie bevestigd
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Slide 27
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SNP array: wat kunnen we ermee?
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Opzet GWAS
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Slide 30
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Odds ratio’s 1.2
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McCarthy et al. Nature Rev Genetics 2008;9:356-369
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Published Genome-Wide Associations through 6/2009, 439 published GWA at p < 5 x 10-8
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Beperkingen GWAS
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Sterke punten GWAS
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Toekomstige ontwikkelingen
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Toekomstige ontwikkelingen
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Toekomstige ontwikkelingen
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Concluderend/samenvattend
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reserve
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Newton-Cheh et al Nature genetics 2009
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Beschermende faktoren
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Slide 43
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Slide 44
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Hypertrophic cardiomyopathy a sarcomeric disease?
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Slide 46
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Deel deze pagina met collega's en vrienden: