High Througput Analysis of Genetic Diverstiy in ADME Related Genes PDF
Preview High Througput Analysis of Genetic Diverstiy in ADME Related Genes
www.inmegen.gob.mx High Througput Analysis of Genetic Diverstiy in ADME Related Genes in the Mexican Population: PGENI Mexico 1st Latin American Pharmacogenomics and Personalized Medicine Congress Dr. Alfredo Hidalgo Miranda INMEGEN, Mexico May 13, 2010, San Juan, Puerto Rico Clinical Trials, Pharmacogenomics and Genomic Diversity Generalization in Clinical Trials is just not possible In the short-term future, clinical trials will have to include genomic information of different populations to get a better evaluation of the drug’s efficacy and safety Clinical randomized trials are increasingly being done outside the US Publicly available population datasets, like the HapMap, do not fully represent genomic diversity of the original populations Unfortunately, not every country has the necessary infrastructure, human and economical resources to perform genomic analyses Given the above, a good starting point is to describe the general genomic diversity in ADME related genes in different and diverse populations worldwide Mexican Mestizos Have a Source of Genetic Diversity not Represented in the HapMap CEU Mestizos YRI ZAP JHC Silva-Zolezzi I, Proc Natl Acad Sci U S A. 2009 May 26;106(21):8611-6. Genotyping and Gene Expression Core Unit: Affymetrix and Illumina Supercomputing and Computational Genomics Genes & markers in the DMET Plus Panel 1,936 functional mutations in 225 genes Markers in all FDA-validated genes DPYD CYP2D6 50 45 NAT1 CYP2C9 CYP450 Phase II NAT2 CYP1A1 enzymes enzymes GSTT1 CYP1B1 UGT1A1 CYP2C19 478 408 UGT1A9 CYP4F2 66 MDR1 PPARD 64 Transcription ABCC1 PPARG Drug regulators & ABCG2 AHR transporters other enzymes SLCO1A2 ARNT SULT1A1 RXRA 637 413 SULT4A1 NR1I2 © PGENI-INMEGEN 2010 Molecular Inversion Probes © PGENI-INMEGEN 2010 PharmacoGenomics for Every Nation Initiative DMET Map: Starting a Global PG map Initial Phase of PGENI’s Worldwide DMET Map Genotyping of more than 700 individuals from around the world 7 designed regional centers in 4 continents 20 different human populations © PGENI-INMEGEN 2010 PGENI DMET Map: Starting a Global PG map Jordan 1 population China 2 populations Ghana 2 populations Mexico 2 populations India 2 populations Brazil 3 populations South-Africa 5 populations © PGENI-INMEGEN 2010
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