Misuratore fiscale a turbina CGT - CGT Turbine primary measurement meters
Carlos Alvarez BCMM/CMHG/CGT Joint Meeting September 15 th , 2011
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Transcript of Carlos Alvarez BCMM/CMHG/CGT Joint Meeting September 15 th , 2011
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Carlos AlvarezBCMM/CMHG/CGT Joint MeetingSeptember 15th, 2011
Multidimensional genomics in mammalian cohorts
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Lab background• PhD, mol. genetics of vision (Drosophila)• Postdoc, mol. neurosci. & genomics (rodents)• Lab Head, Novartis (hum., rodent)Themes – evolution, bioinformatics, genomics
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Genetics
≥ 15,000 YA
150-200 YA
400 breeds
Why study CNV in dogs?
• 450 inherited diseases• Dog genome similar to human• 5-7X shorter lifespan v. humans• 75M dogs in USA• Low intra-breed variation; high inter
Variation(morphological, physiological & behavioral)
▪ 65X difference sm/largest breeds (wt.)
▪ ~250X smallest/largest individuals
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Ongoing genetic studies in dogsa. DNA copy number variation (CNV; custom 1M feature)
b. Genome wide association in complex genetics (12x175k SNP)
Genome Res. 2008
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Integrating CNV and SNP haplotypes
Rowell et al. TMM 2011
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Kerns et al. (2007) Genetics 176:1679.
KBlack kbrindle kyellow> >
Coat color: Dominant Black locus
In humans, pigmentary mosaicism (not mutation, but effect of two genetic cell types)
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CNV explains brindle
Dominant black gene
Identified CNV associated with brindleand developed first genetic test
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Approach (for germ line):1. High OSA risk pop. w/ 100X reduced variation2a. Allele-wise GWA analysis 2b. Dimensional reduction of allele ratios
Complex genetics of osteosarcoma
SNP Chr PositionBICF2S23318678 3 22278940BICF2P756511 3 34630563BICF2S22958963 3 34806577BICF2S23713946 5 3741194G320f26S259 5 3814438BICF2P959468 5 24064707BICF2S23647041 5 25563084BICF2S23746914 6 71831263BICF2S22933176 6 72089371BICF2P643804 6 72282176BICF2P878053 6 72314083BICF2S23332924 6 72453644G439f54S214 7 23851944TIGRP2P97627 7 49152204BICF2P989771 9 27058611BICF2P395540 12 67862864BICF2P998637 14 39888317BICF2S23147465 14 51418412BICF2S2339350 18 23106621BICF2S23348607 18 23130080BICF2P950849 18 37553821TIGRP2P335678 25 54551661BICF2P691768 28 42235397BICF2P681391 31 39698895BICF2P623089 34 30054450
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Multidimensional genomics in longitudinal cohorts
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Conclusion
Longitudinal cohorts will enable
determination of genetic alterations (SNPs,
CNV) contributing to disease initiation,
progression and promotion
… and of the relative contributions of
genetics and environment