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Presentation by Chris Wescott and Angelica Stamegna. Global Variation in Copy Number in the Human Genome. Purpose. We, as humans, are 99.5% similar in our genetic make up 1 in 1,000 bp different Used the dissimilarities across populations, to come up with a whole genome CNV map
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Presentation by Chris Wescott and Angelica Stamegna Global Variation in Copy Number in the Human Genome
Purpose • We, as humans, are 99.5% similar in our genetic make up • 1 in 1,000 bp different • Used the dissimilarities across populations, to come up with a whole genome CNV map • Clinically applicable
CNV classification 5 Types of CNV’s • Deletions • Duplications • Deletions and Duplications at the same locus • Multi-allelic loci • Complex loci that could not be determined
Definitions • CNV (copy number variation)- difference in genome due to deletions, duplications, insertions, and complex-multisite variants that are 1kb or larger • Affymetrix 500K EA- analyzes SNPs • No reference genome
Definitions • CNV (copy number variation)- difference in genome due to deletions, duplications, insertions, and complex-multisite variants that are 1kb or larger • Affymetrix 500K EA- analyzes SNPs • WGTP (Whole Genome Tile Path)- uses large scale clones of a euchromatic section of a reference genome
Methods Compared haplotypes of four different populations 30 parent-offspring from Nigeria (YRI) 30 parent-offspring from Utah, USA (CEU) 45 unrelated Japanese from Tokyo (JPT) 45 unrelated Han Chinese from Beijing, China (CHB)
Discussion • Found 1,447 discrete CNVR’s covering 12% of the human genome • 6-19% of each chromosome • Deletions and Duplications • Not different frequencies but different lengths • Deletions were 1/3 of the size of duplications • Selective pressures
Evolutionary Significance • Gene Families • Linkage Disequilibrium- alleles that do not behave at Hardy-Weinberg • Observed lower linkage disequilibrium for CNV’s than SNP’s • CNV’s happen on transposons • CNV’s might preferentially undergo recurrent mutations • CNV’s might occur preferentially in lower density SNP regions
Diseases and Clinical Significance • CNV’s help with disease study rather than immediate clinical diagnostics • 285 out of 1,961 diseases in OMIM (Online Mendelian Inheritance in Man ) overlap CNV’s • Reliability of using SNP’s to confer disease-related CNVs
Issues • Problems resolving genotype/phenotype correlations • Map itself is variable among populations of people • Human genome variation • No technology available to capture full variation, and multiple steps must be taken
Conclusion • Using SNP genotyping arrays and clone-based comparative genomic hybridization • CNVRs encompass 12% of the genome and encompass genes, disease loci, functional elements and segmental duplications • CNVRs cover more nucleotide content than SNPs