666.09 - Haplotyping Biostatistics 666 Lecture 9 Last...

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Haplotyping Biostatistics 666 Lecture 9
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Last Lecture z Introduction to the E-M algorithm z Approach for likelihood optimization z Examples related to gene counting Allele frequencies estimation Haplotype frequency estimation
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Today: z Other approaches for haplotyping Clark’s greedy algorithm Stephens et al’s coalescent based algorithm z Using haplotypes in association studies
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Useful Roles for Haplotypes z Linkage disequilibrium studies Summarize genetic variation z Selecting markers to genotype Identify haplotype tag SNPs z Candidate gene association studies Help interpret single marker associations May capture effect of ungenotyped alleles
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The problem… z Haplotypes are hard to measure directly X-chromosome in males Sperm typing Hybrid cell lines Other molecular techniques z Often, statistical reconstruction required
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Typical Genotype Data z Two alleles for each individual Chromosome origin for each allele is unknown z Multiple haplotype pairs can fit observed genotype C G Marker1 T C Marker2 G A Marker3 Observation CG TC C T G A G A CT T C A G A G Possible States
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Use Information on Relatives z Family information can help determine phase at many markers z Still, many ambiguities might not be resolved Problem more serious with larger numbers of markers z Can you propose examples? Proportion of Phase Known Haplotypes 0 33 67 100 18 1 5 Markers Unrelateds w/Parents Parents + Sibling
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What if there are no relatives? z Rely on linkage disequilibrium z Assume that population consists of small number of distinct haplotypes z Haplotypes tend to be similar
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Clark’s Haplotyping Algorithm z Clark (1990) Mol Biol Evol 7 :111-122 z One of the first haplotyping algorithms Computationally efficient Very fast and widely used in 1990’s More accurate methods are now available
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Clark’s Haplotyping Algorithm z Find unambiguous individuals What kinds of genotypes will these have? Initialize a list of known haplotypes z Resolve ambiguous individuals If possible, use two haplotypes from list Otherwise, use one known haplotype and augment list z If unphased individuals remain Assign phase randomly to one individual Augment haplotype list and continue from previous step
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Chain of Inference (Clark, 1990)
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Can The Algorithm Get Started?
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This note was uploaded on 12/26/2011 for the course BIO 666 taught by Professor Staff during the Fall '06 term at University of Michigan.

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666.09 - Haplotyping Biostatistics 666 Lecture 9 Last...

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