title: Integrated genotype calling and association analysis of SNPs, common copy number polymorphisms and rare CNVs.
abstract: Accurate and complete measurement of single nucleotide (SNP) and copy number (CNV) variants, both common and rare, will be required to understand the role of genetic variation in disease. We present Birdsuite, a four-stage analytical framework instantiated in software for deriving integrated and mutually consistent copy number and SNP genotypes. The method sequentially assigns copy number across regions of common copy number polymorphisms (CNPs), calls genotypes of SNPs, identifies rare CNVs via a hidden Markov model (HMM), and generates an integrated sequence and copy number genotype at every locus (for example, including genotypes such as A-null, AAB and BBB in addition to AA, AB and BB calls). Such genotypes more accurately depict the underlying sequence of each individual, reducing the rate of apparent mendelian inconsistencies. The Birdsuite software is applied here to data from the Affymetrix SNP 6.0 array. Additionally, we describe a method, implemented in PLINK, to utilize these combined SNP and CNV genotypes for association testing with a phenotype.
authors.affiliation: Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA. jkorn@broad.mit.edu
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Korn
authors.forename: Finny G
authors.initials: FG
authors.lastname: Kuruvilla
authors.forename: Steven A
authors.initials: SA
authors.lastname: McCarroll
authors.forename: Alec
authors.initials: A
authors.lastname: Wysoker
authors.forename: James
authors.initials: J
authors.lastname: Nemesh
authors.forename: Simon
authors.initials: S
authors.lastname: Cawley
authors.forename: Earl
authors.initials: E
authors.lastname: Hubbell
authors.forename: Jim
authors.initials: J
authors.lastname: Veitch
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Collins
authors.forename: Katayoon
authors.initials: K
authors.lastname: Darvishi
authors.forename: Charles
authors.initials: C
authors.lastname: Lee
authors.forename: Marcia M
authors.initials: MM
authors.lastname: Nizzari
authors.forename: Stacey B
authors.initials: SB
authors.lastname: Gabriel
authors.forename: Shaun
authors.initials: S
authors.lastname: Purcell
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Daly
authors.forename: David
authors.initials: D
authors.lastname: Altshuler
mesh_terms: D000465:Algorithms; D002877:Chromosomes, Human / Q000235:genetics*; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D005260:Female; D018628:Gene Dosage / Q000235:genetics*; D015894:Genome, Human; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008297:Male; D008390:Markov Chains; D015233:Models, Statistical; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012984:Software
chemical_list: D004247:DNA
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