title: Population genetics of immune-related multilocus copy number variation in Native Americans.
abstract: While multiallelic copy number variation (mCNV) loci are a major component of genomic variation, quantifying the individual copy number of a locus and defining genotypes is challenging. Few methods exist to study how mCNV genetic diversity is apportioned within and between populations (i.e. to define the population genetic structure of mCNV). These inferences are critical in populations with a small effective size, such as Amerindians, that may not fit the Hardy-Weinberg model due to inbreeding, assortative mating, population subdivision, natural selection or a combination of these evolutionary factors. We propose a likelihood-based method that simultaneously infers mCNV allele frequencies and the population structure parameterf, which quantifies the departure of homozygosity from the Hardy-Weinberg expectation. This method is implemented in the freely available software CNVice, which also infers individual genotypes using information from both the population and from trios, if available. We studied the population genetics of five immune-related mCNV loci associated with complex diseases (beta-defensins,CCL3L1/CCL4L1,FCGR3A,FCGR3BandFCGR2C) in 12 traditional Native American populations and found that the population structure parameters inferred for these mCNVs are comparable to but lower than those for single nucleotide polymorphisms studied in the same populations.
authors.affiliation: Departamento de Biologia Geral, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Luciana W
authors.initials: LW
authors.lastname: Zuccherato
authors.affiliation: Departamento de Estatística, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Silvana
authors.initials: S
authors.lastname: Schneider
authors.affiliation: Departamento de Biologia Geral, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Tarazona-Santos
authors.affiliation: Department of Genetics, University of Leicester, Leicester, UK.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Hardwick
authors.affiliation: Department of Molecular Microbiology, Washington University in Saint Louis School of Medicine, St Louis, MO, USA.|Department of Medicine, University of California San Diego, CA, USA.
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Berg
authors.affiliation: Department of Genetics, University of Leicester, Leicester, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Bogle
authors.affiliation: Departamento de Biologia Geral, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Mateus H
authors.initials: MH
authors.lastname: Gouveia
authors.affiliation: Department of Genetics, University of Leicester, Leicester, UK.|School of Health, University of Northampton, Northampton, UK.
authors.forename: Lee R
authors.initials: LR
authors.lastname: Machado
authors.affiliation: Departamento de Biologia Geral, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Moara
authors.initials: M
authors.lastname: Machado
authors.affiliation: Departamento de Biologia Geral, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Rodrigues-Soares
authors.affiliation: Departamento de Biologia Geral, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Giordano B
authors.initials: GB
authors.lastname: Soares-Souza
authors.affiliation: Departamento de Estatística, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Diego L
authors.initials: DL
authors.lastname: Togni
authors.affiliation: Departamento de Biologia Geral, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Roxana
authors.initials: R
authors.lastname: Zamudio
authors.affiliation: Johns Hopkins School of Public Health, Johns Hopkins University, Baltimore, MD, USA.|Asociación Benéfica PRISMA, Lima, Peru.|Universidade Peruana Cayetano Heredia, Lima, Peru.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Gilman
authors.affiliation: Departamento de Estatística, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Denise
authors.initials: D
authors.lastname: Duarte
authors.affiliation: Department of Genetics, University of Leicester, Leicester, UK.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Hollox
authors.affiliation: Departamento de Biologia Geral, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil maira.r.rodrigues@gmail.com.
authors.forename: Maíra R
authors.identifier: 0000-0003-3193-9558
authors.initials: MR
authors.lastname: Rodrigues
mesh_terms: D000483:Alleles; D005260:Female; D005787:Gene Frequency / Q000276:immunology*; D056426:Genetic Loci / Q000276:immunology*; D005828:Genetics, Population; D006801:Humans; D007199:Indians, South American; D008297:Male; D008957:Models, Genetic; D058885:Multilocus Sequence Typing; D010568:Peru; D020641:Polymorphism, Single Nucleotide
keywords: Amerindians; genomic structural variation; immunity; population structure; profiled-likelihood