Population genetics of immune-related multilocus CNV in Native Americans

Luciana Zuccherato, Silvana Schneider, Eduardo Tarazona-Santos, Robert J Hardwick, Douglas Berg, Helen Bogle, Mateus Gouveia, Lee Machado, Moara Machado, Fernanda Rodrigues-Soares, Giordano Soares-Souza, Diego Togni, Roxana Zamudio, Robert Gilman, Denise Duarte, Edward J Hollox, Maira R Rodrigues

    Research output: Contribution to journalArticleResearchpeer-review

    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 parameter , 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, FCGR3B, and FCGR2C) 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 SNPs studied in the same populations.
    Original languageEnglish
    JournalJournal of the Royal Society Interface
    Volume14
    Issue number128
    DOIs
    Publication statusPublished - 29 Mar 2017

    Fingerprint

    American Indians
    population genetics
    loci
    population structure
    assortative mating
    genotype
    founder effect
    homozygosity
    inbreeding
    natural selection
    gene frequency
    methodology
    genomics
    genetic variation

    Keywords

    • Amerindians
    • Immunity
    • genomic structural variation
    • population structure
    • profiled likelihood

    Cite this

    Zuccherato, L., Schneider, S., Tarazona-Santos, E., Hardwick, R. J., Berg, D., Bogle, H., ... Rodrigues, M. R. (2017). Population genetics of immune-related multilocus CNV in Native Americans. Journal of the Royal Society Interface, 14(128). https://doi.org/10.1098/rsif.2017.0057
    Zuccherato, Luciana ; Schneider, Silvana ; Tarazona-Santos, Eduardo ; Hardwick, Robert J ; Berg, Douglas ; Bogle, Helen ; Gouveia, Mateus ; Machado, Lee ; Machado, Moara ; Rodrigues-Soares, Fernanda ; Soares-Souza, Giordano ; Togni, Diego ; Zamudio, Roxana ; Gilman, Robert ; Duarte, Denise ; Hollox, Edward J ; Rodrigues, Maira R. / Population genetics of immune-related multilocus CNV in Native Americans. In: Journal of the Royal Society Interface. 2017 ; Vol. 14, No. 128.
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    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 parameter , 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, FCGR3B, and FCGR2C) 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 SNPs studied in the same populations.",
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    author = "Luciana Zuccherato and Silvana Schneider and Eduardo Tarazona-Santos and Hardwick, {Robert J} and Douglas Berg and Helen Bogle and Mateus Gouveia and Lee Machado and Moara Machado and Fernanda Rodrigues-Soares and Giordano Soares-Souza and Diego Togni and Roxana Zamudio and Robert Gilman and Denise Duarte and Hollox, {Edward J} and Rodrigues, {Maira R}",
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    Zuccherato, L, Schneider, S, Tarazona-Santos, E, Hardwick, RJ, Berg, D, Bogle, H, Gouveia, M, Machado, L, Machado, M, Rodrigues-Soares, F, Soares-Souza, G, Togni, D, Zamudio, R, Gilman, R, Duarte, D, Hollox, EJ & Rodrigues, MR 2017, 'Population genetics of immune-related multilocus CNV in Native Americans', Journal of the Royal Society Interface, vol. 14, no. 128. https://doi.org/10.1098/rsif.2017.0057

    Population genetics of immune-related multilocus CNV in Native Americans. / Zuccherato, Luciana; Schneider, Silvana; Tarazona-Santos, Eduardo; Hardwick, Robert J; Berg, Douglas; Bogle, Helen; Gouveia, Mateus; Machado, Lee; Machado, Moara; Rodrigues-Soares, Fernanda; Soares-Souza, Giordano; Togni, Diego; Zamudio, Roxana; Gilman, Robert; Duarte, Denise; Hollox, Edward J; Rodrigues, Maira R.

    In: Journal of the Royal Society Interface, Vol. 14, No. 128, 29.03.2017.

    Research output: Contribution to journalArticleResearchpeer-review

    TY - JOUR

    T1 - Population genetics of immune-related multilocus CNV in Native Americans

    AU - Zuccherato, Luciana

    AU - Schneider, Silvana

    AU - Tarazona-Santos, Eduardo

    AU - Hardwick, Robert J

    AU - Berg, Douglas

    AU - Bogle, Helen

    AU - Gouveia, Mateus

    AU - Machado, Lee

    AU - Machado, Moara

    AU - Rodrigues-Soares, Fernanda

    AU - Soares-Souza, Giordano

    AU - Togni, Diego

    AU - Zamudio, Roxana

    AU - Gilman, Robert

    AU - Duarte, Denise

    AU - Hollox, Edward J

    AU - Rodrigues, Maira R

    PY - 2017/3/29

    Y1 - 2017/3/29

    N2 - 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 parameter , 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, FCGR3B, and FCGR2C) 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 SNPs studied in the same populations.

    AB - 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 parameter , 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, FCGR3B, and FCGR2C) 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 SNPs studied in the same populations.

    KW - Amerindians

    KW - Immunity

    KW - genomic structural variation

    KW - population structure

    KW - profiled likelihood

    U2 - 10.1098/rsif.2017.0057

    DO - 10.1098/rsif.2017.0057

    M3 - Article

    VL - 14

    JO - Journal of the Royal Society Interface

    JF - Journal of the Royal Society Interface

    SN - 1742-5689

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    Zuccherato L, Schneider S, Tarazona-Santos E, Hardwick RJ, Berg D, Bogle H et al. Population genetics of immune-related multilocus CNV in Native Americans. Journal of the Royal Society Interface. 2017 Mar 29;14(128). https://doi.org/10.1098/rsif.2017.0057