Computational protocol: Parasites represent a major selective force for interleukin genes and shape the genetic predisposition to autoimmune conditions

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Protocol publication

[…] DT (), Fu and Li's D* and F* () statistics, and diversity parameters θW () and π () were calculated using libsequence (). Coalescent simulations were performed using the cosi package () and its best-fit parameters for YRI, AA, and EU populations with 104 iterations. cosi is a simulation package based on a population genetics model calibrated on empirical data; it therefore allows incorporation of demographic scenarios in simulations.The FST statistic () estimates genetic differentiation among populations and was calculated as previously proposed ().The maximum likelihood ratio HKA test was performed using the MLHKA software () as previously described (). In brief, we used multilocus data of 16 selected genes and Pan troglodytes (NCBI panTro2) as an outgroup (except for IL1F7, where Pongo pygmaeus abelii, NCBI ponAbe2, was used as the outgroup). The 16 reference genes were randomly selected among NIEHS loci <20 kb that have been resequenced across panel 2; the only criterion was that no reference gene rejected the neutral model (i.e., that no gene yielded significant DT). The reference loci used were as follows: VNN3, PLA2G2D, MB, MAD2L2, HRAS, CYP17A1, ATOX1, BNIP3, CDC20, NGB, TUBA1, MT3, NUDT1, PRDX5, RETN, and JUND.LD analyses were performed using Haploview (), and haplotype blocks were identified through an implemented method.Median-joining networks to infer haplotype genealogy were constructed using NETWORK 4.5 (). Estimate of the TMRCA was obtained using a phylogeny-based approach implemented in NETWORK using a mutation rate based on the number of fixed differences between human and chimpanzee or orangutan and assuming a separation time from humans of 6 MY and 13 MY ago, respectively. A second TMRCA estimate was derived from application of a maximum-likelihood coalescent method implemented in GENETREE (). Again, the mutation rate μ was obtained on the basis of the divergence between human and a primate, assuming a generation time of 25 yr. Using this μ and the maximum likelihood θ (θML), we estimated the effective population size parameter (Ne). With these assumptions, the coalescence time, scaled in 2Ne units, was converted into years. For the coalescence process, 106 simulations were performed. All calculations were performed in the R environment (www.r-project.org). […]

Pipeline specifications

Software tools Cosi, HKA, Haploview
Applications Phylogenetics, Population genetic analysis, GWAS
Organisms Homo sapiens
Diseases Autoimmune Diseases, Drug Hypersensitivity, Infection, Dyssomnias