zCall: a rare variant caller for array-based genotyping

Abstract

Summary: zCall is a variant caller specifically designed for calling rare single-nucleotide polymorphisms from array-based technology. This caller is implemented as a post-processing step after a default calling algorithm has been applied. The algorithm uses the intensity profile of the common allele homozygote cluster to define the location of the other two genotype clusters. We demonstrate improved detection of rare alleles when applying zCall to samples that have both Illumina Infinium HumanExome BeadChip and exome sequencing data available.

Quality control, imputation and analysis of genome-wide genotyping data from the Illumina HumanCoreExome microarray

“…Variant MAF has many effects on later analysis, as allele frequency is associated with time since mutation, the structure of local linkage disequilibrium (LD) and the relative size of the association statistic [15,16]. The chances of an error in genotype calling increase with decreasing MAF, as the certainty of manual and automatic clustering falls with fewer variants in each cluster [17]. At the most extreme level, if all but one variant cluster together, it is difficult to assess whether the lone variant is truly a different genotype, or whether it is a missed call.…”

“…Typically, many studies define rare single nucleotide polymorphisms (SNPs) as having a MAF <1%, which has historical roots in the HapMap project [19]. It is worth noting that the exonic content of the HumanCoreExome chip was specifically designed to target coding variants, with much of this content having a population MAF <1% [17]. Therefore, using this microarray in smaller cohorts and imposing a MAF cut-off of 1% or higher will result in discarding most of the exonic content.…”

Rare variant genotype imputation with thousands of study-specific whole-genome sequences: implications for cost-effective study designs

“…9,10 Genotype calling was performed using the Illumina GenCall algorithm (Illumina, San Diego, CA, USA), and an additional 2968 rare variants were called for HumanExome using Zcall. 11 A subset of 1072 samples was also previously genotyped with Affymetrix 6.0 (Affymetrix, Santa Clara, CA, USA). 12 After performing quality control checks (see Supplementary Information and Supplementary Table S1 for details), we used the quality-checked (QCed) autosomal markers from the HumanOmniExpress, ImmunoChip and CardioMetaboChip arrays as baseline genotypes to impute variants detected through sequencing, as described below.…”

Independent Replication and Meta-Analysis for Endometriosis Risk Loci

“…Data were then further processed by zCall (Goldstein et al, 2012), a rare variant caller, in an attempt to recall missing genotypes. Following manufacturer's guidelines and the protocols developed for the Exome chip data, quality control measures were applied to the Belgian GWA data.…”