compound heterozygotes

compound heterozygotes

slivar provides machinery for finding compound heterozygotes in trios using phase-by-inheritance. It also reports variant-pairs where 1 side is a de novo. It assumes the input has already been filtered to high-quality variants. The steps are:

1. use slivar to filter to rare heterozygous (or denovo) variants
2. pipe to an effect annotator like bcftools csq, VEP, or snpEff
3. pipe to slivar compound-hets which uses the annotation from VEP to group variants by gene.

The output is a VCF of only comp-het variants with an extra INFO field of e.g.

slivar_comphet=$sample/$gene/$uniqid/$chrom/$pos/$ref/$alt 

which indicates that the current variant is compound-heterozygous in $sample, with the variant at$chrom:$posin$gene`.

Even with a less stringent frequency filter of < 0.005 and no filter on variant function (e.g. allowing synonymous). This can reduce the number of candidate pairs of variants down to about 1 dozen in a standard trio. The $uniqid is an integer that uniquely identifies a variant-pair in a sample.

Usage

Note that by default, the compound-hets tool limits to certain impacts of variants. This can be adjusted using the --skip option. To set so that no variants are skipped, a user can specify, for example --skip NONE.