Estimation of carrier of Mendelian disorders.

Question

[yama12408]

I read exome sequences from several individuals and performed variant calling.

As a next step I am going to annotate all variants with the causative mutations for inherited disease or disease-susceptibility gene, which have been previously reported.

Is there any software to perform this analysis?

Alternatively is there any service or company to do this?

Answer 1

[iraun]

To annotate your variants, you have a wide range of possibilities.

• I usually start with SnpEff to annotate variant and predict their effect (aa changes, STOP codons... etc).
• Also, I would recommend you to give a try to **ANNOVAR, which can functionally annotate genetic variants attending to different criteria (gene-based annotation, region-based annotation...).
• Finally, GEMINI (GEnome MINIng): it is a powerful system for exploring genetic variation for for disease and population genetics. You can load your VCF file to GEMINI database. Each variant is automatically annotated by comparing it to several genome annotation (ENCODE tracks, UCSC, OMIM, dbSNP, KEGG...). To use GEMINI it is highly recommended to know the basics of SQL.

[DG]

Just to add some more detail, GEMINI requires you to annotate a VCF first with SnpEff or VEP (Ensembl). My workflow is SnpEff -> GEMINI as I prefer SnpEff's annotations and native handling of VCF in and VCF out to Annovar (Annovar has only recently added proper VCF support).

Some of the annotations SnpEff and GEMINI add that will be of interest to the OP's original question are the OMIM and ClinVar related annotations.

[iraun]

Yes, you are right, I forgot that GEMINI requires previously SnpEff annotated vcf file.