Exome Sequencing represents a much more cost-effective way to study variations with respect to whole genome sequencing and currently constitutes the standard for pre-natal molecular diagnostics. In this study the aim was to identify the variants causing rare Mendelian autosomal diseases – frequency lower than 10−5 - in a set of ten children, having at disposal the exome sequencing data of the individuals and of the corresponding parents.
The analysis was performed based on the following assumptions:
- Disease-causing variants are located on either chro- mosome 21 or chromosome 22,
- Disease-causing variants affect only protein coding regions,
- Alleles segregate independently,
- A set of the possible diseases affecting the individuals, as well as their model of inheritance was given a priori,
- Parental phenotype is unknown,
- High-quality sequencing data is available – probabilistic modelling of SNPs is not necessary.
Variants were searched based on the criteria of rarity, correct allele segregation and deleteriousness using the online Ensembl Variant Effect Predictor (VEP) tool.