ABSTRACT
Cosegregation refers to the inheritance of disease-causing mutations together with clinical diseases in a family. The analysis of cosegregation of variants with disease is a powerful tool for gene discovery research, and diagnostics. In the context of exome and genome sequencing, datasets are usually relatively small and encompass nuclear families or parts thereof. Often, variants or genes are filtered to those showing a pattern of inheritance that matches the disease diagnosis. For instance, if we are considering an autosomal dominant disease, then a variant that is not present in a patient or that is present in an unaffected relative can usually be excluded from further analysis. In this chapter, we will show how the analysis of cosegregation in nuclear families (e.g., parents and siblings) can be used to filter genes and variants in WES/WGS studies. The family structure is recorded in PED files, and we will begin the chapter with an explanation of the PED file format and the symbols used for describing a pedigree.
