Digenic inheritance pedigree software

For a subset of disorders, the phenotype requires a simultaneous variant at two separate loci. The classical digenic pedigree pattern — unaffected but related parents with multiple affected offspring, then ~25% transmission onwards — is easy to miss if each locus is analysed under autosomal-recessive assumptions. Evagene models the joint two-locus genotype directly.

The classical 25% digenic ratio

An affected parent (Aa;Bb) × an unaffected partner (aa;bb) yields the four offspring combinations Aa;Bb, Aa;BB, AA;Bb, AA;BB in equal proportions. Only the Aa;Bb offspring inherit both pathogenic variants and are affected — 25%. That is the canonical digenic ratio.

Three configurations supported

  • both_het — one pathogenic variant at each locus; the textbook digenic case.
  • one_het_one_hom — asymmetric configurations where one locus requires homozygosity and the other heterozygosity.
  • both_hom — homozygosity required at both loci.

Canonical disorders

Limitations

Both loci are assumed autosomal and unlinked. Genuinely linked digenic loci (loci on the same chromosome with measurable recombination) require a dedicated linkage analysis. The digenic model is not a substitute for an autosomal-recessive model for the many apparently digenic pedigrees that resolve to compound heterozygosity at a single locus on detailed molecular analysis.

Who this is for

Clinical geneticists and ophthalmic genetics services evaluating Usher syndrome, retinitis pigmentosa, and primary congenital glaucoma pedigrees. Genetic counsellors working with families where multiple affected sibs appear from unaffected parents and a standard autosomal-recessive analysis does not fit the transmission data downstream.

See also

Model the digenic pedigree on its own terms

Free access during Alpha.

Join the Alpha Waiting List