Effect of transmission model specification on lod score analysis (1)

• The frequency of the abnormal allele, q
• The penetrance values, or probability of being affected conditional on genotype at the disease locus, f0, f1 and f2

One can possess 0, 1 or 2 copies of the abnormal allele with consequent probabilities of affection f0, f1 or f2. (An alternative convention is to denote the penetrance values as f1, f2 and f3.)

Thus a Mendelian dominant disease has penetrance values: 0, 1, 1.

And a Mendelian recessive disease has penetrance values: 0, 0, 1.

If subjects with an abnormal genotype are not necessarily affected then penetrance is incomplete, so appropriate values (for a dominant effect) might be: 0, 0.75, 0.75.

Likewise if some subjects have the affected phenotype despite having a normal phenotype they are said to be phenocopies and appropriate penetrance values might be: 0.0015, 0.75, 0.75.