Pedigrees and phase

• Lecture 12

How to think through modes of inheritance:

1. How many individuals are affected?
   • Lots - probably dominant
   • Few - probably recessive
2. Does inheritance skip a generation?
   • Yes - probably recessive (carriers do not show the disease)
   • No - probably dominant
3. Is there a bias toward one sex or the other?
   • Yes - probably sex-linked
   • No - probably autosomal
4. Do affected sons always come from affected mothers?
   • Yes - probably X-linked dominant (because the son's X chromosome always comes from his mom)
   • No - probably not X-linked dominant. If there is a male bias, might be X-linked recessive.
5. Do affected fathers always give rise to affected daughters?
   • Yes - probably X-linked dominant (because dad always gives his X chromosome to his daughter)
   • No - probably not X-linked dominant. Could be X-linked recessive if there is a sex bias.
6. Do progeny always have the phenotype that their mother has?
   • Yes - probably cytoplasmic
   • No - not cytoplasmic
7. Do progeny phenotypes skip a generation (have the phenotype of their mother's genotype)?
   • Yes - maybe maternal

With pedigrees, we often want to use disease information to identify a disease marker. These could be single nucleotide variants (SNVs), insertion-deletion variants (indels), copy-number variants (CNVs), or microsatellites/short tandem repeats.

Oftentimes, we know (i) whether the individual is affected or not and (ii) the allele(s) the individual contains at a certain locus.

We need to establish which allele is on the same chromosome as the disease-causing allele (the phase) so we can use these markers as a test for likelihood of an individual inheriting the disease.