gem-inheritance.md

• how to use those with unknown phenotype and check places where we do use them.

• any additional places to emit warnings?

• there is a --permissive flag (strict=False) that prevents considering family relations in the filtering. default is strict.

• function signatures are: def auto_rec(self, min_depth=0, gt_ll=False, strict=True):

• if there are no affecteds, do we return nothing (and a warning?)

auto_rec

genotypes

• all affected must be hom_alt
• no unaffected can be hom_alt (can be unknown)

strict

• if parents exist they must be unaffected and het for all affected kids (can't have unknown parent).
• if there are no affecteds that have a parent, a warning is issued.

auto_dom

genotypes

• all affecteds must be het
• no unaffected can be het or homalt (can be unknown)
• de_novo mutations are not auto_dom (at least not in the first generation)

strict

• parents of affected cant have unknown phenotype.
• all affected kids must have at least 1 affected parent
• if no affected has a parent, a warning is issued.

questions

• should this be autosomal dominant (mom is unknown):

  3_dad(3_dad;affected),3_mom(3_mom;unknown),3_kid(3_kid;affected) T/C,T/C,T/C

de_novo

genotypes

• all affected must be het
• all unaffected must be homref (or homalt)
• at least 1 affected kid must have unaffected parents

strict

• if an affected has affected parents, it's not de_novo. (see note from Aaron).
• all affected kids must have unaffected (or no) parents
• warning none of the affected samples have without parents.

comp_het

filter by variant:

• affecteds must be het
• unaffecteds are not hom_alt
• TODO: consider case where 1 var of CH is de novo

aggregate by gene, test by pairs:

• phase above sites to remove false (Jessica, we think all sites can be phased; agree?)
• remove candidate pairs iff unaffected has same pair

strict

• ???

mendelian_error

(no strict mode) "opposite homozygotes" == 1 sample hom_ref the other is hom_alt

LOH

kid and one parent are opposite homozygotes other parent is het.

uniparental disomy

parents are opposite homozygotes. kid is homozygote.

implausible de_novo

everyone is homozygote. kid is opposite to parents.

plausible de_novo

kid is het. parents are both hom_ref or both hom_alt.

inheritance.ipynb

"For example, lacking "strict" mode for autosomal recessive, the rule is: all affecteds must be homozygous alternate and anyone that is either unaffected or unknown must not be hom_alt"

Aaron, just double-checking here, do you mean in the non-strict model, the rule would be "all affecteds must be homozygous alternate and anyone that is unaffected must not be hom_alt" (ignoring those that have unknown phenotype)? That's my interpretation of the auto_rec model notes above. In particular this phrase from the notes above for auto_rec -- although I'm not quite sure I understand, it seems the "unknown" part is referring to genotype instead of phenotype:
"no unaffected can be hom_alt (can be unknown)".

@oleraj, I agree, there is confusion about unknown phenotype vs unknown genotype. Trying to address that. I'm looking through the other comments and adjust as well.