question on modeling of hereditary disorders of development

[cmungall]

I have a question about modeling using OGMS and individuation of dispositions.

I will take achondroplasia (causative gene FGFR3) as an example, but for purposes here any disease whose underlying pathological process is disrupted pathways during embryonic/early childhood development, but the individual is still considered to have the disease even after the pathological processes are no longer realized.

Consider an individual i with achondroplasia, at various time points from embryo through to adulthood. Conventionally we would say they have have the disease through life. From an OGMS perspective we can identify different kinds of dispositions that are present and are often realized, at different levels from molecular, cellular, through to whole organism. For example:

1. the disposition whose basis is an FGFR3 mutation and is realized as disrupted FGF signaling and abnormal ossification. If the developmental pathways are not activated during adulthood then this disposition ceases to exist (this part is crucial)
2. the disposition whose basis is the physical manifestations of (1); for example the disposition to suffer pain association with back pain, disposition realized as apnea due to physical basis in malformed airways, etc.

If this dispositional analysis is correct, then how many disease instances are there in the patient, according to OGMS, and what are their respective durations?

1. there is a single disease present from embryo through adult, with basis in the FGFR3 mutation. The fact that the disposition is not meaningfully realizable due to the pathways being naturally switched off in adulthood is not a problem. "null" dispositions can exist without any way to realize them.
2. there is a single disease, and it effectively ceases to exist when development stops. However, there is a separate anchondroplasia sensu disorder instance that is a material entity that exists and persists from embryo through to adulthood
3. there are two (or more diseases), the embryonic achondroplasia instance that has the basis in the FGFR3 mutation, and this disease coexists for a time with a separate disease that replaces it, with this disease having a basis in the physical developmental abnormalities caused by the first.
4. some other solution

[cmungall]

A related question is what are examples of some classes that we might expect to see created under "genetic disorder" (aside from the existing two grouping classes for acquired/constitutional)

The definition is A disorder whose etiology involves an abnormality in the nucleotide sequence of an organism's genome.

This strongly suggests that we might expect to find a class "achondroplasia" under here, suggesting approach 2 above. But I may be misreading.

I believe after the COB call many were expecting to find genetic mutations under "genetic disorder" but this doesn't really fit with the definition. They are the mutations, they don't have etiology themselves.

It would really help to have an exemplar OGMS ontology. When I query for ontologies that create their own classes under "disorder" I don't see very many, and none have created their own classes under "genetic disorder"

[scheuerm]

@cmungall I think one of the big advantages of treating disease as a disposition is that it allows for some manifestations to be realized and others not. I also think that the concept of disease course can handle how the likelihood of realization can change over time. So, I would lean toward option #1 above. But I'm not sure what you mean by ""null" dispositions can exist without any way to realize them."