Mendelian inheritance

Just a mechanical developmental hiccup.

But a cleft palate is also a recognized shared phenotypic feature across hundreds of distinct severe Mendelian genetic disorders.

Ah, I see.

CP operates through the exact same mechanism.

It can occur in isolation due to mechanical perinatal factors like a lack of oxygen, but it is also a convergent symptom of 89 distinct Mendelian diseases.

So for the pediatric neurologist and more importantly, the patient and their family, this fundamentally changes the entire care pathway.

It absolutely does.

So

And I would say, "No, we don't only care about LDL because of drugs.

We care about drugs because of biology, and we care about drugs because of, of observational studies, Mendelian randomization genetic studies, randomized controlled studies all pointing in the same directions, direction and showing us less heart attacks and less stroke consistently across different populations."

Well, and, and, but we also will say when we're wrong.

We used to care a lot about HDL.

Mm.

Um, I think the biggest thing that can happen in insurance, but they don't quite get it yet, is, uh, is protecting us against severe Mendelian diseases.

This is something where they could get a hundred fold return on investment within two years, which is kind of their magic number.

If they can't get it back in two years, then they're worried that all their people are gonna...

Well, because we've way beyond nineteen seventy when I started [laughs], we have a multitude of clinical trials that provide the evidence showing us, so what are the etiologic agents of atherosclerosis, and we have a ton of observational trials, suggestive data.

We have a bunch of randomized controlled data, which is level one evidence, and now we have the genetic data, the Mendelian randomization trials.

And if you put that all together, and the major medical societies have done that, the first was the European Atherosclerosis Society back in...

They did papers, I believe it's two thousand seventeen, May, and part two, two thousand twenty, where they, they declared LDL cholesterol and, of course, ApoB is causal of this disease based on those type of trials.

Someone with loads of disease, throw the kitchen sink at them.

Someone who, at the other end of the spectrum, you're talking about primordial prevention, a little bit of management can go a very long way.

Tom referred to some of the evidence tangentially as, you know, from the Mendelian randomization data that supports that kind of long-term approach.

That's not interventional data, that's observational data, but it's very powerful information that I think we can take to how we manage care for patients over decades.

It was at this point that Mendel's discoveries came to the rescue.

Working on the Mendelian lines already explained, Biffin at Cambridge crossed red fife with many of the best English varieties.

From one of the crosses, he was able to isolate a new variety in which are combined the strength of red fife and the vigor and cropping power of the English parrot.

This variety, known as Burgoyne's fife, has been grown and distributed by members of the Miller's Association.

His work remained practically unknown till 1900.

Mendelism.

There are three fundamental ideas in Mendelism.

The first is the idea of unit characters.

And this requires a little patience.

But the most important point is that the unit characters or their factors behave as if they were definite entities, like the radicals in chemistry, which can be shuffled about and distributed to the offspring in some degree independent of one another.

Thus, in the lineage of the night blind, it was not every individual that showed the peculiarity, but only a certain proportion in each generation.

In his masterly work on Mendelism, Professor R.C. Punnett refers to a unit character as follows.