Sandwalk: Polycystic Liver Disease

Thursday, September 27, 2007

Polycystic Liver Disease

Polycystic liver disease (PLD) is associated with the formation of multiple cysts of various sizes in the liver. Sometimes it causes enlargement of the liver and abdominal pain but in most cases there are no symptoms and the patient may be unaware of any problem.

This disease is not the same as the often fatal polycystic kidney disease (PKD) [OMIM 173910] although patients suffering from kidney failure due to PKD will often have cysts in their liver as well.

PLD is inherited as an autosomal dominant trait, which means that you will have liver cysts even if you only inherit one mutant allele from one parent. There are probably several different genes that can be affected but two genes have been identified and characterized [OMIM 174050]. One of them is the SEC63 gene on chromosome 6q21 [OMIM 60648][Entrez Gene 11231]. This gene encodes one of the components of the ER membrane translocon. This is the pore through which newly synthesized is threaded following attachment of the ribosome/signal-recognition-particle complex [Signal Hypothesis] [Human Genes Involved in the Signal Hypothesis Pathway]. The defect in SEC63 probably interferes with sorting and secretion of proteins in the liver and this is what causes the cysts.

The Online Medelian Inheritance in Man (OMIM) database at Johns Hopkins University is one of the best databases in the world.
The known alleles are null mutations meaning that they disrupt synthesis of the protein. It appears that the presence of one defective copy of the SEC63 gene has no effect on normal development or secretion in most tissues but does have a non-lethal effect in liver cells.

The other gene that's associated with polycystic liver disease is PRKCSH, a gene that encodes the β subunit of glucosidase II [OMIM 177060]. This protein plays a role in the glycolsylation of proteins in the endoplasmic reticulum [glycosylation]. Since glysosylation is requried for protein sorting and secretion, it is likely that interference in that process is resposible for liver cycsts. This is the same process that's defective in SEC63 mutants.

[Photo Credit: OSF Heathcare]

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The old argument of design in nature, as given by Paley, which formerly seemed to me to be so conclusive, fails, now that the law of natural selection has been discovered. We can no longer argue that, for instance, the beautiful hinge of a bivalve shell must have been made by an intelligent being, like the hinge of a door by man. There seems to be no more design in the variability of organic beings and in the action of natural selection, than in the course which the wind blows.Charles Darwin (c1880)

Although I am fully convinced of the truth of the views given in this volume, I by no means expect to convince experienced naturalists whose minds are stocked with a multitude of facts all viewed, during a long course of years, from a point of view directly opposite to mine. It is so easy to hide our ignorance under such expressions as "plan of creation," "unity of design," etc., and to think that we give an explanation when we only restate a fact. Any one whose disposition leads him to attach more weight to unexplained difficulties than to the explanation of a certain number of facts will certainly reject the theory.

Charles Darwin (1859)

Science reveals where religion conceals. Where religion purports to explain, it actually resorts to tautology. To assert that "God did it" is no more than an admission of ignorance dressed deceitfully as an explanation...

Peter Atkins

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The world is not inhabited exclusively by fools, and when a subject arouses intense interest, as this one has, something other than semantics is usually at stake. Stephen Jay Gould (1982)
I have championed contingency, and will continue to do so, because its large realm and legitimate claims have been so poorly attended by evolutionary scientists who cannot discern the beat of this different drummer while their brains and ears remain tuned to only the sounds of general theory. Stephen Jay Gould (2002) p.1339
The essence of Darwinism lies in its claim that natural selection creates the fit. Variation is ubiquitous and random in direction. It supplies raw material only. Natural selection directs the course of evolutionary change. Stephen Jay Gould (1977)
Rudyard Kipling asked how the leopard got its spots, the rhino its wrinkled skin. He called his answers "just-so stories." When evolutionists try to explain form and behavior, they also tell just-so stories—and the agent is natural selection. Virtuosity in invention replaces testability as the criterion for acceptance. Stephen Jay Gould (1980)
Since 'change of gene frequencies in populations' is the 'official' definition of evolution, randomness has transgressed Darwin's border and asserted itself as an agent of evolutionary change. Stephen Jay Gould (1983) p.335
The first commandment for all versions of NOMA might be summarized by stating: "Thou shalt not mix the magisteria by claiming that God directly ordains important events in the history of nature by special interference knowable only through revelation and not accessible to science." In common parlance, we refer to such special interference as "miracle"—operationally defined as a unique and temporary suspension of natural law to reorder the facts of nature by divine fiat. Stephen Jay Gould (1999) p.84

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My own view is that conclusions about the evolution of human behavior should be based on research at least as rigorous as that used in studying nonhuman animals. And if you read the animal behavior journals, you'll see that this requirement sets the bar pretty high, so that many assertions about evolutionary psychology sink without a trace.

Jerry Coyne
Why Evolution Is True

I once made the remark that two things disappeared in 1990: one was communism, the other was biochemistry and that only one of them should be allowed to come back.

Sydney Brenner
TIBS Dec. 2000

It is naïve to think that if a species' environment changes the species must adapt or else become extinct.... Just as a changed environment need not set in motion selection for new adaptations, new adaptations may evolve in an unchanging environment if new mutations arise that are superior to any pre-existing variations

Douglas Futuyma

One of the most frightening things in the Western world, and in this country in particular, is the number of people who believe in things that are scientifically false. If someone tells me that the earth is less than 10,000 years old, in my opinion he should see a psychiatrist.

Francis Crick

There will be no difficulty in computers being adapted to biology. There will be luddites. But they will be buried.

Sydney Brenner

An atheist before Darwin could have said, following Hume: 'I have no explanation for complex biological design. All I know is that God isn't a good explanation, so we must wait and hope that somebody comes up with a better one.' I can't help feeling that such a position, though logically sound, would have left one feeling pretty unsatisfied, and that although atheism might have been logically tenable before Darwin, Darwin made it possible to be an intellectually fulfilled atheist

Richard Dawkins

Another curious aspect of the theory of evolution is that everybody thinks he understand it. I mean philosophers, social scientists, and so on. While in fact very few people understand it, actually as it stands, even as it stood when Darwin expressed it, and even less as we now may be able to understand it in biology.

Jacques Monod

The false view of evolution as a process of global optimizing has been applied literally by engineers who, taken in by a mistaken metaphor, have attempted to find globally optimal solutions to design problems by writing programs that model evolution by natural selection.

Richard Lewontin

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Thursday, September 27, 2007

Polycystic Liver Disease

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