Panaceia or Hygeia

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Archive for the ‘genetics’ Category

Every disease is “genetic”. So what?

Posted by Colin Rose on December 29, 2008

Every disease is caused by some combination of nature and nurture, genetic susceptibility and the environment, especially nutrition. Fortunately, most of the common fatal diseases and those costing the most to the disease care system are mostly environmentally caused. Attempts to find a simple genetic cause for atherosclerosis, hypertension, obesity and Type 2 diabetes were and are unscientific fishing expeditions driven by the analogy that we could immunize the population against these chronic diseases of lifestyle, as we can immunize against acute infectious diseases like polio or smallpox. As this paper makes clear the four-billion year old genetic code is a highly refined, self-referential system that is unlikely ever to be completely understood.

Unfortunately, changing the environment, aka lifestyle, necessitates conquering legal addictions to junk food, tobacco and alcohol. We would much rather spend $many billions on a futile attempt to find a magic genetic bullet to obviate the destructive consequences of addiction than face the painful necessity of eliminating them. 

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Genetic diseases may be tougher to crack, new research suggests 

Last Updated: Friday, December 26, 2008 | 4:07 PM ET 

Finding a cure for many genetic diseases — including some cancers and neurodegenerative ailments — may be much more complicated than previously thought, new research indicates.

An international team’s work on alternative splicing, the process that produces 75,000 of the proteins in human cells, found that small changes in the environment near an alternative splice could produce a large change in the proteins produced.

That’s important, because mutations in DNA sequences in alternative splicing cause more than half of all genetic diseases.

If the materials used in splicing are seen as forming a long sentence, then the individual parts can be considered words, said Tim Nilsen, director of the Case Western Reserve University School of Medicine’s Center for RNA Molecular Biology in Cleveland.

“Adding or deleting one word,” he said “can radically change the meaning of the sentence.”

Biologists believe that rules hidden in the DNA code control alternative splicing, so once the code is broken, cures can be found for genetic diseases.

But the finding by Nilsen’s team on the importance of the environment means the code is much more complicated than thought. That will likely delay that progress of scientists who hope to amend the code to cure genetic diseases, said Joseph Nadeau, chair of the medical school’s genetics department.

“It’s context, not [genetic] code, that’s important,” he said.

The study, Dynamic regulation of alternative splicing by silencers that modulate 5′ splice site competition, was published in the Dec. 24 issue of Cell.

Nilsen led a team from three U.S. institutions — Case Western, Columbia University and the Memorial Sloan-Kettering Cancer Institute — and the Max Planck Institute for Biophysical Chemistry in Germany.

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The Junk Food Gene

Posted by Colin Rose on December 10, 2008

After $many billions spent on looking for genetic causes of common diseases like obesity we now have the answer in the latest NEJM that was obvious without spending all that money. The most common SNP (single nucleotide polymorphism) associated with obesity tends to influence people to eat high-fat, energy dense food, commonly known as junk food. We already knew that obesity was not caused by “slow metabolism”. So, no junk food, no junk food addiction, no obesity. Junk food addiction is like any addiction. If an alcoholic has a bottle in the house s/he will drink it. So don’t buy junk food and you won’t eat it.

To quote from the Discussion in the paper:

“This study indicates that there is no defect in the “output” side of energy balance, which constitutes energy expenditure…Our study tested satiety by directly measuring food intake from a test meal after ingestion of one of three preloads, and the results show a robust effect of genotype on energy intake but not on the weight of food ingested. This increase in energy intake was independent of body weight. Thus, the children carrying the A allele ingested more energy-dense foods than did the children who were not carrying the A allele, indicating a preference for energy-dense foods….In conclusion, variation within the FTO locus appears to confer a risk of obesity through increased energy intake, suggesting that moderate and controlled restriction of energy intake may prevent FTO genotype–associated obesity.”

nejm-fto-obesity-abs

Another Ice Cream Cone

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