Research shows hope for personalized genome sequencing

July 12, 2015 by Sheena Faherty, The Philadelphia Inquirer
A depiction of the double helical structure of DNA. Its four coding units (A, T, C, G) are color-coded in pink, orange, purple and yellow. Credit: NHGRI

Imagine if you could carry a credit card-size record of all the 3 billion A's, T's C's, and G's that make up the alphabet soup of your genome. A simple swipe of the card could inform your physician right away if a drug being considered will help you - or even hurt you.

This is the kind of promise behind President Barack Obama's $215 million initiative to develop personalized medicine.

"We've arrived at the point where this could happen, and is going to happen," Francis Collins, director of the National Institutes of Health, said at a recent biotechnology conference in Philadelphia.

A newly published study by researchers at the University of Pennsylvania is another step on the path.

The study, which appears this month in the journal Cell, came from a curious case regarding a class of anti-diabetes drugs known as thiazolidinediones, or TZDs. TZDs are highly effective - in some people. But for 20 percent to 30 percent of patients, they are useless and can even cause serious side effects.

The Penn team had a hunch that the variation could have something to do with small differences in the regions of the that control whether a gene will be switched off or on, much like a . These areas, called regulatory regions, work by lighting up genes when a molecule known as a nuclear receptor attaches to DNA.

Many drugs on the market, such as TZDs, work by binding to , which regulate whether genes are turned on. The Penn researchers found that one change in the sequence of base pairs - adenine, thymine, cytosine and guanine, those A's, T's, C's and G's - in the light switch regions of the genome may ultimately predict how those drugs will affect a particular patient.

"Every drug has a risk of some sort," said Mitchell Lazar, professor of medicine and genetics at Penn's Perelman School of Medicine and senior author on the study. Figuring out how those risks are related to a person's genetic code is "one of the principles of personalized medicine."

"The cost of determining a person's genome is coming down to the point where it's widely predicted that in five to 10 years, every person will be able to have their genome sequenced," Lazar said. "Epidemiologists and statisticians will be able to correlate individual difference(s) in the genome and ask, 'Was the drug effective?' "

Finding the mutations that matter is the hardest part, said Tim Reddy, assistant professor of biostatistics and bioinformatics at Duke University, who was not involved in the Penn study. However, he said, projects like this, which identify the genetic predictors of people who respond to medications vs. people who don't, are the first steps toward making a reality.

And, Reddy said, like any good study, "this opens up a lot more questions and a lot more opportunities. Nuclear receptors are the targets of countless drugs for other diseases. I'm really excited to see how the principles that were revealed here can be generalized for other drugs that target" these molecules.

Explore further: Genetic variation determines response to anti-diabetic drug

Journal reference: Cell search and more info website


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1 / 5 (1) Jul 13, 2015
Re: " change in the sequence of base pairs..."

See: Modeling Recent Human Evolution in Mice by Expression of a Selected EDAR Variant

Excerpt: "...we used homologous recombination in embryonic stem cells to introduce the T1326C point mutation into the endogenous murine Edar locus resulting in a V370A substitution in the encoded protein (Figures 2B and S6)."

The "mutation" was linked from a single amino acid substitution to cell type differentiation of cells in similar tissues of mice and a modern human population.
5 / 5 (1) Jul 13, 2015
Keep in mind JVK is a young earth creationist.
3.7 / 5 (3) Jul 13, 2015
I don't get what point JVK is trying to make in any case...
not rated yet Jul 13, 2015
I heard "23andMe" doesn't give you an exact A,T,C,G read out of your genome, they just give you a brief summary. Does anybody know if this is true?
1 / 5 (1) Jul 13, 2015
Clinically Actionable Genotypes Among 10,000 Patients With Preemptive Pharmacogenomic Testing http://www.medsca...24253661

3 minute video of what is true about RNA-mediated cell type differentiation:
1 / 5 (1) Jul 14, 2015
Excerpt: Despite the high heritability of depression and a clear genetic contribution to the disease, the identification of genetic risk factors for depression has been very difficult. The first published candidate to reach genome-wide significance in depression was SLC6A15, a neuronal amino acid transporter. With a reported 1,42 fold increased risk of suffering from depression associated with a single nucleotide polymorphism (SNP) in a regulatory region of SLC6A15, the polymorphism was also found to affect hippocampal morphology, integrity, and hippocampus-dependent memory.

My comment: The misplaced focus on genes has skewed the entirety of what might otherwise have been rapid progress towards linking RNA-mediated amino acid substitutions and RNA-mediated gene duplication from nutritional epigenetics to pharmacogenomics in the context of chromosomal rearrangements, pathology, and healthy longevity.
1 / 5 (1) Jul 14, 2015
I don't get what point JVK is trying to make in any case...

Many others are also biologically uninformed because they have been taught to believe in ridiculous theories.
5 / 5 (1) Jul 14, 2015
I don't get what point JVK is trying to make in any case...

Many others are also biologically uninformed because they have been taught to believe in ridiculous theories.

And idiots like JVK are young earth creationists.
1 / 5 (1) Jul 14, 2015
I linked to an article and a video representation (see above) of what is currently known about how nutrient-dependent metabolic networks are linked to cell type differentiation in all genera, which links RNA-mediated gene duplication and RNA-mediated amino acid substitutions to everything currently known about precision medicine.

When I learned about the network of hospitals run by 7th Day Adventists (young earth creationists) -- I was surprised.

When I learned more about their nutritional link to precision medicine, I was not surprised because I had already detailed an atoms to ecosystems model of top-down creation of amino acids linked to amino acid substitutions. The fixed substitutions differentiate all cell types of all individuals of all genera.

Minimally, that fact should inspire others to examine precision medicine in the light of Darwin's 'conditions of life' which force intelligent medical practitioners to ignore neo-Darwinian theories.
1 / 5 (1) Jul 14, 2015
A factor required for long term immunity identified

Excerpt: "Plasma cells were created when the immune system was exposed to pathogens such as viruses or bacteria."

My comment: Did they create themselves to prevent virus-driven entropic elasticity from leading to genomic entropy? If not, these differentiated cell types probably arose in the context of the light induced de novo creation of amino acids and the need for the anti-entropic epigenetic effects of nutrients-dependent microRNAs to facilitate the repair of virus-driven damage to the organized genomes of all living genera via RNA-mediated gene duplication and RNA-mediated amino acid substitutions that link the epigenetic landscape to the physical landscape of DNA in all genera via fixation of the amino acid substitutions in the context of the physiology of reproduction.

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