Gene Sequencing growing faster than Moore's Law

Gene Sequencing growing faster than Moore's Law:

Wow.

iPOP (integrative personal omics profile) – tracking proteins, metabolites, metabolism, microRNAs, cytokines, antibodies, and gene transcripts in one person

Michael Snyder tracks his health status with iPOP and finds a virus causing his Type 2 Diabetes (T2DM)?

Snyder had a cold at the first blood draw, which allowed the researchers to track how a rhinovirus infection alters the human body in perhaps more detail than ever before. The initial sequencing of his genome had also showed that he had an increased risk for type 2 diabetes, but he initially paid that little heed because he did not know anyone in his family who had had the disease and he himself was not overweight. Still he and his team decided to closely monitor biomarkers associated with the diabetes, including insulin and glucose pathways. The scientist later became infected with respiratory syncytial virus, and his group saw that a sharp rise in glucose levels followed almost immediately. "We weren't expecting that," Snyder says. "I went to get a very fancy glucose metabolism test at Stanford and the woman looked at me and said, 'There's no way you have diabetes.' I said, 'I know that's true, but my genome says something funny here.' "

So much for "These people eat too much."

Topol writes in an e-mail, "this type of 'pan-ar-omic' study of individuals is now not only feasible but in select individuals with medical conditions, particularly useful clinically."

We'll have to wait until this will be used more often in research, and then it will take some considerable time, but it will reach clinical use some time, maybe in the next decade.

Read it all.

[Update] Here's another blog post about this.

"It’s Not so Rare to Have a Rare Disease"

Spittoon – It’s Not so Rare to Have a Rare Disease

When we think about diseases we often describe them as either common or rare. Common conditions — like heart disease and obesity — are complex in nature, meaning that they are influenced by both genetics and environment. Conversely, most rare diseases are strongly influenced by genetics and less so by environment. We hear a lot about common conditions because so many people have them and in contrast relatively little about rare diseases. But how rare is rare?

In the United States, a disease is defined as “rare” if it affects fewer than 200,000 individuals, or roughly one in 1500. Rare diseases are often poorly understood, with symptoms that can be difficult to diagnose, and can be life-threatening. Around 6,800 rare diseases have been identified and the large majority of them — up to 80% — are thought to have a genetic origin. Most rare diseases can’t be cured and many lack effective treatments because research on rare conditions is often hampered by a scarcity of study participants and poor funding.

If you add up all the rare diseases it turns out that about 30 million Americans suffer from a rare disease. That’s nearly 10% of the population — suddenly rare is not so rare! …

Well, they sell genetic tests, so they have toot their horn. But still: 10% have a "rare" disease. Wow.

One cause, different effects

If you have two faulty copies of this gene, your brain won't be normal, but what goes wrong varies widely amongst different people. Although the 9 cases had some features in common, such as microcephaly (small head and brain), in other respects they differed greatly.

As the authors put it, mutations in WDR62 cause
a wide spectrum of severe cerebral cortical malformations including microcephaly, pachygyria with cortical thickening as well as hypoplasia of the corpus callosum. Some patients... had evidence of additional abnormalities including lissencephaly, schizencephaly, polymicrogyria and, in one instance, cerebellar hypoplasia, all traits traditionally regarded as distinct entities.

These are distinct entities, in the sense that you can have any one of them, without having the others. And they are different brain changes. What the authors mean is that everyone assumed that, because they're different, they must have different genetic causes. They've just shown that this is wrong.

So what is WDR62 "for"? Experiments in mice showed it to be involved in the migration of new neurons from their origin to their final location in the brain. So it's "for" correct neuronal placement, although how it works remains unclear.

WDR62 ought to remind us that there's a long and winding road from gene to phenotype, and that the same gene can, when mutated, cause very different symptoms. This is especially interesting in the light of recent evidence showing that the same mutations can cause a range of behavioural disorders from autism to ADHD to schizophrenia.

(via)

It's the environment, stupid!

Critics, on the other hand, have argued all along that both twin studies and family studies are unable to disentangle the potential roles of genes and environment. They have pointed out for decades that the validity of equal environment assumption (EEA) of the twin method is not supported by the evidence, and that the much more similar environments experienced by reared-together monozygotic (MZ) versus reared-together dizygotic (DZ) twin pairs confound the results of the twin method. Therefore, both family studies and twin studies prove nothing about genetics and their results can be completely explained by non-genetic factors. Most behavioral geneticists agree with this assessment as it relates to family studies, but continue to maintain that twin studies provide conclusive evidence that genes play an important role. Critics have also pointed to the massive methodological problems and untenable assumptions found in psychological and psychiatric adoption studies, as well as the major problems and environmental confounds in studies of purportedly reared-apart twins

And:

In study after study, applying GWAs to every common (non-infectious) physical disease and mental disorder, the results have been remarkably consistent: only genes with very minor effects have been uncovered (summarised in Manolio et al 2009; Dermitzakis and Clark 2009). In other words, the genetic variation confidently expected by medical geneticists to explain common diseases, cannot be found.

There are, nevertheless, certain exceptions to this blanket statement. One group are the single gene, mostly rare, genetic disorders whose discovery predated GWA studies2. These include cystic fibrosis, sickle cell anaemia and Huntington’s disease. … With these exceptions duly noted, however, we can reiterate that according to the best available data, genetic predispositions (i.e. causes) have a negligible role in heart disease, cancer, stroke, autoimmune diseases, obesity, autism, Parkinson’s disease, depression, schizophrenia and many other common mental and physical illnesses that are the major killers in Western countries.
…
This dearth of disease-causing genes is without question a scientific discovery of tremendous significance. It is comparable in stature to the discovery of vaccination, of antibiotics, or of the nature of infectious diseases, because it tells us that most disease, most of the time, is essentially environmental in origin.

Firstly, in my view, common diseases can not have its origin in genetic problems. And secondly, who says that common diseases (chronic, with presumably gradual onset and/or gradual build-up, like e.g. type 2 diabetes) can't have a infectious origin? I think nutrition is far more likley to be the culprit, but hey.

In a rare public sign of the struggle to come to terms with this genetically impoverished world-view, the authors of a brief review in Science magazine, Andrew Clark of Cornell University and Emmanouil Dermitzakis of the University of Geneva Medical School, Switzerland have been alone in stating the case even partly straightforwardly. According to them, the GWA studies tell us that “the magnitude of genetic effects is uniformly very small” and therefore “common variants provide little help in predicting risk” (Dermitzakis and Clark 2009). Consequently, the likelihood that personalised genomics will ever predict the occurrence of common diseases is “bleak”. This aim, they believe, will have to be abandoned altogether.

The first conclusion to be drawn from these quotes is that such directness implies that if the GWA findings are not finding their way to the front page the reason is not ambiguity in the results themselves. From a scientific perspective the GWA results, though negative, are robust and clear.

Most human geneticists view the GWA results somewhat differently, however. An invited workshop, convened by Collins and others, discussed the then-accumulating results in February 2009. The most visible outcome of this workshop was a lengthy review published in Nature and titled: “Finding the Missing Heritability of Complex Diseases.” (Manolio et al. 2009).

For a review paper that does not lay out any new concepts or directions, 27 senior scientists as coauthors might be considered overkill. “Finding the Missing Heritability”, however, should be understood not so much as a scientific contribution but as an effort to conceal the gaping hole in the science of medical genetics.

In their Science article, which was published almost simultaneously, Dermitzakis and Clark paused only briefly to consider whether so many genes could have been overlooked. Apparently, they thought it an unlikely possibility. Manolio et al., however, frame this as the central issue. According to them, since heritability measurements suggest that genes for disease must exist, they must be hiding under some as-yet-unturned genetic rock. They list several possible hiding places: there may be very many genes with exceedingly small effects; genes for disease may be highly represented by rare variants with large effects; disease genes may have complex genetic architectures; or they may exist as gene Copy Number Variants (CNVs). Since Manolio et al. presented their list, the scientific literature has seen further suggestions for where disease genes might be hiding. These include in mitochondrial DNA, epigenetics and in statistical anomalies (e.g. Eichler et al. 2010; Petronis 2010).

It is sad to see scientists working in the field genetics have so little grasp of evolution that they fail to see the evolutionary interdependence of genes and environment...