Drug companies are exploiting rare mutations

Drug companies are exploiting rare mutations(bloomberg.com)

48 points by jbp 10 years ago | 5 comments

tokenadult 10 years ago |

The key idea is that genetic variants that have strong phenotypic effect through variation in just one gene are mostly rare, and genetic variants influencing most human traits of interest (heart disease risk, cancer risk, physical stature, alcoholism, IQ score, etc.) act in combination with many other gene variants, each of which alone has weak effect. This is the consistent finding of genome-wide association studies (GWASes) as those studies grow in sample size and in sophistication of the statistical analyses applied to them. Most gene variants in the human genome have nil effect on phenotype or such a weak effect that the influence of that one gene is undetectable even in GWASes with hundreds of thousands of subjects. So the word "rare" in the submitted article title (from the article description in the original article metadata) is the key word here.

These rare gene defects with strong effect on phenotype are likely to be helpful in illuminating the biological pathways involved in individuals developing those phenotypes, if the individuals are studied thoughtfully in clinical studies and especially if genetic engineering in an animal model can replicate the effect. But many of the diseases and disorders that you and I most care about will not be understood through this kind of research, because those diseases and disorders are already known to be polygenic (influenced by many genes, each of small effect) and multifactorial (subject to influence both from genes and from various environmental factors, some of which are very poorly understood). Identical (monozygotic) twins differ for many traits of interest, showing that influences other than genetic influences still make a difference in human development.

jonawesomegreen 10 years ago |

I'm super surprised that the fellow who cannot feel pain was able to make it through childhood without very serious injuries. As the article mentioned things as simple and teething would be a very different experience without pain.

masklinn 10 years ago | |

He did not (well unless you consider the threshold to serious injuries at losing a limb I guess). Looking up Steven Pete and assuming there probably aren't two 30-something pain-insensitive Steven Pete out there brings up http://www.thefactsofpainlesspeople.com/Steve.html which notes that "Visits to the Emergency Room and long hospital stays were quite frequent for my brother and I." and a number of other injuries-related notes.

They were lucky, apparently their parents (both he and his brother are pain-insensitive) were highly aware of the risks, observant and diligent, and drilled them on safety especially with respect to infections.

The article notes that Steven Pete's congenital analgesia was discovered after his parents found him "chewing on [his] tongue" which I assume is to be interpreted more or less literally (though at 4 months old hopefully without much damage)

gwern 10 years ago | |

Early in the article, it mentions he almost chewed off his tongue, which sounds pretty serious to me, and towards the end it mentions, "Pete’s left leg is permanently damaged from years of injuries he couldn’t feel, and he lives with the anxiety that he could overlook a severe illness, such as appendicitis, whose major symptom is pain."

melling 10 years ago |

This is a lot of donated information. Would it be beneficial to have 10x or 100x more people?

"Genentech is collaborating with Silicon Valley startup 23andMe, which has sold its $99 DNA spit kits to 1 million consumers who want to find out more about their health and family history—more than 80 percent have agreed to have their data used for research"