Ezra & Ross as still arguing about the definitions for eugenics and what not. Clearly there is a lot of baggage associated with the "e-word." In any case, in an email exchange with Armand Leroi about the use of the term "eugenics" to refer to selective abortions of individuals whose fitness verges upon zero (and so aren't going to have a long term impact on the gene pool anyhow) it seems clear that his own view of the term is more liberal than Ezra or mine. And when someone in John Brockman's stable talks, we should listen because these are the public intellectuals who have disproportionate impact on our understanding of scientific terms (another Brockmanite, Dawkins, was the one who introduced eugenics as one of his "Dangerous Ideas"). I suspect operationally more people would align with a broad usage of the term, though "eugenics" has too many negative associations for it to be resurrected I would bet. But in any case, as I have suggested the semantical argument is besides the point, no matter if x, y & z are instances of eugenics, x, y & z are already penetrating the domain of normalcy. As many of Ross & and Ezra's readers note part of Ross' objection surely has to do with the fact that he is opposed to abortion on principle, which is a proximate process via which selection for traits can occur. How would he feel about the screening of unfertilized gametes? One can imagine super-wealthy social conservatives going to the extent of not destroying life in such a manner. For Dune nerds you know that the Bene Tleilax perceive themselves to not be violating the injunctions of the Butlerian Jihad (which do include bans on particular genetic technologies), but they certainly violate the spirit of the law. Conversely, I assume that most pro-abortion rights liberals are not down with the creation of Aryan supermen, but genetic technology is going to be advanced enough soon that two parents who want blonde and blue-eyed children and have the genetic potentiality for such offspring can load the die. I have noted in email to friends that with the knowledge of the genetics of skin color many South Asian couples could now load the die so that their offspring would be selected from the lighter skinned range of the probability distribution (the extant variance of the South Asian genetic architecture naturally results in offspring that deviate from the expectation a lot). These are questions which I think are more interesting than the definition of eugenics.

Update: The Elf weighs in. I think she hits it about right, though this is a sprawling issue, made worse by the fact that there are disagreements about the term. The only qualification I would have is that some Lefty/progressives with a strong sympathy toward Deep Ecology and China's population policies might be the sliver of a connection that conservatives might be looking for between the past and the present (albeit, this is a very small group from what I can tell).

Related: Notes on Eugenics.

Labels: Genetics

In the comments below in regards to eugenics I made an argument that rationing is going to be inevitable in national health care systems as the information we have about the propensity (or inevitability) of diseases outruns the ability to treat those diseases. In particular, I believe that it may come to the point where though one can treat something in theory with medical technology the costs may simply be prohibitive. The argument I'm making smells a lot like Malthusianism, insofar as I believe that genomic diagnostic technologies will decrease in price in a manner that scales downward to a far greater extent then the treatments for those diagnosed probabilities for the total sample space of possibilities. But of course, we know how Malthusianism worked out when it came to the argument about population & food production, so I'm not sure about this. We (humans) have a tendency not to account for future innovation. In the near-term (less than 20 years) what do those who know about the costs of medicine think?

Labels: politics

On my other weblog I posted about research which suggests Neandertal-human cohabitation in France. A reader pointed me to the visual proof of the hybridization event.

Labels: Evolution

The latest phenotype to get the scrutiny of a genome-wide association study is multiple sclerosis: three separate reports (ok, only one of them is genome-wide) point to variation in various immune system genes as predisposing to the disease. The effects of one of the variants seems to be non-additive-- one group reports that the heterozygotes for the "causal" allele seem to actually be protected, while the homozygotes have a higher risk.

There are a number of reason why this could be the case-- linkage disequilibrium patterns and the existence of multiple predisposing alleles can lead to odd patterns of risk, even flipping the apparent effect in some cases. Another possibility, of course, is that there's some interesting biology there. More research, as they say, is needed.

Labels: Association, Genetics

Ross Douthat is concerned with the "New Eugenics." He linked to my summation of some of the data which Armand Leroi has collected on the rise of selective abortions & genetic screening. Ezra Klein isn't buying Ross' characterization of course; actually, like Ezra I think there are serious differences between the old eugenics which emerged from the biometrical school (which became quantitative genetics) and the new eugenics which is predicated on the ubiquity of genomic & fertility technology. Nevertheless, in the proximate sense, for example in our life spans, it might not make much of a difference whether the selective abortions are of heritable traits or those with would result in sharply reduced fitness anyhow (like Down Syndrome). It seems to me that to some extent the Left, which does not fear reproductive technology, is allergic to the term eugenics because of its historical resonances. I'm not going to argue over a word. But, I will offer that Richard Dawkins, no Ross Douthat, is willing to bring up the term in reference to the trends in genetics. I think that sentiments and dynamics reminiscent of the old eugenics is pretty much inevitable now that "we have the technology," it really doesn't matter what you call it.

P.S. And once we get government backed health care in the USA I'm pretty sure that the element of coercion will come into play (perhaps we'll call it "incentives for terminative preventative care" or something).

Labels: Genetics

Religious concepts promote cooperation:

Participants primed with religious concepts gave their partner an average of $4.22, compared with only $1.84 in the control group. But those who declared themselves religious before the study were no more generous than non-believers.

"The effect of the religious prime was both large and surprising, especially considering that during exit interviews the participants were unaware of having been religiously primed," says Shariff.

A second study introduced a third group, primed with words associated with civic responsibility such as "jury", contract", and "police." This group behaved almost identically to that primed with religious concepts.

You can read the full working paper for free. There were two groups. One consisted of 50 UBC students, and the second a somewhat larger and more diverse group from the Vancouver, BC, area. The basic finding was that "priming" subjects with religious terms seemed to elevate generosity during an un-iterated Ultimatum Game, where the 'rational actor' should just keep all the money. In the first sample there wasn't even a statistically significant difference between religious & irreligious students in how they reacted to the priming. The second study was more equivocal, and the authors in the discussion suggest that part of the reason that the irreligious tended to be less responsive toward religious priming was that the greater stringency of the test for 'atheism' filtered the individuals to a greater degree who were defined as non-religious, and a small number of subjects might simply even lack the implicit resonances of supernatural agents. Finally, the second study also showed that subjects could be primed toward generosity by exposing them to civic terminology.

First, the authors note the problems with their small and narrow sample sizes. Though statistically significant and powerful, the effects were derived from people from the Vancouver area, or, college students at UBC. I didn't see controlling for the fact that there is likely some correlation between ethnicity and religion in British Columbia. Specifically, a disproportionate number of secular British Columbians are likely to be Chinese origin. Second, cognition expresses and develops within a cultural context. In a society with less civic engagement and activity than Canada I would not be surprised if the effect of secular priming was trivial. Similarly, in a society that is extremely secular (Japan?) one might see far greater response to civic priming than the supernatural equivalent. Third, the authors suggest that the response of theistic and non-theistic individuals in the first group to supernatural concepts suggests an implicit association between religious concepts and altruistic behavior. I have suggested myself that the anthropomorphic bias which is a pillar of religiosity exists in many, or all, atheists. Rejection of a deity might be sincere on the explicit level, but the implicit mind might still be strongly shaped by early cultural conditioning. The secular individuals in the UBC sample were no doubt aware of the valences and power of religious beliefs and ideas, and it seems plausible that lifetime implicit associations would have been built up.

Overall, this study is good because as the researchers point out there is a lot of armchair bullshitting on this topic. I get plenty of it in the comments of my weblogs. This study shows supernatural agents can act as mediators of human action as posited by many. It also shows that secular institutions and values can trigger the same change in behavior. What does this tell us on the fundamental level? I'm not sure, after all, the typical modern human has been exposed to several thousand years of philosophical religion which has embedded within it an explicit moral/ethical dimension. Similarly, bureaucratic government and the ideologies of mass societies are "in the air," so to speak. In some "primitive" societies gods are seem as much more amoral creatures than in "advanced" cultures; they are mischievous agents who humans must placate and deceive. Additionally, they have no well developed theories of statecraft or a conception of law enforced by political fiat. It would be interesting to do this sort of study in a primitive society, though obviously the lack of literacy would cause problems with the priming the researchers used in this case.

Labels: Psychology, Religion

I did a poor job asking pubmed for the paper Razib mentioned earlier, but this surely does look interesting:

Brain pathology in pedophilic offenders: evidence of volume reduction in the right amygdala and related diencephalic structures.
Kolja Schiltz, Joachim Witzel, Georg Northoff, Kathrin Zierhut, Udo Gubka, Hermann Fellmann, Jörn Kaufmann, Claus Tempelmann, Christine Wiebking, Bernhard Bogerts

CONTEXT: Pedophilic crime causes considerable public concern, but no causative factor of pedophilia has yet been pinpointed. In the past, etiological theories postulated a major impact of the environment, but recent studies increasingly emphasize the role of neurobiological factors, as well. However, the role of alterations in brain structures that are crucial in the development of sexual behavior has not yet been systematically studied in pedophilic subjects. OBJECTIVE: To examine whether pedophilic perpetrators show structural neuronal deficits in brain regions that are critical for sexual behavior and how these deficits relate to criminological characteristics. DESIGN: Amygdalar volume and gray matter of related structures that are critical for sexual development were compared in 15 nonviolent male pedophilic perpetrators (forensic inpatients) and 15 controls using complementary morphometric analyses (voxel-based morphometry and volumetry). Psychosocial adjustment and sexual offenses were also assessed. RESULTS: Pedophilic perpetrators showed a significant decrease of right amygdalar volume, compared with healthy controls (P = .001). We observed reduced gray matter in the right amygdala, hypothalamus (bilaterally), septal regions, substantia innominata, and bed nucleus of the striae terminalis. In 8 of the 15 perpetrators, enlargement of the anterior temporal horn of the right lateral ventricle that adjoins the amygdala could be recognized by routine qualitative clinical assessment. Smaller right amygdalar volumes were correlated with the propensity to commit uniform pedophilic sexual offenses exclusively (P = .006) but not with age (P = .89). CONCLUSIONS: Pedophilic perpetrators show structural impairments of brain regions critical for sexual development. These impairments are not related to age, and their extent predicts how focused the scope of sexual offenses is on uniform pedophilic activity. Subtle defects of the right amygdala and closely related structures might be implicated in the pathogenesis of pedophilia and might possibly reflect developmental disturbances or environmental insults at critical periods

Labels: Amygdala

Razib recently mentioned a paper on a polymorphism regulating memory in Drosophila. As I often do when studies like these are published, I determined the human homologue of the gene in question (PRKG1, in this case), and checked out the plots of summary statistics available online. Sure enough, there are peaks in the significance of iHS, Tajima's D, and Fay and Wu's H in the area (all signs of recent selection), though strikingly these peaks are only evident in the Asian population. Hm.

Labels: Population genetics

Recently purchased a video iPod. I am the nerd sitting outside the coffeeshop groking brain network dynamics on my tiny screen. At least my case is stylish.

Here is a trove on that subject:
Conference on Brain Network Dynamics, 1/26/2007

That conference was in part a tribute to Walter Freeman. Here is more from him:
Poetry of Brains

Digging around more you can find several videos from the Redwood Center for Theoretical Neuroscience. For instance, Micro-circuits of Episodic Memory: Structure Matches Function in the Hippocampal System, and a debate entitled "Waves or words in cortex?" featuring Professor Freeman again.

On the mathy tip, you can download .mov's on some pretty interesting topics from the Mathematical Sciences Research Institute. If someone can point me to a converter so I can carry them around with me I would be muy grateful. I'm more interested in the ones that seem to have some relation to biology such as Frances Tong on Normalization of Western Blots.

Speaking of .movs to convert. I found an extensive discussion by Mark Ptashne on his book, A Genetic Switch. Presumably this coincided with the release of the new edition: A Genetic Switch, Lecture Series.

Who's a Nerd, Anyway?:

But the nerds she has interviewed, mostly white kids, punctiliously adhere to Standard English. They often favor Greco-Latinate words over Germanic ones ("it's my observation" instead of "I think:), a preference that lends an air of scientific detachment. They're aware they speak distinctively, and they use language as a badge of membership in their cliques. One nerd girl Bucholtz observed performed a typically nerdy feat when asked to discuss "blood" as a slang term; she replied: "B-L-O-O-D. The word is blood" evoking the format of a spelling bee. She went on, "That's the stuff which is inside of your veins," humorously using a literal definition. Nerds are not simply victims of the prevailing social codes about what's appropriate and what's cool; they actively shape their own identities and put those codes in question.

I think the researcher interviewed is a bit too obsessed with straight-jacketing nerds into a racial identity (white). I speak as a brown nerd, though I doubt I'm as socially antagonistic toward colloquial slang and conventional mores as the archetypical nerds. Rather, I think the key to nerditutde is the lower emphasis on being accepted and so assimilating the normative tardish value system (who cares if your friends make fun of you for reading? Keep at it!). Of course, many more socially aware intrinsic nerds become adept at mimicking the tardish comportment during high school, only to show their "true colors" in college when they continue to focus academically and go on to professional jobs. Any true nerdologist has to grapple with the reality that the majority of nerds might actually be "passing."

Labels: culture

Just a quick question for readers: does social networking software help out in your professional life? I'm a very tepid user of the various sites, I accept invites and so on, but it isn't something I invest a lot of time on in building a large of number of friends/contacts or fleshing out my profile. I know that some research has shown that a professional contacts are often found through your second-tier relationships, that is, not close friends but good acquaintances and what not. People who you know, but whose contacts don't overlap much with yours. So I suppose that's the point of something like linkedin. But does it really work? I've receive much better contacts through the blog, email, e-lists and so on.

(note, I am not disputing that social networking software helps your personal or social life. I know many people who've gotten action through friendster or myspace, but no one who has made professional gains via linkedin)

Labels: Blog

Most of you have probably already seen/heard about this, but check out true porn clerk stories.

Labels: Blog

A Mind for Sociability:

The amygdala, a small, almond-shaped area deep within our brains, appears to be essential in helping us read the emotions of others. Research shows that the structure is crucial for detecting fear, but scientists have also found evidence that it can help spot a wide variety of mental states...scientists noted that the amygdalas of patients with autism, which is characterized by decreased social interaction and an inability to understanding the feelings of others, have fewer nerve cells, especially in a subdivision called the lateral nucleus.
...
In humans, however, the lateral nucleus occupied a bigger fraction of the amygdala, and was larger compared to overall brain size, than in the other species, the team reports online today in the American Journal of Physical Anthropology. Although the functions of the amygdala's subunits are unclear, the lateral nucleus makes more direct connections with the brain's temporal lobe--which is involved in social behavior and the processing of emotions--than other parts of the amygdala make, the researchers note.

In Grooming, Gossip, and the Evolution of Language Robin Dunbar argued for the critical selective pressure of social groups in driving up the size and complexity of the human brain (and obviously, the emergence of language). This might explain the gradual increase in brain size over the past few million years until about 200,000 years B.P., but what about the Great Leap Forward & expansion out of Africa ~50,000 years ago? Remember, behaviorally modern humans postdated anatomically modern humans (e.g., a form of H. sapien which was gracile, high cranial vault, etc., was extant in Africa before expanding to the rest of the world) by 150,000 years. In The Dawn of Human Culture Richard Klein suggests that there was a biological change, a reorganization of the brain (Dunbar offers this idea as well). Greg has suggested that Neandertal introgression & hybrid vigor might have been at work; remember that Neandertals had the largest cranial volume of any Homo species. In The Prehistory of the Mind: The Cognitive Origins of Art, Religion and Science Steven Mithen suggests that the breakdown of separation between domain specific intelligennces (e.g., social intelligence, theory of mind, intuitive physics, folkbiology, etc.) was the critical factor in triggering the cultural revolution which lead to modernity. Mithen argues that the use of analogy to map across the various domains, and apply insights from each domain to the others, might have resulted in a massive increase in cognitive flexibility and creativity. A neurobiological implication that our species' amygdala is more "hooked in" with our "higher cognitive functions" seems to lend some credence to that viewpoint.

Update: Kambiz has more.

Labels: Evolution

When you've blogged for a while, and with some frequency, you wonder what this is all about. I don't generally get too caught up in that, there's more interesting stuff to contemplate. But, check out this from Google Analytics for the past 30 days of traffic for this website:


I've long known that most GNXP "readers" are "one off" events. I have no problem with that, if they find what they're looking for then you've done some good. That being said, I was a little shocked (and pleased, frankly) to see that over 8,000 visitors have arrived over 200 times in the past 30 days! I don't know, or care, about the details of how Google calculates this, rather, I'm interested in the gestalt sense of what's going on. Obviously the same people don't come everyday, but our unique visitor traffic has been in the 2,000-4,000 range for years, so these data together suggest that many people skip days (perhaps refreshing the site a lot on the weekend, or during one particular post where they participated in the thread?).

(click image for larger view)

Labels: Blog

Since we're talking about sex & evolution I thought I would pass on this PNAS paper, Coevolution of robustness, epistasis, and recombination favors asexual reproduction (my emphasis). I covered statistical epistasis a few years ago, and at that point I was being told that synergistic epistasis was the critical cog that kept the species a rollin' and a rockin'. But perhaps not (the paper is Open Access).

Labels: Genetics

The Economist has a story about a mutant asexual crayfish lineage. It points out how this is a good test of the sex-is-good-against-disease thesis. The basic logic is that an allele which causes asexuality has a greater short term natural increase (because it has a 100% as opposed to 50% chance of being passed to the next generation). Nevertheless, because the conventional reshuffling that occurs during sexual reproduction through the synthesis of two haploid gametes into a diploid (as well as recombination) is not operative in a the clonal lineage, they are vulnerable to fast adapting pathogens which might wipe them out. One could conceptualize the modal genetic profile of the lineage as the selective pressure exerted upon the pathogens. In the case of an asexual lineage the the pathogen has a straight shot at a stationary adaptive peak (mutation of course will introduce variation over time). In contrast, sexual lineages with their wide distribution of of genetic architectures are like moving targets, as a population of pathogens shifts toward one peak, selection within the host population reshapes the adaptive landscape (remember the power of selection is proportional to extant heritable variation, which sexual lineages have in abundance vis-a-vis clonal ones). Imagine, if you will, a rugged adaptive landscape with many peaks always bubbling and morphing, as the pathogens race up the slopes the ground underneath them shifts and gives away and soon they find themselves having to traverse a radically altered surface. In contrast, an asexual population would exhibit one sharp peak of relative stability, and its lack of genetic variation means that the surface itself is relatively rigid and stable.

Note: Some researchers have proposed that the persistence of sex in complex organisms is a function of phylogenetic constraint. That is, once the lineages flipped from asexual to sexual they couldn't flip back, even if it was adaptive. This sort of view is rather diminishes the power of selection to overcome phylogenetic hurdles. To my mind crayfish are a rather complex organism. But to those of you who know organismic biology: what is the most complex animal which can reproduce asexually? (I'm assuming it is a reptile?) It is supposed that imprinting prevents the emergence of asexuality in mammals.

Labels: Genetics

People have bugged me about the "open thread" for a while, so by popular demand, it's back. It will be to the right indefinitely, though I'll purge it of old/tardish comments regularly. Please place interesting links/sites, etc. (this includes items of interest to young straight males, *hint*, *hint*).

Labels: Blog

Self-centered cultures narrow your viewpoint:

Chinese students would immediately understand which wooden block to move - the one visible to both them and the director. Their US counterparts, however, did not always catch on.

"They would ask 'Which block?' or 'You mean the one on the right?", explains Keysar. "For me it was really stunning because all of the information is there. You don't need to ask," he adds.

While 65% of the American participants asked this type of question, only one of the 20 Chinese subjects did so, equating to just 5%.

This comes close to the classic "they did a study on that?" criticism of psychology. Of course we know that East Asians cultures emphasize a contextual perception of self and collectivist values vis-a-vis Western ones. But, it is nice to get a quantitative sense of the extent of this difference. You can read the full paper on the author's website. Here is an important point:

In fact, language can trigger a culture - bound representation of self...bicultural Chinese-born individuals tended to describe themselves in terms of their own attributes when writing in English, but to describe themselves in relation to other people when writing in Chinese.

This shouldn't surprise you if you read Geography of Thought. It seems people can be easily "trained" to change their vantage points (casting some light on the grand claims made by the author in the aforementioned book). The facultative nature of these extreme differences seems pretty obvious; especially given that extreme individualism manifest in English speaking peoples in particular, while continental Europeans tend to lay between the East Asian collectivism and Anglo-Saxon collectivism despite their far closer genetic affinity to the latter. Nevertheless, though the extremity of the differences in operation of Theory of Mind here is likely cultural, I can not be suspect that there might small, but significant, initial differences between populations. After all, Jerome Kagan has shown that personality differences exist between Asian and European infants at very young ages, as well as between blue-eyed and brown-eyed children (in both cases the former tend to be more withdrawn and inhibited than the latter). The question that comes to my mind is whether the cultural differences selected for different personality profiles, or whether there were initially difference personality profiles which resulted in different cultural outcomes. My own suspicion in the East Asian case is the former.

Labels: Psychology

A Hunk's Dental Downfall:

When males and females were about the same size, so were their teeth. But in species in which larger males evolved, tooth size increased relatively little. Thus, females ended up with larger chewing surfaces for their size than did males, the researchers report in the September issue of American Naturalist. The team concludes that teeth probably didn't grow at the same rate as body size because males can successfully compete for females only in their prime. Once teeth wear down, they become ineffective, and the animal gets weaker and more susceptible to disease or injury. But that doesn't matter to these males, as once they are too old to beat out rivals for mates, there's no need to live a long life. When it comes to how many offspring a male can father, "it seems that compared to body mass, tooth size is relatively unimportant," says Joanne Isaac, a mammalogist at James Cook University in Townsville, Australia, who was not part of the study team.

In highly polygynous species males in their prime are the fathers of a multitude. These species' males enter into a winner-take-all lottery game when it comes to reproduction. It makes sense that these males wouldn't live that long. It isn't likely that they could greatly increase the fitness of their numerous offspring through parental investment simply because there might be so many of them. Male investment in humans makes some sense in the case where a typical man may have only a few children who survive to their reproductive years. Nevertheless, there is some reproductive skew within our own species, and the extent of that skew varies from population to population and across historical epochs. The reproductive outcome for the total population may remain the same no matter if it is characterized by a equilibrium of low risk & low yield male strategies, or high risk and high yield strategies, but the dynamics within the society are likely going to be very different. I am not convinced that our current low risk & low yield strategy (i.e., monogamous pair-bonding) isn't just a metastable situation, highly susceptible to disruption.

Labels: Evolution

Kosik and colleagues used laser capture microdissection to get RNA populations from dendrites or cell bodies of cultured rat neurons. They optimized their technique so that mRNAs known to be enriched in dendrites, such as CaMKII and MAP2, showed about equal levels from soma and dendrite. They then performed multiplex PCR for several mRNAs and 187 miRNAs. The distribution of mRNAs and miRNAs is similar with a large somatic population and a gradient going out into the dendrites. Some small proportion of miRNAs have a little bit of dendritic enrichment. One point the authors are trying to get across is that there is no such thing as a 'dendritic RNA' because even the mRNAs and miRNAs that show some dendritic localization usually show just as much in the cell body.

Two nice things are that this paper validates a couple miRNA target prediction programs (Pictar and Targetscan) and that they provide a quantitative view of the miRNA copy number per cell. Both of these prediction programs suggested that miR-26a would target MAP2. This is convenient since both showed a somatodendritic distribution, meaning they hang out together even out at the farthest dendritic reaches. Inhibition of miR-26a with a synthetic oligonucleotide resulted in increases in MAP2 protein expresion, as one would expect from the classic miRNA-target relationship. As far as I am aware this brings the total of known dendrtici miRNA target pairs up to three, the other two being mir-268 and CaMKII (in drosophila) and miR-134 and LIM-Kinase. Quantification was achieved using PCR with known copy number standards. They knew how many cell bodies they captured, so they could get a copy number per cell estimate (probably a minor undershoot since even if they are awesome they probably couldn't save allllll the RNA from degradation). Anyway, they found... well I'll let them explain it:

rno-miR-124a is among the most abundant miRNAs in neurons and fell in the range of 10^4 copies per neuronal cell body. Despite its abundance, rno-miR-124a is enriched in cell bodies. rno-miR-26a and rno-miR-16 are less abundant miRNAs and fell in the range of 10^3 copies per neuronal cell body (Table 6). Because (delta)Ct of 2.61 +/- 0.39 describes the distribution of most miRNAs between the cell body and neurite, the number of copies of many miRNAs distributed along this gradient may be as low as in the hundreds of copies in the dendritic compartment. Even a one-order-of-magnitude error in this number is far below the number of synapses on the dendritic tree, and, therefore, the copy numbers of many miRNAs are likely to fall below one per synapse.

Delta Ct refers to the number of PCR cycles (i.e. doublings) it takes for the dendritic levels to reach the somatic levels. For instance, a delta Ct of 2.61 means that there are 2^2.61 (~6.1) times more somatic copies of the miRNA than there are dendritic copies.

I was particularly intrigued by this last sentence even though I have no idea what it means:

Stochasticity derived from the effects of miRNAs will contribute to the activation barrier for coherent responses, to the utilization of information provided by translational bursting, and to the flexibility needed by dendrites to sample alternative states (Kaern et al. 2005).

Guess I'll have to read Kaern et al. real quick.

Labels: dendrites, microRNA, RNA

AIDS is obviously not a genetic disease-- if one were to make a list of risk factors predisposing to HIV infection, genetics would be a pretty low-ranking member (though still present on the list, of course). Yet genetics is still a useful tool for understanding the disease, as evidenced by this paper:

Understanding why some people establish and maintain effective control of HIV-1 and others do not is a priority in the effort to develop new treatments for HIV/AIDS. Using a whole-genome association strategy we identified polymorphisms that explain nearly 15% of the variation among individuals in viral load during the asymptomatic set point period of infection. One of these is found within an endogenous retroviral element and is associated with major histocompatibility allele HLA-B*5701, while a second is located near the HLA-C gene. An additional analysis of the time to HIV disease progression implicated a third locus encoding a RNA polymerase subunit. These findings emphasize the importance of studying human genetic variation as a guide to combating infectious agents.

People trained to think about disease from a "public health" (read: short-term) standpoint might be a little appalled by the amount of money spent on a study like this-- those hundreds of thousands of dollars could very well have been spent on far more effective ways to reduce AIDS prevalence.

However, the goal here is more long-term-- understanding the variation in how humans interact with pathogens will lead to more effective drug targeting and greater understanding of immunity down the road. Genome-wide association studies also, given the fact that they are largely hypothesis-free, also provide a way to generate novel hypotheses (or confirm old ones) about disease aetiology. In this study, for example, one of the major signals lies in an endogenous retrovirus-- that is, a virus that has incorporated itself into the genome. This raises the intriguing possibility that some of our immune response is mediated by viruses that previously spliced themselves into the genome (the authors mention that antisense transcripts would be a very plausible mechanism by which that could work).

The genetics of any phenotype you can think of will eventually be mapped, and this information will be useful not necessarily for its predictive value (though in some cases that will be the case), but also for the basic understanding of the phenotype that it carries with it. This site sometimes sees speculation as to the causes of variation in sexual orientation, for example-- genetic studies (assuming they're carried out) will severely restrict the plausible "hypothesis space" on that question.

Labels: Association, Genetics