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May 1, 2019

The Insight Show Notes — Season 2, Episode 25: The $1,000 Genome

Filed under: Genetics,Medicine,Podcast — Razib Khan @ 2:56 pm

The Insight Show Notes — Season 2, Episode 25: The $1,000 Genome

Citation: Rodrigo Martinez
If you haven’t, please fill out The Insight listener survey.

This week on The Insight (Apple Podcasts, Spotify, Stitcher and Google Podcasts) Rodrigo Martinez of Veritas Genetics talks about the $1,000 genome. Though the reality is we’re well beyond the $1,000 genome, which Rodrigo unpacks in detail.

Rodrigo has been at the forefront of reimagining what genomics can do. Those more interested in his ideas should see his blog post, Next in the Genomics Revolution: The Era of the “Social Genome”.

We discussed the difference between genotyping vs. sequencing, what clinical grade means, and what Veritas’ place in the ecosystem is.

J. Craig Venter

Rodrigo also tells us how a chance encounter in Mexico with J. Craig Venter in the late 1990s resulted in his interesting career path within the nascent field of genomics. One of the major themes of the podcast has been how we’ve observed genomics transform in the last generation, from blue-sky science that cost billions of dollars, to commodity data generation, and finally into the phase of value-add interpretation.

While some researchers have focused on generating the genetic data, much of Rodrigo’s focus has interpretation..been how that data is stored and represented: The Geography of the Genome. And of course, we talked about the famous chart produced by the NIH, which illustrates the cheapening of genomic data.

He talks about how the graph of “cost per genome” doesn’t explain why adoption has exploded in the last few years, rather than earlier.

The decline in genomic costs

There was an extensive discussion about how sequencing, in particular, is going to add more value than the genotyping platforms that are introducing the public to genomics. Basically, genotyping platforms looking for variation that we know exists. Sequencing is the total information of the ACGT read, therefore it allows you to discover things you didn’t even know existed!

Rodrigo envisages genomics moving from the “read” era to the “read/write” era, and finally to the “social” era. Clearly, the genome itself is not the “killer app,” but we don’t know what it will be. We talk about how interpretation and support services are going to be the primary sectors where most of the activity in genomics is going to occur, as raw sequencing becomes a commodity service.

Some of those services are going to be clearly medical. For example, drug-gene interactions. But the key insight is we don’t know the shape of the most likely use cases because information technology is so difficult to predict!

Though internal projections at Veritas indicate that they will have sequenced 1 million individuals by 2021.

Two comments in Genome Biology from 2013 and 2018:


The Insight Show Notes — Season 2, Episode 25: The $1,000 Genome was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

March 6, 2019

The Insight Show Notes — Season 2, Episode 17: Polygenic risk scores and diversity

Filed under: Genetics,Medicine,Podcast,science — Razib Khan @ 4:55 pm

The Insight Show Notes — Season 2, Episode 17: Polygenic risk scores and diversity

The risk for coronary heart disease

This week on The Insight (Apple Podcasts, Stitcher and Google Podcasts) we discuss “polygenic risk scores” (PRS) and genetic diversity with Dr. Alicia Martin. She is a researcher in the Analytical and Translational Genetics Unit at the Broad Institute of MIT and Harvard in Cambridge, MA.

Citation: Martin, Alicia R., et al. bioRxiv(2019): 441261.

We talked first about the general idea of “polygenic risk scores.” Based on centuries-old techniques of statistical prediction of an outcome (a “risk”) from numerous variables (which include various genes), the age of genomics has allowed for there to be enough data that individual genomes could be analyzed to produce results of utility. But as noted in recent work, the prediction varies by population. The accuracy is far higher in Europeans than in non-European populations, strongly correlated with phylogenetic distance.

One of the major reasons for this difference is the evolutionary history of our species. The “out of Africa” migration meant that Africans and non-Africans split first. Then Europeans from Asians.

When researchers do studies on Europeans, they “discover” variation in that population, and miss out on variation that is unique to other groups. This reduces the power of the predictions as a function of evolutionary divergence.

We discuss the various reasons for the low diversity in modern medical genomics. One reason is that European nations have taken the lead in consortiums. This means that they have a headstart and since genetic studies are easier in large numbers of homogeneous groups due to “stratification,” researchers kept studying the same populations over and over again.

This leads to accumulating differences in how well the technology is suited to different populations. For example, patterns in the genome known as “linkage disequilibrium,” the association of alleles across genes, is far more well known for Europeans. And these patterns are essential in maximizing the power of a given PRS.

We discussed Martin’s paper from 2017, Human Demographic History Impacts Genetic Risk Prediction across Diverse Populations, which pioneered the systematic exploration of this topic. And, we talked about the path forward, and how we can solve this problem.


The Insight Show Notes — Season 2, Episode 17: Polygenic risk scores and diversity was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

March 5, 2019

The dearth of diversity in genomics

Filed under: Diversity,Genetics,GWAS,Medicine — Razib Khan @ 11:24 pm
Citation: Martin, Alicia R., et al. bioRxiv(2019): 441261.

One of the curious things about genomics is the field has exploded in the 21st century so fast, with such explosive growth and increase in power, that it is hard to keep up if you blink. The first human genome cost $3,000,000,000. Now human genomes can be had for $1,000 or less. Whereas thirty years ago geneticists were debating whether you could even map the human genome, today we have hundreds of thousands of whole-genome sequences.

But some things don’t change as much as you might think. The chart at the top of this post illustrates the proportion of various ethnicities in “genome-wide association” (GWAS) studies over the past twelve years. The logic of GWAS studies is straightforward: you are searching within the genome for genetic variation that explains variation within the population. You are looking for genes that cause diseases and traits.

The chart to the left illustrates the heritability, proportion of variation which is genetic, for a range of traits. Many of these, such as obesity, heart attack, and schizophrenia, are obviously extremely relevant in a medical context. It would be best to understand the genetic basis of these diseases within the population and in the individual.

Therefore, in an ideal world, you could look at the specific genes you carry and construct a “polygenic risk score” (PRS) which predicts your lifetime probability of developing the disease in relation to the broader population. But we do not live in an ideal world.

Because most GWAS are performed in European populations, PRS values for individuals not of European ancestry are far less accurate. This phenomenon is caused by several factors. One of the major ones is that each population has genetic variations that cause diseases special and unique to a given population (“private alleles” in the jargon). Studies which use only Europeans cannot detect unique variation in non-European populations by definition. Those variants are not found in Europeans! Additionally, sometimes genetic variants even give different risks in Europeans than non-Europeans because of interactions of genes. The predictions in one population do not transfer to another.

The brains of schizophrenics are different in neuroimaging

One prediction that one could have made, and one that I did, is that the incredible cheapness of modern genomic technology would mean that people of diverse ethnicities would be included in studies over time. We wouldn’t need to do anything special, the magic of technology would solve the problem for us.

But instead, we’ve seen a process of the “rich getting richer.” European nations have robust healthcare infrastructures geared toward collecting the information needed for GWAS. Additionally, there are statistical reasons that GWAS are more powerful for homogeneous populations…as Europeans have the larger sample sizes, to begin with, many researchers continue to stay with the population with larger sample sizes!

What’s the path going forward? First, researchers are now proactively going and reanalyzing populations within datasets in the Western world with large numbers of people of non-European ancestry. Previously to obtain homogeneous datasets as noted above these individuals would be discarded from the analysis. Second, there are now proactive efforts to obtain diversity from regions outside of Europe. The African Genome Variation Project is one of these cases. Finally, private consumer genomic firms are now assembling databases of quite a large size, and a substantial number of their customers are non-European.

The past has taught us that we can’t be complacent, and simply expect the “laws of genomics” to solve the issues in relation to genomic diversity. Rather, researchers and the public have to proactively address these issues, so as to allow all of us to make the best decisions within our own lives in terms of what our genes bring to the table.

Interested in learning where your ancestors came from? Check out Regional Ancestry by Insitome to discover various regional migration stories and more!


The dearth of diversity in genomics was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

November 12, 2013

Vaccination, and social information networks

Filed under: Medicine,public health,Vaccination — Razib Khan @ 1:34 am

Preventable

If you have not read Julia Ioffe’s story about getting whooping cough at the age of 31 (also see follow up), you might want to. Here’s some further context, Vaccine Refusals Fueled California’s Whooping Cough Epidemic. This topic has been covered and dissected in great detail by many writers and scientists, so I won’t repeat what you already know in regards to herd immunity. There’s no point in preaching to the choir.


Rather, I want to offer a personal perspective. Over the past few years I’ve become much more aware of cultural streams in public health, and the public’s reaction to that health advice, because I have become a father. More specifically, when my wife was pregnant with my daughter, and after she was born, we encountered major pressure from peer networks to not vaccinate. In the social circles in which we were embedded, “progressive,” “crunchy,” and “alternative,” vaccinating one’s child was the heterodox decision. It was rather obvious to us that one of the major reasons that many people do not vaccinate their children is that many of their friends, and vocal people whom they trust, do not vaccinate their children. We were able to resist and rebuff any peer pressure rather easily because we have a much stronger scientific background than most Americans, but it isn’t hard to imagine being ignorant and trusting those in whom you normally put your trust.

In some ways I am not totally unsympathetic to the skepticism that some in the public have toward the medical establishment. Modern scientific medicine is a genuine miracle, but most of its gains arguably occurred in the first half of the 20th century through public health campaigns, vaccination and antiobiotics. Though the decline in heart disease is a major result which we should celebrate, it is arguably less significant than the sharp reduction in deaths of the young due to numerous infections (heart disease tends to effect the old). Additionally, diseases such as cancer are subject to the problem of what Jim Manzi terms “high causal density”. Cancers, like many diseases of late life, can have many triggers and factors impacting their likelihood, so solving the problem at the root may not be so simple. In reaction to this complexity and uncertainty I do believe that on occasion the medical profession and the public health establishment have unduly emphasized their certainty.

Like the reality that the variegated public health concerns we have today, such as type 2 diabetes and cancer, are probably better problems than endemic smallpox, tuberculosis, or scarlet fever, the downsides of having a medical establishment which on occasion oversteps the bounds of its reasonable confidence are overridden by the upsides. We have empirical evidence of this, because there are nations without medical establishments, and they are not flourishing. But that does not change the reality that a population shielded from the brutal knife of infectious disease and plague is somewhat befuddled by the mysteries of the slow and subtle ailments which are the afflictions of modernity.

One response is the liberal individualist one. Though we may bemoan Steve Jobs’ experimentation with alternative therapies for his cancer, it was his individual choice. It gets more complicated what you have children, who are under the control of their parents. Again, I’m not going to go over the controversies over groups like Christian Scientists, whose children have died due to withholding medical treatment. The cultural consensus seems to be that parents have a right to impose all sorts of crazy beliefs and practices upon their children, but not those which may result in death. Then you move to the issue that when it comes to vaccination one can’t seal off individual choice from consequences to the public. It seems entirely likely that for the next decade we may be seeing a conflagration of preventable diseases among certain segments of the American demographic, and those who they live among, because of cultural fashion. The collective choices of parents opting out from vaccination is subject to negative feedback dynamics. Early dissenters can “free-ride” on herd immunity, and indulge their quackery, but beyond a particular threshold disease and death will come back to the fore. But human beliefs are often rather well insulated against falsification for a great deal of time. The AIDS denialst community is a testament to this phenomenon; it persists despite mysteriously (to them) high mortality rates among its most vocal proponents.

So is there a solution? Conscience is a value which Americans pride, even unto death. I do not see the powers that be intervening in these cases. Rather, this groundswell of denialism must be countered by public opprobrium, and yes, shaming. Peer pressure kills, but it can also save lives. As a matter of safety people with small children should investigate rates of vaccination in their community (young infants are not vaccinated, and so are particularly vulnerable to infections which are dampened by herd immunity). They should move when a dangerous critical mass is present. If people ask, those who leave should explain their rationale. Actions can speak louder than words. Where Authorité falls on deaf ears, the judgment of the populace might be heeded.

The post Vaccination, and social information networks appeared first on Gene Expression.

October 29, 2012

Doctors are apparently gods, get used to it

Filed under: Genetics,Genomics,Medicine — Razib Khan @ 8:24 am

Here’s a caption from a Time article, What Your Doctor Isn’t Telling You About Your DNA:

Nice to know that two physicians in Philadelphia not only have medical degrees, but specialize in mind-reading the parents of this nation! Above the caption is a photo of  the two concerned and worried looking professionals in question. Let me quote the first two paragraphs of the article:

The test results were crystal clear, and still the doctors didn’t know what to do. A sick baby whose genome was analyzed at the Children’s Hospital of Philadelphia turned out to possess a genetic mutation that indicated dementia would likely take root around age 40. But that lab result was completely unrelated to the reason the baby’s DNA was being tested, leaving the doctors to debate: Should they share the bad news?

When it comes to scanning DNA or sequencing the genome — reading the entire genetic code — what to do with unanticipated results is one of the thorniest issues confronting the medical community. Many conflicted discussions followed the dementia discovery at the Children’s Hospital of Philadelphia (CHOP) before a decision was reached: the parents would not ...

April 16, 2012

None dare call it eugenics!

Filed under: Genetics,Human Genetics,Medicine — Razib Khan @ 8:37 pm

Well, almost no one:

“The unspoken central reason for the societal taboo and the penal ban on incest is the possibility of hereditary defects — a factor that Strasbourg only hinted at. But the intention behind the eugenic argument is one that is indefensible, and not just in Germany with its terrible Nazi past: The increased risk of hereditary defects does not justify a legal ban. Otherwise you would have to legally ban other risk groups, like women over 40 or people with genetic diseases, from having children. Does anyone truly want to prevent predictable disabilities using penal measures and thus deny disabled children the right to life in 2012? That’s absurd. And yet such fears of genetic damage are precisely what shape the punishibility of sexual intercourse between siblings.”


There are a set of arguments against near relation incest which strike me as generally ad hoc. And there’s social science to back that up. Incest is reflexively disgusting to most people (depending on how it is categorized). But disgust alone is not a sufficient grounds for banning a practice in educated circles today, so people create rationales after the fact. ...

April 8, 2012

Doctors and life expectacy

Filed under: Medicine — Razib Khan @ 4:18 pm

A friend pointed me to the following infographic on the concentration of doctors per county. The orange represents “very high need,” and dark blue “very low need.”

Now let’s compare it to life expectancy by county:

February 13, 2012

American medicine & American red-tape

Filed under: Health,Human Genetics,Human Genomics,Medicine — Razib Khan @ 6:08 pm

I just attended a presentation where a researcher outlined how epigenomics could help patients with various grave illnesses. Normally I don’t focus on human medical genetics too much because it always depresses me. I don’t understand how medical geneticists don’t start wondering what hidden disease everyone around them has. In any case the researcher outlined how epigenomic information allowed for better treatment, so as to extend the lives of patients. All well and good. But then one individual in the audience began asking pointed questions as to the medical ethics of the enterprise, and whether the researcher had cleared some legally sanctioned hurdles. More specifically, there was a question whether exploring someone’s epigenomic profile might expose private information of their relatives! (because relatives share epigenomic and genomic profiles to some extent)

Frankly I began to get enraged at this point. People are suffering from terminal illnesses, and considerations of the genetic privacy of their near relatives are looming large? Seriously? The reality is that manifestation of a disease itself gives one information about the risks of their relatives. In any case, the researcher admitted that further progress in this area is probably going to be due to the investments of wealthy individuals (e.g., people like Steve Jobs who have illnesses) as well as outside of the United States. You’re #1 America!

January 1, 2012

“Doctors don’t cure nothing”

Filed under: Causation,Correlation,Culture,False Positives,Medicine,science — Razib Khan @ 2:00 pm

NSFW


As I observed before, modern medicine is subject to some of the same statistical issues as social science in its tendency to put unwarranted spotlight on preferred false positive results. Trials and Errors – Why Science Is Failing Us:

This doesn’t mean that nothing can be known or that every causal story is equally problematic. Some explanations clearly work better than others, which is why, thanks largely to improvements in public health, the average lifespan in the developed world continues to increase. (According to the Centers for Disease Control and Prevention, things like clean water and improved sanitation—and not necessarily advances in medical technology—accounted for at least 25 of the more than 30 years added to the lifespan of Americans during the 20th century.) Although our reliance on statistical correlations has strict constraints—which limit modern research—those correlations have still managed to identify many essential risk factors, such as smoking and bad diets.


I need to look at the difference between mortality and morbidity here. The two are clearly related, but if modern medicine has decreased morbidity, then it is still worthwhile to a greater extent than simple life expectancy calculations might indicate. But the reality is that the more and more I look at modern medicine the more worried I get that the age old heuristics and biases which allowed medicine to flourish as a form of counterproductive psychotherapy up until the early 20th century are now coming back to the fore. The issue here is less the profession of medicine, as the incentives and impulses which drive the need for a “cure” from the demand side.

All this brings to mind a passage from the book Religion Explained:

E. E. Evans-Pritchard is famous for his classic account of the religious notions and beliefs of the Zande people of Sudan…one day the roof of a mud house collapses in the village…People promptly explain the incident in terms of witchardcraft…Evans-Pritchard points out to this interlocutors that termintes had undermined the mud house and there was nothing particularly mysterious in its collapse. But people are not interested in this aspect of the situation. As they point out…they know perfectly that termites gnaw at the pillars of mud houses and that decrepit structures are bound to cave in at some point. What they want to find out is why the roof collapsed at the precise time when so-and-so was sitting undernearth it rather than before or after that. This is where witchcraft provides a good explanation.

With all due respect to modern scientifically trained physicians, but the demands that their patients are now making upon them in terms of curing diseases whose causal roots are less than clear are transforming them into latter-day shamans. As it was, it will be?

December 30, 2011

Eggs: quantity and quality

Filed under: Fertility,Medicine — Razib Khan @ 3:05 am

In my post below on selection for the “better” zygote Michelle observes that “This would be relatively easy for the father, not so much for the mother.” I took her to mean either of two things,

1) Extraction of eggs is a major surgical affair. Extraction of sperm is not.

2) Males generally have many more sperm to contribute than females.

The latter issue made me go look for data on human females, by age. The paper A systematic review of tests predicting ovarian reserve and IVF outcome had what I was looking for. First, let’s review the cumulative distribution of fertility curves for women:


The way I read the figure 50% of women are sterile at 41. 50% begin their fertility drop at 31. Note that a small, but significant, minority of women are already sterile by age 35. People talk about fertility curves, but less weight is given to the fact that the curve varies in terms of its chronology!

Second, let’s look at the number and quality of ovarian follicles over time (they correspond to number of incipient eggs):

This figure is not easy to read. But you can see that at age 20 there are ~100,000 follicles. That number seems to drop by a little less than half by 30, and is at 20,000 by 40. But by this point 25 percent are of “poor quality.”

December 17, 2011

Promiscuity and vaginal bacterial diversity

It’s a fun fact that there are an order of magnitude more bacterial cells in your body than your own cells. Not only that, it’s well known that we wouldn’t flourish, let alone survive, without our gut “flora,” which digest material which would otherwise pass through out system. Not only are microbes good for us, but they’re also bad for us. The evolutionary flexibility of microbial pathogens is one of the major arguments for why sex exists among multiceullar species: it allows them to adapt to rapidly fluctuating disease pressures. Therefore, obviously the ecology of multicellular organisms’ microbial flora is essential to properly characterize. One element of the project involves genomics. This is not so easy for microbes because we don’t have the reference sequences of most of these organisms. We rely mostly on species which are easy to culture, and that does not include most lineages in the wild. That being said, there are workarounds, such as looking at the 16S rNA sequence, which is strongly constrained in bacterial lineages (i.e., it can serve as a “clock” to measure divergence of very deeply separated lineages).

With that, a new paper, Promiscuity in mice is associated with increased vaginal bacterial diversity:

Differences in the number of sexual partners (i.e., mating system) have the potential to exert a strong influence on the bacterial communities present in reproductive structures like the vagina. Because this structure serves as a conduit for gametes, bacteria present there may have a pronounced, direct effect on host reproductive success. As a first step towards the identification of the relationship between sexual behavior and potentially pathogenic bacterial communities inhabiting vital reproductive structures, as well as their potential effects on fitness, I sought to quantify differences in bacterial diversity in a promiscuous and monogamous mammal species. To accomplish this, I used two sympatric species ofPeromyscus rodents—Peromyscus californicus and Peromyscus maniculatus that differ with regard to the number of sexual partners per individual to test the hypothesis that bacterial diversity should be greater in the promiscuous P. maniculatus relative to the monogamous P. californicus. As predicted, phylogenetically controlled and operational taxonomic unit-based indices of bacterial diversity indicated that diversity is greater in the promiscuous species. These results provide important new insights into the effects of mating system on bacterial diversity in free-living vertebrates, and may suggest a potential cost of promiscuity.

These two species are sympatric and exhibit very different behaviors. Sympatric means that they aren’t geographically separated, so they are subject to the same environmental conditions. Rather, their distinctions on the species level seem to be due to behavior, in this case, the number of sexual partners of females. This then is a nice test for assessing the relationship of microbial diversity in the vagina as a function of partners. I suspect a priori you’d expect a positive relationship. And that’s what the author found. He presented a diversity index, but the results are rather intelligible visually. You can see clearly that the promiscuous species is characterized by a greater range of species richness than the monogamous one.

There are some studies of metagenomics of bacterial communities in humans. But to my knowledge it doesn’t look like there are any which have attempted to correlate number of sexual partners to diversity of vaginal flora. This is possible very important as a long term issue. The evolutionary biologist Paul Ewald has been reporting that there is a connection between history of infection and many late in life diseases, such as cancers. Mike Snyder had Stanford has been tracking his own biomarkers in extensive detail for several years, and has indicated that his own onset of Type II Diabetes was probably triggered by an earlier infection. These inferences were only possible because of his extremely rich personal data set, part of a broader project in his laboratory. But, it might give us a window into the more precise individual etiologies of diseases.

Citation: Naturwissenschaften. 2011 Nov;98(11):951-60. Epub 2011 Oct 1

Image Credit: Wikipedia, Wikipedia.

October 1, 2011

Up with nurses! Down with doctorates!

Filed under: Medicine — Razib Khan @ 12:48 pm

In light of growing health care costs and the demographic reality of an aging profession stories like this one in The New York Times are both depressing and hopeful. Calling the Nurse ‘Doctor,’ a Title Physicians Oppose:

But while all physician organizations support the idea of teamwork, not all physicians are willing to surrender the traditional understanding that they should be the ones to lead the team. Their training is so extensive, physicians argue, that they alone should diagnose illnesses. Nurses respond that they are perfectly capable of recognizing a vast majority of patient problems, and they have the studies to prove it. The battle over the title “doctor” is in many ways a proxy for this larger struggle.

Six to eight years of collegiate and graduate education generally earn pharmacists, physical therapists and nurses the right to call themselves “doctors,” compared with nearly twice that many years of training for most physicians. For decades, a bachelor’s degree was all that was required to become a pharmacist. That changed in 2004 when a doctorate replaced the bachelor’s degree as the minimum needed to practice. Physical therapists once needed only bachelor’s degrees, too, but the profession will require doctorates of all students by 2015 — the same year that nursing leaders intend to require doctorates of all those becoming nurse practitioners.

Nursing is filled with multiple specialties requiring varying levels of education, from a high school equivalency degree for nursing assistants to a master’s degree for nurse practitioners. Those wishing to become nurse anesthetists will soon be required to earn doctorates, but otherwise there are presently no practical or clinical differences between nurses who earn master’s degrees and those who get doctorates.


I applaud the wider distribution of medical services outside of the licensing monopoly of M.D.s. As an empirical matter I think there was a practical reason for the professionalization of medicine in the 20th century and the emergence of degree holding as necessary. To be frank about it for most of human history doctors were frauds or butchers. Modern medicine in the 20th century was a major revolution in that sense (though doctors are only part of it, the rise of an effective pharmaceutical industry is probably just as important if not more so). But the arrow of history does not always move in one direction, and we live in an “information age.” Doctors are human, and therefore fallible. They need the aid of both their patients and various other medical professionals to optimize health outcomes. The paternalistic model is just not viable in the long run, especially as the median educational qualifications of their patients keeps rising.

But notice that in this case we’re seeing greater and greater credentialism in fields which were traditionally perceived to be auxiliary to medical doctors. This is not a good sign. Instead of challenging the unquestioned prominence of medical doctors in domains where nurses are sufficient and more cost effective, the nursing profession is “fighting fire with fire.” This is not going to end well. Having to pile on education removes productive years in the work force. This is justifiable when education results in gains in productivity, but just as in education, I suspect that all the extra years for physical therapists and nurses is not doing anything but signalling, and further tightening up labor supply as the number of patients keeps on increasing because of the aging of the population.

August 15, 2011

Getting better sperm donors

Filed under: Genetics,Medicine,Sperm donors — Razib Khan @ 10:53 pm

The British newspapers have been reporting on a bizarre story about a Dutch sperm donor who hid a history of mental problems from recipients. I didn’t pay much attention to it because of the British tabloid media’s tendency to sensationalize. But Radio Netherlands also reported the outlines of the story, and there seems to be validity to the broad facts at hand. A Dutch man with a history of mental illness did father many children by offering his services online, and hiding various conditions from potential mothers. Now several of the children have developed the same problems (e.g., autism).


But the specific case here highlights some constraints on sperm donation which seem to have resulted in a “gray market” which allowed this man to “slip through” the safeguards. And yet I wonder why there is so much regulation of sperm banks in the first place? It reminds me of a story from a few years back about panic in Turkey over the importation of “foreign sperm.” Is there is a strong public policy reason why we should have a sperm donor shortage? In an ideal world children should know their parents, but there are far greater social ...

August 10, 2011

Crohn’s disease is about barely keeping you alive

The Pith: Natural selection is a quick & dirty operator. When subject to novel environments it can react rapidly, bringing both the good and the bad. The key toward successful adaptation is not perfection, but being better than the alternatives. This may mean that many contemporary diseases are side effects of past evolutionary genetic compromises.

The above is a figure from a recent paper which just came out in Molecular Biology and Evolution, Crohn’s disease and genetic hitchhiking at IBD5. You probably have heard about Crohn’s disease before, there are hundreds of thousands of Americans afflicted with it. It’s an inflammatory bowel ailment, and it can be debilitating even to very young people. The prevalence also varies quite a bit by population. Why? It could be something in the environment (e.g., different diet) or genetic predisposition, or some combination. What the figure above purports to illustrate is the correlation between Crohn’s disease and the expansion of the agricultural lifestyle.

But don’t get overexcited Paleos! There are many moving parts to this story, and I need to back up to the beginning. The tens of thousands of ...

July 25, 2011

Dominance, the social construct that confuses

Filed under: Dominance,Genetics,Health,Medicine,Penetrance,Sickle cell — Razib Khan @ 12:31 pm

A story in The Los Angeles Times seems to point medical implications of being a sickle cell carrier, Sickle cell trait: The silent killer:

At least 17 high school and college athletes’ deaths have been tied to sickle cell trait during the past 11 years. The group includes Olivier Louis, a player at Wekiva High School near Orlando, who died on Sept. 7, 2010, following his first football practice.

You have surely heard about sickle cell anemia. It is a recessive disease which expresses in those who carry two sickle cell alleles. T-boz of TLC has the disease for example due to her homozygosity. But the allele also famously confers some resistance against malaria, which explains its concentration in regions which have historically been malarial. Sickle cell is arguable the classic case of heterozygote advantage driving the emergence of a recessive disease. The frequency of the allele is balanced at the equipoise between the proportion of people who are more susceptible to malaria if its proportion is too low and those who express sickle cell anemia if its proportion is too high. This advantage is obviously context sensitive. The ...

July 20, 2011

Bacteria tell the tale of human intercourse

Filed under: Anthroplogy,Austro-Asiatic,Genetics,H. pylori,Medicine,Southeast Asia — Razib Khan @ 12:39 am

The Pith: the genetic relationships between bacteria in our stomach can tell us a lot about the relationships between various groups of people. Additionally, the distribution of different strains of bacteria may have significant public health implications.

The above image is from a paper which was pushed online yesterday in PLoS ONE: Evolutionary History of Helicobacter pylori Sequences Reflect Past Human Migrations in Southeast Asia. It’s a paper which caught my attention for several reasons. First, I’ve exhibited some curiosity about the history and prehistory of Southeast Asia of late. Elucidating this region’s historical dynamics may bear upon more general questions of human evolutionary and cultural process. Second, H. pylori is a fascinating organism whose connection to specific human populations is tight enough that it can shed light on past interactions of different groups. In short, just like humans H. pylori exhibits regional specificity and local history. But additionally, H. pylori is also subject to natural selection after introduction into a new population, and so can serve as a window upon cultural contacts which might otherwise leave a light demographic footprint. In other words, the spread of ...

June 12, 2011

You are a mutant!

ResearchBlogging.org
The Pith: You are expected to have 30 new mutations which differentiate you from your parents. But, there is wiggle room around this number, and you may have more or less. This number may vary across siblings, and explain differences across siblings. Additionally, previously used estimates of mutation rates which may have been too high by a factor of 2. This may push the “last common ancestor” of many human and human-related lineages back by a factor of 2 in terms of time.

There’s a new letter in Nature Genetics on de novo mutations in humans which is sending the headline writers in the press into a natural frenzy trying to “hook” the results into the X-Men franchise. I implicitly assume most people understand that they all have new genetic mutations specific and identifiable to them. The important issue in relation to “mutants” as commonly understood is that they have salient identifiable phenotypes, not that they have subtle genetic variants which are invisible to us. Another implicit aspect is that phenotypes are an accurate signal or representation of high underlying mutational load. In other words, if you can see that someone is weird in ...

April 13, 2011

When the doctor is a patient….

Filed under: Health,Medicine — Razib Khan @ 11:17 pm

So I’ve been seeing headlines like this today: Physicians Recommend Different Treatments for Patients Than They Choose for Themselves, Study Finds. Here are the numbers:

A total of 242 physicians returned the colon cancer questionnaire (response rate of 48.4 percent), and when asked to imagine they had received the cancer diagnosis, 37.8 percent of physicians chose the surgical procedure with a higher rate of death, but a lower rate of adverse effects. Conversely, when asked to make a recommendation for a patient, only 24.5 percent of physicians chose this option.

The second scenario asked 1,600 physicians to imagine that a new strain of avian influenza had just arrived in the U.S. One group of physicians were asked to imagine they had been infected, and the other group was asked to imagine that his or her patient was infected. One treatment was available for this strain of influenza: an immunoglobulin treatment, without which persons who contract flu have a 10 percent death rate and a 30 percent hospitalization rate with an average stay of one week. The treatment would reduce the rate of adverse events by half, however it also causes death in 1 percent of patients and permanent neurological paralysis in ...

April 4, 2011

Fair & balanced on circumsion

Filed under: Circumcision,Health,Medicine — Razib Khan @ 10:48 am

When Michelle mentioned on Twitter that she was going to write about circumcision, I told her to expect some angry people to come out of the wood-work. Today she has a post up at Scientific American, What’s the deal with male circumcision and female cervical cancer? She concludes:

In addition, while it is true that women with circumcised partners are less likely to get cervical cancer, they are not immune. Women with circumcised partners still contract HPV and develop cervical cancer! They just do it at a reduced rate.

There are other methods that are much more likely to reduce a woman’s chance of contracting HPV and developing cervical cancer, such as vaccination and condom use. Therefore, from a public health standpoint in the United States, it may not be necessary to circumcise male babies solely for the purpose of reducing the risk of cervical cancer in his future sexual partners (of course, this doesn’t take into account the possibility that the child might not be heterosexual).

On the whole I think that Michelle’s take is reasonable and fair-minded. But, I think numbers are of the essence here. What is the expected reduction in rate of risk? This ...

February 14, 2011

Who are those Houston Gujus?

The figure to the left is a three dimensional representation of principal components 1, 2, and 3, generated from a sample of Gujaratis from Houston, and Chinese from Denver. When these two populations are pooled together the Chinese form a very homogeneous cluster. They don’t vary much across the three top explanatory dimensions of genetic variance. In contrast, the Gujaratis do vary. This is not surprising. In the supplements of Reconstructing Indian population history it was notable that the Gujaratis did tend to shake out into two distinct clusters in the PCAs. This is a finding you see over and over when you manipulate the HapMap Gujarati data set. In reality, there aren’t two equivalent clusters. Rather, there’s one “tight” cluster, which I will label “Gujarati_B” from now on in my data set, and another cluster, “Gujarati_A,” which really just consists of all the individuals who are outside of Gujarati_B cluster. Even when compared to other South Asian populations these two distinct categories persist in the HapMap Gujaratis.

Zack has already identified a major difference between the two clusters: Gujarat_A has some individuals with much more “West Eurasian” ancestry. ...

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