Genetics Made Complicated

noreply@blogger.com (K Lam) — Sat, 13 Nov 2010 15:42:00 +0000

Apologies for the long delay - I'm writing papers for publication. In the meantime, check out this comparison of CSI science vs real science at Forensic Science.

Science article for artificial life

noreply@blogger.com (K Lam) — Sat, 02 Oct 2010 16:08:00 +0000

Looks like the Science article for the artificial bacterial cell is publically available, so here's a link to the full text:

Creation of a Bacterial Cell Controlled by a Chemically Synthesized Genome - Gibson et al., 2010

For those who prefer PDF, look to the left of the article and you'll find a link.

Those of you who don't feel like going through it - no worries! My next post will be a breakdown of this article.

Intelligent design is real

noreply@blogger.com (K Lam) — Thu, 30 Sep 2010 20:52:00 +0000

This is an 18 minute video of Craig Venter announcing the creation of synthetic life. There so much to talk about with this one, and it's going to take multiple posts. Consider this, then, a bit of preview of some of the stuff I want to get into here in the future.

"Lies, damned lies and statistics."

noreply@blogger.com (K Lam) — Thu, 30 Sep 2010 00:01:00 +0000

Someone once said to me that it was easier to discuss statistics with someone who is ignorant of statistics rather than someone who knows a little bit about it, as the person who has some knowledge will probably get it wrong. This is largely, I suspect, because it's very easy to overlook assumptions and seemingly minor bits of information which turn out to be extremely important.

This is a 20 minute TEDtalk from 2005 which I quite like which illustrates that point.

PS. If you've never been to TED, you ought to. There are plenty of really interesting talks there.

Why creationism makes a better scientific theory than intelligent design

noreply@blogger.com (K Lam) — Thu, 23 Sep 2010 21:05:00 +0000

The scientific method looks something like this:

1. Make an observation: Things fall down.

2. Think up some explanation for that observation. This is a hypothesis: There is a force between objects which draws them together.

3. Make a prediction based on the hypothesis: The amount of force is based on mass.

4. Devise an experiment to test the the prediction: Build an instrument which would be able to measure the attractive force between objects. See if the attractive force - if it’s there! - correlates with mass.

If the predicted observation doesn’t happen, you reject the hypothesis and go back to the drawing board, using the new observations that you’ve collected to build a better hypothesis. If the predicted observation does happen, you see if the results are reproducible and consistent. When you’re really sure that that what you’ve got isn’t a chance anomaly but a repeatable, consistent observation, then you put a little checkmark next to the hypothesis and say, “We’re pretty sure this is a good explanation.” A scientific theory could be thought of as a group of hypotheses intended to explain related phenomena. A good scientific theory is one which has lots of supporting evidence - that is, it has been used to make lots of testable predictions which have led to repeatable, consistent observations that support the hypotheses. A bad scientific theory does not make accurate predictions.

It turns out that creationism (by which I mean things like Young Earth Creationism) has all the makings of a (bad) scientific theory while intelligent design (ID) does not, even though ID claims to be scientific. It’s all in how science is structured.

Creationism as scientific theory

When you structure creationism* like a scientific theory, it looks like this:

1. Observation: There is holy scripture which describes the origin of the universe, life and everything.

2. Hypothesis: The holy scripture is a literal description of the origin of the universe, life and everything.

3. Prediction: The holy scripture says that the Earth is 5000-10000 years old.

4. Experiment: Estimate the age of the Earth through the use of radiometric age dating or some other acceptable and technically sound method of dating**.

Structurally, everything fits. You can test creationism scientifically, and you can even modify the hypothesis to try again. Admittedly, this modification is usually done by asserting that the holy scripture in question isn’t a literal description of the origin of the universe, life and everything, which in turn is just a fancy way of saying, “The explanation isn’t in the holy scripture.”

ID as scientific theory

1. Observation: There are some really complex stuff in nature. That stuff is so complex that even removing one little bit makes it impossible for the complex part to do what it does (this is called irreducible complexity). A common, non-biological example is a mouse trap. Take away any part, and it ceases to function as a mouse trap.

2. Hypothesis: Some unknown designer created or designed the complex stuff in nature.

3. Prediction: ???

Let’s set aside for a minute the questionable nature of the originating observation (though go see this wikipedia article for a more thorough explanation of irreducible complexity and criticisms), ID proponents will try to tell you that they predict that there will be other irreducibly complex stuff. That’s not a prediction. That’s the originating observation. When you observe that stuff falls down, you can’t drop a ball and go “Hey, it fell down! So my theory of invisible spirits pulling stuff down is true!”

All right, what else? Some might argue that you can come up with some testable predictions of the unknown designer. The problem is that there’s virtually nothing to go on about this unknown designer. ID proponents have claimed that they are not affiliated with a religion, so you can’t rely on holy scripture, like creationists. In this situation, aliens, Sauron, the flying spaghetti monster, invisible pink unicorns and any other entity who could have some form of “designing” power are fair game. So, how do you choose which one to pursue? What other observation do you have which allows you to make any assertions about the unknown designer, especially when ID doesn’t require that the designer design more than once? “I have evidence of aliens!” is all well and good, but you need to connect aliens to the irreducibly complex thing.

What ID proponents want you to believe is that the prediction “The theory of evolution is wrong” is an acceptable prediction for ID. Yes, if ID is a correct explanation then the theory of evolution might be wrong, but this is not an acceptable prediction based on scientific method. Which is a pretty good thing for ID supporters, since if it was then it would be acceptable to say that if the theory of evolution is true, then ID is wrong. And since there is a lovely pile of evidence supported through the use of the scientific method, for the theory of evolution, this would mean that ID would be “proven” wrong.

Which is why ID is gaining momentum while creationism is sliding to the wayside. Creationism leads to testable predictions and can be subjected to the scientific method***. Intelligent Design can’t but that also means that you can’t use the scientific method to refute it.

* While I mean young earth creationism here, you could probably slide in any religion with holy scripture which is meant to be taken literally.
** For more on the methods used to date the Earth, here’s a Wikipedia article. As it turns out, the Earth is about 4.54 billion years old.
*** That the scientific method often shows that literal interpretation of holy scriptures is faulty is another story.

A genetics primer

noreply@blogger.com (K Lam) — Sat, 18 Sep 2010 05:38:00 +0000

When I write posts, I try to keep the jargon down to a minimum and explain the terms that I use. I don't want to turn this into a primer about genetics blog, as there are plenty of resources that exist. Of course, the problem is finding a good one when you aren't sure about your knowledge to begin with....

That being said, I recently stumbled across the Learn. Genetics^TM site, maintained by the University of Utah. Instead of the usual wall of text, they have little flash animations which make the info easier to absorb. There are also interactive modules and virtual labs so you can try out techniques that are used in laboratories during molecular studies. I have to admit to a certain amount of geeky glee as I cloned a virtual mouse.

I like this site well enough to put a link to it on the side. If you feel like playing around in a virtual lab and picking up some basic genetics, go check it out!

Is Race Genetic addendum

noreply@blogger.com (K Lam) — Fri, 17 Sep 2010 00:39:00 +0000

In my Is Race Genetic? series, I didn't really touch on the implications of using race as a way of telling if someone is more likely to be susceptible to certain diseases, or if they are going to respond adversely/favourably to a particular medical treatment. In case you're curious, here's a link to a paper called "Genetic variation, classification and 'race'" by Jorde and Wooding published in 2004*.

To quote the abstract:

New genetic data has enabled scientists to re-examine the relationship between human genetic variation and 'race'. We review the results of genetic analyses that show that human genetic variation is geographically structured, in accord with historical patterns of gene flow and genetic drift. Analysis of many loci now yields reasonably accurate estimates of genetic similarity among individuals, rather than populations. Clustering of individuals is correlated with geographic origin or ancestry. These clusters are also correlated with some traditional concepts of race, but the correlations are imperfect because genetic variation tends to be distributed in a continuous, overlapping fashion among populations. Therefore, ancestry, or even race, may in some cases prove useful in the biomedical setting, but direct assessment of disease-related genetic variation will ultimately yield more accurate and beneficial information.

When they get into examples, the jargon gets a little heavy but the main points they're trying to make are pretty good. If you've read my series, you'll probably want to scroll down to the section called "Genetic variation, race and medicine."

*Those of you who pay attention to detail will notice that this was published before Witherspoon et al.'s paper, which I talked about in the series. That's okay - I think their points still stand.

On the Origin of Species

noreply@blogger.com (K Lam) — Wed, 15 Sep 2010 21:01:00 +0000

I was watching some criticism of creationist and intelligent design (ID) rhetoric yesterday (here's the link to the first vid of the playlist) and it occurred to me that the term "Darwinist" comes up a lot. It's something that I've seen quite a bit but not something I've really thought of. In its most benign* sense, it means someone who believes in the mechanisms and theories proposed by Charles Darwin. To be fair, Darwin's book On the Origin of Species was pretty influential in changing the way we think about species, biology and laid the groundwork for the theory of evolution. It's no surprise that it's the book that creation/ID advocates attack.

The problem with this tactic is that the book is out-of-date, and the scientific community knows it.

The book was first published in 1859. That's over 150 years ago. In that time, the scientific community hasn't been sitting idly by. It's been testing the theory of evolution, seeing if the things it predicts do actually occur, and modifying the theory as necessary so that it provides a better explanation for things that we can observe**. Attacking modern evolutionary theory by attacking Darwin's book is like attacking modern cultural mores by attacking Jane Eyre (published in 1847). Or like attacking Einstein's theory of relativity by attempting to dismantle Newtonian physics.

In short, I'm not a Darwinist. Heck, I haven't even read the book except for a few passages - I find it long-winded and dry***. I do believe that evolution happens, though, and after examining evidence I am convinced that natural selection is one of the mechanisms by which evolution occurs. I'll tip my hat to Darwin for that.

* Note that I use the word "benign" and not "objective." The label "Darwinist" is not intended to be objective.

** The things we can observe today are vastly more numerous than what Darwin could see. Think back ten years to all the gadgets that used to be available to you, and all the ones that are available to you now. Now, think about 150 years of technological advancement which can be applied to scientific study. I think Darwin would faint at some of the stuff we can look at now.

*** If you wanted to take it out for a spin, you can find electronic copies on Project Gutenberg. Just search by title. You can also find Jane Eyre, if you're so inclined.

The Intrusion of Life

noreply@blogger.com (K Lam) — Tue, 14 Sep 2010 21:56:00 +0000

For those of you few who may be wondering what in the world happened to me, let me just briefly say that my thesis happened. In the past several months, I have written my thesis, defended it, and completed the revisions. I'm in the process of writing some papers for publication, but the major time consumer of my life has been dealt with.

What that means is that I will be working over the next couple of weeks to revamp this blog. My goal is to start slow but steady - a post a week, at least. We'll see how things go from there.

Is Race Genetic? Part IV: Teasing Apart Race, Populations and Genetics

noreply@blogger.com (K Lam) — Wed, 25 Nov 2009 23:49:00 +0000

Many apologies for the lateness of this post.

Previous parts: Part I, Part II, Part III

You may have noticed in previous parts of this series that I use the term "population" more often than "race." This is deliberate: if you want to determine if race is genetic, you can't assume that the genetic populations into which you divide individuals are synonymous with race. You have to first see if it's possible to divide individuals based on genetic characteristics and then determine if those populations correspond to what we call races.

In Part I, I said that a population is "is a distinct group of interbreeding people, often associated with geography. For instance, a population might be the group of people living in a single town." This is correct but not the full story. What the individuals of a population actually share is common ancestry. This isn't to say that we can pinpoint precisely the identities of these ancestors or that the individuals of a population are related in an appreciable fashion (by which I mean in a context that matters for social or cultural reasons). Nor does it mean that the humans of the world can be separated into more than one population. The belief that it's possible to separate people into genetic populations (for lack of a better term) is that geographic isolation and the issue of travel made it more likely that certain groups of people would breed amongst themselves, leading to allele frequencies being skewed in some direction or another. Natural selection might also work to skew allele frequencies. The question being answered by Witherspoon et al.'s study (not to mention many other studies) is whether or not there has been enough non-random breeding that certain populations have common ancestors that make them distinct from other populations.

With that in mind, let's break down the results that Witherspoon et al. got.

1. It's possible to separate groups of people into populations.

This is the obvious one. If you look at enough loci, it is possible to separate individuals into distinct populations. Furthermore, it is possible to separate individuals so that most individuals only belonged to one population.

2. Some individuals belonged to more than population.

Witherspoon et al. talked about individuals who had been misclassified because the methods for separating individuals placed them in a different population than what was expected. You may recall that the "expected" population was tied to the individual's race. If you look at the data, what you find is that the individual wasn't classified into the wrong population so much as the individual was a fringe case who could have potentially belonged to more than one population. The sorting method arbitrarily put the individual into one population or the other because the sorting method didn't allow for the possibility that the individual could belong to more than one population. If populations are caused by common ancestry, however, then an individual who gets sorted into more than one population is simply an individual who shares common ancestors with individuals from more than one population. When you consider that there was almost always individuals who could not be sorted into a single population in groups of people living very close to each other (where, presumably, breeding between groups could occur), this should come as no surprise.

3. The study looked at hundreds of loci, many of which have no obvious effect.

In order to make the "misclassfication" rate as low as possible, Witherspoon et al. often looked at hundreds of different loci. Many of those loci (I even venture to say most, though I can't confirm that) have no physical effect whatsoever. I don't want to get into excessive detail about basic biology, but it relies on the idea that any differences in the DNA is inheritable, whether it has a physical effect or not. Changing a single base in the DNA sequence may have no effect whatsoever (because of the redundant nature of the DNA code, or because it's in an area which doesn't code for anything) but it's still a change that can be called a different allele. It's kind of like the difference between "colour" and "color." The spelling is slightly different, but they mean the same thing.

4. Populations are not divided by the absence or presence of a few traits but, rather, by frequencies of alleles.

This is tied closely to 3. If it took simply the presence or absence of a few traits/alleles to differentiate populations, Witherspoon et al. would not have had to look at the frequency of hundreds of alleles in order to separate populations which were very far away from each other. This means that it is nigh on impossible to find an allele which is only every found in one population and never found in another population. It may be true that 99% of the individuals of Population A will have allele X while only 1% of Population B will have allele X, but allele X still persists in Population B and its existence isn't sufficient to sort an individual into one population or another. This also ties to the idea that sometimes you can find individuals between populations who are more similar than individuals within a population.

So, now we know lots of populations. The next question is whether those populations correspond to races. Since Witherspoon et al. could classify individuals into the expected populations defined by race, it would be fair to say that there is a correlation between race and genetic population. It would also be fair, however, to say that the correlation is not perfect. If we're just talking about genetic populations, then "misclassification" isn't an issue. It was, however, in Witherspoon et al.'s study, since the individuals were identified as part of a distinct race, and some could be classified into the wrong race. It could, of course, be argued that these individuals were "mixed-race" and were not misclassified at all - they were simply misidentified from the start. That would make the correlation between populations and races very strong, wouldn't it?

Of course, if genetic populations and races are the same thing, then it would mean that all the things we learned about populations applies to races. Races would be defined by hundreds of differences which have no discernible effect whatsoever on an individual's actual physical characteristics; the differences would be based on shared ancestry. The presence or absence of a few traits would be insufficient to classify an individual into a particular race, and no trait "belongs" to one race or another - they would be present in all races. Individuals between races could be more similar than individuals within the same race.

That actually doesn't sound too bad to me. The problem, of course, is that the question "Is race genetic?" isn't actually about finding out of people can genetically be split into populations defined by allele frequencies. It's about whether or not we can find a biological basis for concretely separating people into different groups which fit with the ways we've already decided to use to separate people. We want to be able to look at a person and say, "He belongs to race A because he has blue skin. She belongs to race B because she has orange skin." Instead, the data shows us that all we can do is say, "Well, he probably belongs to race A because there are more people with blue skin there. And she probably belongs to race B because there are more people with orange skin there. And, actually, they could both belong to race C. Or maybe skin colour has nothing to do with it. Let me check a hundred more loci...."

Race may correlate with genetic population, but a genetic population is not a race. Race transcends the biological, involving culture, language, upbringing, place of origin, and a host of other factors. I'd even say that these factors are even more important the biological, mainly because the biological says that we're really not all that different.

Reference
1. Witherspoon, DJ, Wooding, S, Rogers, AR, Marchani, EE, Watkins, WS, Batzer MA, Jorde, LB. 2007. Genetic similarities within and between human populations. Genetics 176: 351-359.

Is Race Genetic? Part III - Witherspoon et al. Bring it Together

noreply@blogger.com (K Lam) — Fri, 06 Nov 2009 18:25:00 +0000

Previous parts: Part I, Part II

In a 2007 paper, Witherspoon et al.¹ addressed the problem of reconciling three facts:

1. Genetic variation between major human populations (races) account for only a small fraction of allele frequency variation.

2. Multilocus statistics are capable of accurately assigning most individuals to the correct population of origin.

3. Individuals from different populations can still be more similar than individuals from the same population.

It's possible that the reason these facts emerged is because previous studies didn't look at the same populations. To determine if there's merit to these facts or if they are a product of the sample populations, Witherspoon et al. undertook a massive amount of data analysis. They used three different data sets, each focusing on a different kind of polymorphic locus, with loci numbers ranging from 175 to well into the thousands. The individuals were already divided into populations based on race. To measure the genetic similarities/dissimilarities between individuals, they calculated the "pairwise genetic distance." The pairwise genetic distance compares two individuals (hence the "pairwise") and determines the "genetic distance" between them based on their shared alleles. If, at a particular locus, two individuals share more alleles, they will have a smaller genetic distance. The overall pairwise genetic distance between two individuals is average of their per-locus distances.

Witherspoon et al. were interested in three values*:

1. Dissimilarity Fraction (DF): The DF is a measurement of "the probability that a pair of individuals randomly chosen from different populations is genetically more similar than an independent pair chosen from any single population." To determine it, they paired up all the individuals in all possible combinations and determined the pairwise genetic distance for each combination. These pairwise genetic distances could be classified as within- or between-population distances depending on how the individuals had been divided into populations based on race. They then calculated the frequency with which the within-population distances is greater than the between-population distances. If the frequency is very low, then it would mean that individuals are usually (if not always) more similar to members of their own population than to members of another population. If the frequency is high, the opposite is true.

2. Centroid Misclassification Rate (CMR): The CMR makes use of a modified pairwise genetic distance calculation, comparing each individual to the "centroid" of each population rather than to every other individual. The centroid is a pretend individual whose genetic makeup is the average of all the genetic information of the population. Essentially, it's like calculating the pairwise genetic distance to the average of all other individuals of the target population. Individuals get assigned to the population with the most similar centroid. The CMR is the proportion of individuals who get misclassified.

3. Population Trait Value Misclassification Rate (PMR): The PMR doesn't make use of the pairwise genetic distance calculation. Instead, it is based on the simplified model proposed by Edwards² which I discussed in the previous post. In order to divide individuals into separate populations, you take two populations (say, A and B) and look at any particular locus. The allele which is more frequent in Population A is given a value of 0 while the allele which is more frequent in Population B is given a value of 1. An individual gets assigned a value at that locus based on the average of the values of his/her alleles at that locus. To determine the "population trait" value of the individual, you take an average of all the values at all the loci. A cutoff point is calculated based on the average population trait values of all individuals in Population A and Population B. If the individual is above the cutoff point, he/she is assigned to Population B. If the individual is below the cutoff point, he/she is assigned to Population A. Since this method is limited in that it can only divide individuals into two populations, Witherspoon et al. only considered an individual assigned to a particular population if, in all combinations where populations were paired off and population traits calculated, the individual was always assigned to the same population. The PMR, then, is the rate at which individuals were either misclassified or not classified at all.

As you may have noticed PMR and CMR are both methods for determining how accurately individuals get assigned to populations while DF is a measure how distinctive those populations are from each other. You would expect that all three values would act in the same way. That is, if DF goes down, so should CMR and PMR; if PMR goes up, so should CMR and DF, etc. So, what did Witherspoon et al. find?

First, they found that DF, CMR and PMR did follow the same trends. However, they discovered that DF decreases far more slowly than CMR and PMR. This is because both CMR and PMR don't compare individuals to individuals; instead, they compare individuals to aggregated information. CMR depends on a method which compares individuals to centroids rather than real people while PMR depends on a method which relies on allele frequency comparisons between populations. A lot of variation gets smoothed out. DF, on the other hand, is based on a method which compares individuals directly and is affected by the high amount of variation within groups. In other words, when comparing individuals to each other, you get pick up on a lot of their similarities as well as differences, and those can count for a lot. When comparing individuals to aggregated population information, only the trends matter.

Second, the number of loci used is important. The more loci used, the lower the values of DF, CMR and PMR. This is because as you get more information, you get a better chance of accurately correlating data or finding differences between individuals. In certain circumstances (more on that below), if you get enough data from enough loci DF, CMR and PMR approach 0%. In other words, with enough information, it is possible to always accurately assign someone to a population and that individual will never be more similar to someone from a different population.

Third, the closeness of the populations matter. When populations are geographically distinct and there is little chance of breeding between populations, DF, CMR and PMR can become negligible, though in the case of DF you will need to have information from thousands of loci. When populations are more closely related to each other (due to less geographical distinctiveness and more historical breeding between populations), then DF, CMF and PMR never reach 0%, even when over 10,000 loci are used.

In summary, Witherspoon et al. show that it's not contradictory for individuals between populations to be more similar than individuals within populations while still having accurate population assignment of individuals. Within population diversity can be exceptionally high, and distinct populations really do exist.

So, does that mean that race really is genetic? Nope. Or, I should say, not exactly.

Tune in for Part IV - Teasing Apart Race, Populations and Genetics

* These aren't the symbols/abbreviations that are used in the paper, but I think the ones that I'm using here are a little easier to follow.

1. Witherspoon, DJ, Wooding, S, Rogers, AR, Marchani, EE, Watkins, WS, Batzer MA, Jorde, LB. 2007. Genetic similarities within and between human populations. Genetics 176: 351-359.

2. Edwards, AW. 2003. Human genetic diversity: Lewontin's fallacy. BioEssays 25: 798-801.

Is Race Genetic? Part II - Lewontin's Fallacy

noreply@blogger.com (K Lam) — Wed, 04 Nov 2009 17:03:00 +0000

Part I here

First, a quick reminder of the last post: Lewontin's study statistical analysis involved looking at the genetic diversity of 17 different loci and he concluded that most of the genetic diversity was due to individuals being individuals, not because of any racial grouping. Therefore, racial groupings are obsolete.

In the 2003 paper Human genetic diversity: Lewontin's fallacy¹, A. W. F. Edwards wrote:

It is not true that "racial classification is... of virtually no genetic or taxonomic significance". It is not true, as Nature claimed, that "two random individuals from any one group are almost as different as any two random individuals from the entire world", and it is not true, as the New Scientist claimed, that "two individuals are different because they are individuals, not because they belong to different races" and that "you can't predict someone's race by their genes".

Them's fightin' words! Let's see what guns he brings to the duel.

Edwards wrote, "There is nothing wrong with Lewontin's statistical analysis of variation, only with the belief that it is relevant to classification." In other words, he doesn't dispute Lewontin's findings but rather how they should be interpreted. Edwards claims that, while diversity can be important, it's the correlations between the genes that differentiates races, not the diversity. If you correlate multiple genes, it becomes possible to reliably determine to which population a person belongs, and those populations can correlate with what we call race. In other words, you really could look at someone's genes and figure out their race.

Let's make up a simple example. In Population A, half the people have blue hair while the other half have green.* In Population B, this is true as well. This means that if you've got someone standing in front of you with green hair, you can't tell to which population he belongs. Now, let's add in eye colour (red and purple). Half the people of Population A have red eyes while the other half have purple eyes. This also holds true for Population B. To which population does a red-eyed, green-haired person belong? Based on Lewontin's analysis, you wouldn't be able tell. Edwards points out that you can look how eye colour and hair colour correlate with each other. If red eyes and green hair tended to correlate together in Population A while purple eyes and green hair correlate in Population B, then you could guess that the red-eyed, green-haired person belongs to Population A.

Statistical methods allows you to factor in allele frequencies as well as how alleles correlate with each other. As you add more genes with more alleles into the mix, it becomes increasingly likely that you'll be able to accurately predict to which population a person belongs. Edwards calculates that, using data which simulates Lewontin's level of within/without population diversity and assuming only two different alleles at each locus, you need to correlate about 20 traits before the chance of misclassifying someone into the wrong population becomes negligible (below 1%). Studies using actual data from individuals have shown "genetic affinities that have unsurprising geographic, linguistic and cultural parallels." In other words, researchers could look at a pool of individuals and, by using statistics, cluster the individuals into populations based on various polymorphic loci, and those clusters could correspond to what we call "race."

So, despite the high amount of within population diversity, it looks like there really is a genetic basis for race. But hold on! In 2004, Bamshad et al.² published a paper using multilocus statistics (that is, the kind of correlation statistics that Edwards advocates) and nearly 400 polymorphic loci that showed that two individuals from different populations could often be more similar than two individuals from the same population. What gives?

Check out Part III - Witherspoon et al. Bring it Together

*I'm picking physical characteristics for this example because they're easily visualized, not because they make good loci.

1. Edwards, AW. 2003. Human genetic diversity: Lewontin's fallacy. BioEssays 25: 798-801.

2. Bamshad, M, Wooding, S, Salisbury, BA and Stephens, JC. 2004. Deconstructing the relationship between genetics and race. Natural Reviews Genetics 5: 598-609.

Is Race Genetic? Part I - Lewontin 1972

noreply@blogger.com (K Lam) — Tue, 03 Nov 2009 19:18:00 +0000

The idea that there is more diversity within races than between races has been floating around for a few decades. It's origin is in a 1972 paper published by Richard Lewontin called "The Apportionment of Human Diversity"¹. Let's have a go at what he actually did.

First, he divided people into a hierarchical scheme:

population--> race--> species (Home sapiens)

A population is a distinct group of interbreeding people, often associated with geography. For instance, a population might be the group of people living in a single town. A race would therefore be a larger group of people to which several populations belong. For his paper, Lewontin classified populations into 7 races: Caucasian, African, Mongoloid, S. Asian Aborigines, Amerinds, Oceanians, and Australian Aborigines. The final level was Home sapiens itself. The hierarchical setup is necessary to make the "within race/between race" distinction. Arguably, individuals within a population will be more genetically similar to each other than to another population. This makes sense since they are living in the same environment, breeding with each other, etc. If race is an important factor, then populations will be more genetically similar to other populations within the same racial group than to populations in a different racial group.

Looking at it from another direction, let's say I have Population A in Race X. It has a genetic diversity of 1 (this is a made-up number that doesn't mean anything real; assume that the lower the number, the lower the genetic diversity). Population B of Race X has a genetic diversity of 1 as well. When I mix the data from Population A and Population B together, I get a genetic diversity of 4. This makes sense if Population A and Population B are genetically similar within the populations but there are differences between the populations. If racial groupings can be determined using genetics, then I would expect that if Population A was from Race X but Population B was from Race Y, then the genetic diversity would increase a lot (to, say, 87).

Clearly, then, everything hinges on what we mean by genetic diversity. In Lewontin's paper, he looked at 17 different polymorphic loci. Essentially, this means that he looked at different regions of DNA which can show differences between people. Note that I didn't say "genes." A polymorphic locus does not need to be connected to any gene (though it can be). It simply must be a stretch of DNA which is sometimes different in different people. Each different version of the locus is called an allele. Looking at many different loci makes it more likely that you'll be able to find real differences or similarities, rather than an anomaly that might exist at a single locus. To determine diversity, he looked at the frequency of the alleles at each locus. The more alleles there are, the more diverse it is (because there are more versions of the locus); the more equal the frequencies of the alleles, the more diverse the population (because if one allele was at a very high frequency, then more people would be the same, leading to less diversity).

After some number crunching, Lewontin found:

The mean proportion of the total species diversity that is contained within populations is 85.4%.... Less than 15% of all human genetic diversity is accounted for by differences between human groups! Moreover, the difference between populations within a race accounts for an additional 8.3%, so that only 6.3% is accounted for by racial classification.

What does that mean? When you start off with a single population, there will be a certain allele frequencies for each gene, and there will be a certain number of alleles in the population. When you pool another population with the first, you would expect a change to the allele frequencies and the number alleles unless the populations are very similar. As you add more populations, you would expect more diversity. Once you pooled all of the populations together, that should be the maximum diversity. So, when Lewontin found that 85.4% of total species diversity was found within a population, it means that when you look at a single population, 85.4% of the maximum diversity was already there. Add in more populations within the same race, and that accounted for another 8.3%. If you pooled all the races together, that accounted for the last 6.3%. Lewontin goes on to conclude:

It is clear that our perception of relatively large differences between human races and subgroups, as compared to the variation within these groups, is indeed a biased perception and that, based on randomly chosen genetic differences, human races and populations are remarkably similar to each other, with the largest part by far of human variation being accounted for by the differences between individuals. Human racial classification is of no social value and is positively destructive of social and human relations. Since such racial classification is now seen to be of virtually no genetic or taxonomicsignificance either,no justification can be offered for its continuance.

Though this seems cut and dried, it's not the entire picture. Check out Part II - Lewontin's Fallacy.

1. Lewontin RC. The apportionment of human diversity. In: Dobzhansky T, Hecht MK, Steere WC, editors. Evolutionary Biology 6. New York: Appleton-Century-Crofts. 1972. p 381–398.

Is Race Genetic? Part 0 - Preview

noreply@blogger.com (K Lam) — Mon, 02 Nov 2009 18:16:00 +0000

Over the next week or so, I'll be making posts about the genetic basis of race. My original intention was to make a post about the science and then go into the implications, but the subject turned out to have far more meat than I expected. The more you know....

As the posts come out, I will edit this post with links to each post so this one can act as a sort of index.

Parts:
Part I - Lewontin 1972
Part II - Lewontin's Fallacy
Part III - Witherspoon et al. Bring it Together
Part IV - Tease Apart Race, Populations and Genetics

Genomes Go Public

noreply@blogger.com (K Lam) — Thu, 29 Oct 2009 16:29:00 +0000

Scientific studies into human diseases or conditions rely heavily on volunteer participation and one of the usual prices for said participation is anonymity. In the past, anonymity has been fairly easy to guarantee. It's very hard to connect "Subject A, with weird disease X" to Bob Smith because, even if weird disease X is very rare, there are likely hundreds or thousands of people with disease X. Since only details relevant to the study are collected, there simply aren't enough identifying features of Subject A to definitively figure out his identity.

This simply isn't the case in genomics. By definition, genomics is the study of genomes. By studying someone's whole genome, we can elucidate the potential connection between the disease of interest and a person's genes, as well as identifying mitigating factors which can affect not only the course of the disease but also factors affecting treatment. The problem is that a person's genome is fairly unique. While Bob will still likely have functional anonymity, as it is unlikely that someone will go to the trouble to obtain an uncontaminated DNA sample and run expensive tests to connect him to the elusive Subject A, he does not have actual anonymity. Researchers must struggle with how to protect Bob's personal information while at the same time advancing their research. This raises new ethical dilemmas when you realize that one of the methods of advancing research is to share data between collaborating labs - but Bob may never interact with researchers beyond the first lab with which he was associated and may not be aware of how his information is spread.

There's actually a lot of thought and action taken on this, so please don't assume that personal information is being thrown haphazardly about in the wild scientific frontier. I bring it up to provide a bit of background on a novel solution to the problem, in which the guarantee of anonymity is abandoned altogether. The Personal Genome Project is project where volunteers can essentially donate their genomes to research. As it says on their frontpage:

We believe individuals from the general public have a vital role to play in making personal genomes useful. We are recruiting volunteers who are willing to share their genome sequence and many types of personal information with the research community and the general public, so that together we will be better able to advance our understanding of genetic and environmental contributions to human traits and to improve our ability to diagnose, treat, and prevent illness.

Scroll down to the bottom of the frontpage and you'll notice a CC0 universal waiver logo. In essence, the Personal Genome Project is making its research data as close to the public domain as it legally can. If you want, you can take a look at the first ten participants, called the PGP-10, and get not only bios but pictures. Ever wanted to know George Church's health history? There it is. Or how about Steven Pinker? Here you go.

As I understand it, becoming a part of the Personal Genome Project isn't as simple as sending a random tissue sample. There's a rather exacting consent process which requires, among other things, an entrance exam on which you must get 100% so they can be sure that you fully understand what you're getting into.

I suppose that, given the increasing prevalence of information sharing, I shouldn't be surprised that someone would try a genome project with the express purpose of making data public. It's an exciting prospect, but it's also kind of scary. Do you think it's a good idea? Would you participate? Would you encourage others to participate? What pitfalls do you think might occur? I'd love your comments!

"Gay Genes" Aren't Enough

noreply@blogger.com (K Lam) — Wed, 28 Oct 2009 14:15:00 +0000

On November 3, 2009, the voters of Maine vote to see if they will uphold the law which allows same-sex couples to get married. Back in April, an 86-year-old WWII veteran named Philip Spooner made a speech to Maine's Judiciary Committee supporting gay marriage; recently, the video of his speech has been rushing through the internet (here it is if you haven't seen it yet). To quote the part that got a standing ovation:

I am here today because of a conversation I had last June when I was voting. A woman at my polling place asked me, "Do you believe in equal, equality for gay and lesbian people?" I was pretty surprised to be asked a question like that. It made no sense to me. Finally I asked her, "What do you think our boys fought for at Omaha Beach?" I haven't seen much, so much blood and guts, so much suffering, much sacrifice. For what? For freedom and equality. These are the values that give America a great nation, one worth dying for.

This is a plea for the rights of homosexuals on the grounds of freedom, equality and human decency. In my mind, this is the right way to do it. The wrong way to do it is to make the case that homosexuality is a biological phenomenon.

The reasoning looks like this:

1. Homosexuality is not a choice but determined by biological factors (genes).
2. If homosexuality is determined by genes, then a person cannot be held accountable for his or her desires. This is especially true since nothing can be done about the desires.
3. As a natural and immutable phenomenon, homosexuality should not be judged on moral grounds.

Sounds reasonable, doesn't it? I thought so, once, but now it strikes me as naive.

Once upon a time and long ago, I read a rather interesting short story.* In it, someone had discovered that homosexuality was biological and had developed a treatment for it. Unlike the Ex-Gay Groups of today with an acknowledged lack of success this was a Scientifically Proven Literary Device which did, in fact, cause homosexual characters to become heterosexual with no side effects. Though it was never illegal to be homosexual or engage in homosexual activity, the social stigma of having a disorder which could be successfully and painlessly treated led to nearly all homosexuals taking the treatment and becoming heterosexual. Infants were screened as a matter of course and treated whenever they were found to have the gay genes. The story focuses on the last homosexual man in the world, at the deathbed of his lover.

It is a poignant story about love and fidelity, as well as the isolation caused by being stigmatized for who you are when there is a painless way to "treat" the "aberration". It is also, due to the Scientifically Proven Literary Device, fairly optimistic. Most of the homosexuals took the treatment and were able to lead fulfilling lives as heterosexuals. Once the main character died, homosexuality would become nothing more than a disorder for which infants could be successfully treated. It would have gone the way of the dodo.

Let me paint a more likely scenario. Let us say that the so-called "gay gene" is discovered. Likely it will be a suite of genes that reveal a higher likelihood of homosexuality developing (I'm setting aside the idea of a sexual continuum for simplicity's sake). Prenatal screening for the gay genes becomes possible but it's unlikely that there will be any "treatment". What happens? In some cases, nothing. In others, abortions. Don't think it's likely? Consider sex-selective abortion, where female foetuses are aborted because they are female. Or perhaps I should bring up the personal anecdote of one of my lab mates. Her mother was pregnant relatively late in life with my lab mate and wanted to do prenatal testing. The doctor said he would only allow the screening if the mother promised to abort the foetus should the foetus show signs of having Down Syndrome or some other disorder/defect, as though simple information gathering was not a sufficient reason to do prenatal screening. (Her mother refused.)

Now, I am a firm believer in a woman's right to choose whether to bear a child or not and, even if I disagree with her reasons, I don't get to tell her she can't make that choice. The point I'm making is that the choice to abort is not made in a vacuum. It involves making a value judgement on whether a woman wants to bear a child with certain characteristics. Social pressure makes some abortions more sympathetic (or even desirable) than others and, furthermore, there can be a stigmatization of women who choose not to abort foetuses that are somehow "defective" or "wrong".

I don't want to turn this into a discussion of the morality of abortion and choice. I simply want to use it to point out that having a biological component and being natural is no shield to the belief that something or someone is undesirable and generally inferior (for more on this by far more eloquent people, check out FWD/Forward, a blog by feminists with disabilities). The fight for gay rights and dignity can't rest solely on the biological battlefield - it needs to be fought on the grounds that, morally and ethically, it is wrong to treat non-heterosexuals any differently from heterosexuals.

For that, Mr. Spooner, I salute you.

* I no longer remember the name of the story, nor the author. If you happen to recognize it and can send that info to me so I can update this post, you get brownie points.

Welcome to the Rock Show

noreply@blogger.com (K Lam) — Sun, 25 Oct 2009 03:08:00 +0000

According to the internet, genetics is the science of heredity. At first glance, this sounds like we're talking about genes and DNA. In actuality, I think the way that genetics is used outside of strict scientific jargon is much fuzzier. As an example, let's look at Repo! The Genetic Opera.

Repo! the Genetic Opera appeals to my exceptionally geeky side. The basic premise goes like this: in a dystopic future, organ transplants are in high demand due to some unexplained Plot Device that has caused widespread organ failure. Organs are provided by the company GeneCo but when a patient can't pay off their debt, the organ is repossessed by the Repo Man, who cuts out the organ while singing and dancing merrily about his job.

Did I mention this film is a rock opera?

So, if "Repo" refers to the Repo Man and "Opera" refers to the genre of the film, where's the "Genetic"? There's the unexplained Plot Device which may or may not be some kind of genetic defect but it's too underdeveloped to be the main justification for having "Genetic" in the title. The same is true for the mysterious blood condition of Shiloh, the Repo Man's daughter, which was inherited from her mother. Instead, I think "Genetic" refers not to genes per se but to ideas tied to both advancing technology in biology as well as older moral and philosophical thought. Shiloh's illness is a contrived fiction by a tormented father who wants to keep his dead wife alive and safe somehow. The owner of GeneCo, once in love with Shiloh's mother, attempts to steal Shiloh's affections for himself since he believes her to be his spiritual child. His actual children are moral degenerates who vie with each other over control of the GeneCo empire. On a more general level, the advanced technology which allows for rapid and efficient organ transplant has been corrupted so that the rich can pay for excessive and frivolous body modifications while the poor scrap together what money they can to feed their surgical addictions.

In other words, this isn't a film about the science of heredity - it's about the intersection of people, society, and biological technology. I think that's a fascinating place and that's what I want to explore with this blog.

Not quite as heart-poundingly exciting as a rock opera, but it will have to do.