Some Athletes' Genes Help Outwit Doping Test :

The 55 men in a drug doping study in Sweden were normal and healthy. And all agreed, for the sake of science, to be injected with testosterone and then undergo the standard urine test to screen for doping with the hormone.

The results were unambiguous: the test worked for most of the men, showing that they had taken the drug. But 17 of the men tested negative. Their urine seemed fine, with no excess testosterone even though the men clearly had taken the drug.

It was, researchers say, a striking demonstration of a genetic discovery. Those 17 men can build muscles with testosterone, they respond normally to the hormone, but they are missing both copies of a gene used to convert the testosterone into a form that dissolves in urine. The result is that they may be able to take testosterone with impunity.

The gene deletion is especially common in Asian men, notes Jenny Jakobsson Schulze, a molecular geneticist at the Karolinska University Hospital in Stockholm. Dr. Schulze is the first author of the testosterone study, published recently in The Journal of Clinical Endocrinology and Metabolism.

The whole "Asian" angle wouldn't be as important from where I stand if China wasn't intent on becoming an athletic superpower. Specifically, from Doping Test Results Dependent on Genotype of UGT2B17, the Major Enzyme for Testosterone Glucuronidation:

We demonstrated that a deletion polymorphism in the gene coding for UGT2B17...is strongly associated with TG levels in urine...All subjects devoid of the gene had a T/E ratio below 0.4...This polymorphism was considerably more common in a Korean Asian than in a Swedish Caucasian population, with 66.7 and 9.3 % deletion/deletion (del/del) homozygotes respectively.

They don't seem to know what SNP is causing this. If you are curious, you can check out the linkage disequilibrium around UGT2B17.

Labels: Genetics

Public Acceptance of Evolution

Labels: creationism

John Derbyshire has a long column excoriating Ben Stein and the Discovery Institute titled A Blood Libel on Our Civilization:

And there is science, perhaps the greatest of all our achievements, because nowhere else on earth did it appear. China, India, the Muslim world, all had fine cities and systems of law, architecture and painting, poetry and prose, religion and philosophy. None of them ever accomplished what began in northwest Europe in the later 17th century, though: a scientific revolution. Thoughtful men and women came together in learned societies to compare notes on their observations of the natural world, to test their ideas in experiments, and in reasoned argument against the ideas of others, and to publish their results in learned journals. A body of common knowledge gradually accumulated. Patterns were observed, laws discerned and stated.

...

The "intelligent design" hoax is not merely non-science, nor even merely anti-science; it is anti-civilization. It is an appeal to barbarism, to the sensibilities of those Apaches, made by people who lack the imaginative power to know the horrors of true barbarism. (A thing that cannot be said of Darwin. See Chapter X of Voyage of the Beagle.)

Via Talk Islam.

Update: John also rips David Berlinski a new one. Via Quantum Ghosts.

Labels: creationism

For a few weeks I've been mulling over a "theory" about the nature of contemporary fiction. The quotes are because this is a theory in the way that normal people have theories; they don't know much and just make up plausible (to their mind) models that are ultimately grounded in a whole lot of ignorance. I really don't know much here, and I strongly suspect I'm wrong, but I can't help but express an opinion in public though I feel I shouldn't because of my admitted ignorance. To some extent I'm putting this post up to be enlightened by readers who do know a great deal more about letters (e.g., The Man Who is Thursday, who should also resize the little dog so his front page load doesn't go well north of 300 K).

Here's the argument: contemporary mainstream fiction is very different from the storytelling of the deep past because of a demand side shift. Women consume most fiction today, and their tastes differ, on average, from those of men. How do they differ? To be short about it men are into plot, while women are into character. This means that modern literary fiction emphasizes psychological complexity, subtly and finesse. In contrast, male-oriented action adventure or science fiction exhibits a tendency toward flat monochromatic characters and a reliance on interesting events and twists. Over my lifetime I've read a fair amount; but the vast majority of the fiction has been science fiction & fantasy. Many males outgrow this bias, perhaps as they become more psychologically complex and nuanced, but I haven't (though I don't read much fiction in general at this point). I know many other males who are similar; we aren't dumb, and not all of us have Asperger's. We just aren't interested into characterization or character. We are people of exotic ideas, novelty of story arc and exploration of startling landscapes. Contemporary mainstream fiction, high, middlebrow and low, does not usually satisfy these needs.

But ancient fiction; epics, myths, etc., do fulfill these requirements. I didn't seek out fiction in any form before I was 13 or so (I was assigned books in school of course); but I had read Bullfinch's Mythology as well as translations of the Iliad and Gilgamesh. In hindsight I suspect that my interest in these works is due to the fact that they are recognizably High Fantasy. Either they are explicit myths, or, they refer to peoples and places whose lack of banality is due to their distance in time & space (obviously I have never been to the Zagros mountains!). I also have read historical fiction which is sufficiently distant in time, e.g., the whole of Colleen McCullough's Masters of Rome series.

To some extent if you know me in person you can see that I'm not interested in the details of the characters of other human beings. I'm somewhat along the autism spectrum toward Asperger's. I'm not the type to lose myself in a story, and I'm not really interested in most horror films because I have a hard time getting scared or identifying with the characters (I can't forget it's just a movie and the people aren't real). It seems clear to me why I have a hard time being interested in mainstream fiction; not only am I not interested in the characters, but I'm just not like most of the people depicted in terms of their values or personality. I can't "relate," and I'm not interested in "relating."

If you read Isaac Asimov's biography, In Memory Yet Green, I think you get a sense of why his novels depict flat characters. Though Asimov seems to be a gregarious individual, he was very narcissistic and self-involved. I don't get a sense that he was a socially sensitive soul (though he did resent the anti-Semitism he had experienced or slights from strangers). Asimov wrote something of an apologia for science fiction as a genre of ideas, but I think it reflects the set of values which I've expressed above and which many science fiction oriented individuals embody; plots, not people. (if you want every stereotype of science fiction readers confirmed, check out William Sims Bainbridge's Dimensions of Science Fiction, which is based on surveys at science fiction conventions)

For whatever reason Our Kind of People don't become literary critics or arbiters of taste & sophistication. Science fiction & fantasy can never be Great Fiction. If a work of science fiction & fantasy is Great Fiction then by definition it is not science fiction & fantasy. Slaughterhouse-Five, Brave New World and 1984 are not science fiction. Within the science fiction ghetto authors such as Ursula K. Le Guin and Ray Bradbury, who admit or manifest little interest in science as such and emphasize literary values and social messages (especially Le Guin for the latter), are held up as the great authors who are acceptable. In other words, authors for whom psychological exploration just happens to involve a spaceship in the background.

Why does any of this matter? For one, I think that it is somewhat peculiar that many of us find fiction from the past more engaging than popular contemporary works. Aupelius' Golden Ass gets my attention; most contemporary fiction does not. I am arguing here that this is partly due to the fact that in the past those who read copiously were, on average, much more like me than they were like the typical human. Not only were readers by and large men (usually of some means and comfort), but they were often also disproportionately eggheads who were eccentric by their nature. How many elite scholars were there such as Claudius who were not attracted to the public life of politics and do not appear in the annals of history? With the printing press, cheaper paper, and the rise of mass literacy,¹ things changed, the distribution of taste shifted. And so did the distribution of genres.

So am I full of crap?

Addendum: I also think there is a supply-side issue; female authors tend to produce a particular type of work. This is evident within science fiction; female authors are underrepresented in hard science fiction. Here is something from the Wikipedia entry for the Tales of Genji:

The Tale of Genji...is a classic work of Japanese literature attributed to the Japanese noblewoman Murasaki Shikibu in the early eleventh century, around the peak of the Heian Period. It is sometimes called the world's first novel, the first modern novel, or the first novel to still be considered a classic. This issue is a matter of debate. See Stature below.

...

The Genji is also often referred to as "the first novel", though there is considerable debate over this - some of the debate involving whether Genji can even be considered a "novel". Some consider the psychological insight, complexity, and unity of the work to qualify it for "novel" status while simultaneously disqualifying earlier works. Others see these arguments as subjective and unconvincing. Related claims, perhaps in an attempt to sidestep these debates, are that Genji is the "first psychological novel", "the first novel still considered to be a classic", or other more qualified terms. It is, however, difficult to claim that it is the world's first novel without denying the claims of Daphnis and Chloe and Aethiopica in Greek, which author Longus and an unknown sophist respectively wrote, both around the third century, and in Latin, Petronius's Satyricon in the first century and Apuleius's Golden Ass in the second, as well as Kadambari in Sanskrit which author Banabhatta wrote in the seventh century. (The debate exists in Japanese as well, with comparison between the terms monogatari -- "tale" -- and shosetsu -- "novel".)

The first psychological novel? Sounds really boring (though it seems like she makes an attempt at plot, so perhaps I should check this out. I enjoyed Musashi, whose author was influenced by the Tales of Genji).

1 - I am not convinced that even the Athenian democracy was characterized by mass literary. See Ancient Literacy.

Labels: Literature

Over at my other weblog.

Labels: Genetics

A few weeks ago Tyler Cowen mentioned he was reading David W. Anthony's The Horse, the Wheel, and Language: How Bronze-Age Riders from the Eurasian Steppes Shaped the Modern World. I ordered it on Amazon, and it was hanging around the house so I decided to check it out early this evening...I read all 466 pages in one sitting. If you are a GNXP reader interested in archeology, prehistory and Central Asia you have to read this book! I've read In Search of the Indo-Europeans: Language, Archaeology and Myth, The Coming of the Greeks, and Archaeology and Language: The Puzzle of Indo-European Origins, but David W. Anthony really achieved something here which I wasn't prepared for with all due respect to the scholars who authored the aforementioned works. Most readers are aware that I've complained about how happily pig-ignorant of other fields most archaeologists are. Frankly, when I see an academic book I'm curious about, but find out that the author is an archaeologist I get really suspicious. They're good at collecting data, but once the stamps are arranged there seems an extreme reluctance to fire up a real analytic engine.

The author of The Horse, the Wheel, and Language is well aware of these prejudices and refers to them obliquely. He obviously doesn't want to dismiss all of his colleagues as psuedo-scientific quacks, but he admits the general ignorance of archaeologists of fields such historical linguistics which you would think they'd check in on, and alludes to their nearly fanatical adherence to the "Pots not Peoples" paradigm (a reaction to their pre-World War II love affair with migrations). Anthony's interdisciplinary scope is very impressive; he references ideas and conclusions from Albion's Seed and Y: The Descent of Man. Cutting edge research on the evolution of lactose tolerance & the phylogenetics of domesticated cattle are intelligently integrated into the narrative. Nevertheless, the bulk of the text is an extremely dense exposition of archaeological discoveries from sites on the Pontic Steppe since the fall of the Soviet Union. The central argument is that Indo-Europeans emerged from this region between the Dnieper and Volga around 3500 BCE and over the next 1500 years spread in all directions. I won't detail the how or the why, I just finished the book about 15 minutes ago and haven't fully assimilated that much of it, but you can read chapter 1 online.

Note: I don't want to make it seem like this is a breezy popular book, about 2/3 of the material consists of detailed reportage of various sites and analysis of data on pots, cemeteries and seed-husks. Anthony is clearly talking to his fellow scholars, but I think the prose is accessible enough for an interested lay reader as he avoids obscuring jargon. Rather, if you are scared by an endless parade of facts this might not be for you. On the other hand, if your data-gullet is endless, what are you waiting for?

Related: The Inner Asian gap: the Afanasievo breakthrough.

Labels: History

Picking Up Evolution's Beat. Via Kambiz. A representative paper.

A new paper, The Dawn of Human Matrilineal Diversity, is out in AJHG. I read too much John Hawks to really be all that excited about mtDNA based studies, and this paper is Mitochondrial Eve to the n^th power. But...I do think it is indicative of a trend which suggests a rollback from the most extreme Out of Africa scenarios; i.e., that one band somewhere in Eastern Africa arose ~100,000 years ago and expanded demographically so that they were the exclusive ancestors of all human beings.¹ The introgression story is one angle; but the likelihood of preexistent population substructure within Africa itself is another. If you don't read the paper (which is Open Access), just check out Figure 1 and the map. Breathless description of the study over at ScienceDaily of course....

Related: Kambiz comments in more detail.

1 - Some of this was more about public perception than reality; just like the one mtDNA ancestor was conflated with one female ancestor (the same trick of course applied to the NRY).

Labels: Evolution

One of the "debates" currently occupying evolutionary biology is whether evolution occurs primarily via changes in protein-coding sequence or via changes in gene regulation (apparently it's become so heated that battles between the two camps are now fought through t-shirts).

As understanding of the genetics of adaptation advances, this debate will likely fade away--a priori, it's easy to make the case for either, and well-studied individual examples are showing that, as one might expect, evolution isn't particularly dogmatic about the sources of variation it works with.

It's these case studies that are most interesting--take, for example, a recent study on the adaptation of Arabidopsis halleri to the heavy-metal-polluted soils it now occupies. This is quite a nice example of evolution via gene regulation--the authors map the ability to tolerate heavy metals to a particular candidate gene, then identify both a change in copy number as well as changes in the promoter region of the gene that lead to high levels of expression. To complete the story, they then pop this highly expressing version of the gene back into A. thaliana (the model organism) and show they're able to recreate the crucial aspects of the adaptation in that species.

Labels: Evolution, Genetics

Statistical Modeling, Causal Inference, and Social Science asks where asks where all the Smiths have gone:

Sam Roberts writes,

In 1984, according to the Social Security Administration, nearly 3.4 million Smiths lived in the United States. In 1990, the census counted 2.5 million. By 2000, the Smith population had declined to fewer than 2.4 million.

Where did all the Smiths go from 1984 to 1990? I can believe it flatlined after 1990, but it's hard to believe that the count could have changed so much in 6 years.

Perhaps it's the difference between the SSA and Census methods of counting

Here's another explanation, it's the inverse of the phenomenon of those claiming Native American ancestry in the United States doubling in 10 years. Many Smiths were at one point Schmidts, who knows if some of them didn't revert now that WASP surnames aren't as value-added? I strongly suspect that the number of ethnic whites in the USA is overstated because those with mixed-ancestry emphasize the most non-traditional quanta of their heritage. That means if someone is 1/4 German & 3/4 English they might declare their ethnicity as German. I'll probably have to look up some social science on this question at some point....

Note: the rank of Schmidt increased in terms of rank by 33 from 1990 to 2000.

Update: I took a bunch of German names and their English or Anglicized variants and compared their ranks between 1990 and 2000. I'm sure that the trend you see is the combined result of the decrease in proportion of those with very common Anglo names because of the decline of the non-Hispanic white fraction as well as a moderate stream of new German immigrants. But who knows?

Smith	-	Schmidt	+33
Shepard	-37	Shafer	+254
Baker	-1	Becker	+74
Miller	+1	Muller	+147
Taylor	-3	Schneider	+57
Hill	+8	Berg	+122
Miner	-202	Bergman	+2
Brown	+1	Braun	+176
Dyer	-111	Farber	+1090
Finch	-115	Fink	+183
Fox	+19	Fuchs	+613
Duke	-78	Herzog	-341
Hunter	-23	Jaeger	+631
Buck	+18	Hirsch	+241
Young	-3	Jung	+840
Hoover	+39	Huber	+126
Cook	-4	Koch	+79
King	-5	Koenig	+366
Cooper	-2	Kruger	+191
Long	-	Lang	+43
Mason	-14	Maurer	+160
Butcher	+68	Metzger	+424
Piper	-239	Pfeiffer	+372
Knight	-44	Ritter	+161
Barber	-41	Scherer	+1029
Black	-11	Schwartz	+102
Roper	-72	Seiler	+137
Weaver	+11	Weber	+71
White	-6	Weiss	+131

Update II: Proportion of German Americans dropping faster than English Americans?

Update III: Took some Census 2000 data and produced this....

Ancestry	First Ancestry	Second Ancestry	Total	Ratio of First to Second Ancestry
German	30165672	12674039	42839711	2.38
Irish	19279211	11245588	30524799	1.71
English	16623938	7885754	24509692	2.11
Italian	12836020	2799547	15635567	4.59
French	4870907	3436659	8307566	1.42
Scottish	3142893	1747688	4890581	1.8
Dutch	2552688	1986681	4539369	1.28
Norwegian	3241637	1236088	4477725	2.62
Scotch-Irish	3283065	1036167	4319232	3.17
Swedish	2436825	1561478	3998303	1.56
Welsh	886139	867655	1753794	1.02
Danish	855797	574927	1430724	1.49
Portuguese	913859	259832	1173691	3.52
Greek	942723	210315	1153038	4.48
British	828089	207044	1035133	4
Swiss	535408	374661	910069	1.43
Austrian	433292	297044	730336	1.46
Finnish	435446	188073	623519	2.32
Scandinavian	308051	117048	425099	2.63
Belgian	217524	130754	348278	1.66
Sicilian	68290	16885	85175	4.04
Celtic	53438	12200	65638	4.38
British Isles	42137	7941	50078	5.31
Luxemburger	26378	18761	45139	1.41
Icelander	30388	12328	42716	2.46
Basque	32121	9690	41811	3.31

I think the ratio of First to Second ancestry is probably a pretty good sense out admixture/outmarriage rates. Look at the Welsh; not very distinct from other British Isles groups and far less numerous, ergo lots of second ancestry.

Update IV: Median age for people of English ancestry is 44. For German it is 37. Same with Irish. What's up with that?

Labels: culture

The caption:

The first column shows the theoretical expected PC maps for a class of models in which genetic similarity decays with geographic distance (see text for details). The second column shows PC maps for population genetic data simulated with no range expansions, but constant homogeneous migration rate, in a two-dimensional habitat. The columns marked Asia, Europe and Africa are redrawn from the originals of ref. 3 [this reference is to Cavalli-Sforza's The History and Geography of Human Genes]. Each map is marked by which PC it represents. The order of maps in each of the last three columns was chosen to correspond with the shapes in the first two columns.

What does this mean? The authors say it best in the abstract:

Nearly 30 years ago, Cavalli-Sforza et al. pioneered the use of principal component analysis (PCA) in population genetics and used PCA to produce maps summarizing human genetic variation across continental regions. They interpreted gradient and wave patterns in these maps as signatures of specific migration events. These interpretations have been controversial, but influential, and the use of PCA has become widespread in analysis of population genetics data. However, the behavior of PCA for genetic data showing continuous spatial variation, such as might exist within human continental groups, has been less well characterized. Here, we find that gradients and waves observed in Cavalli-Sforza et al.'s maps resemble sinusoidal mathematical artifacts that arise generally when PCA is applied to spatial data, implying that the patterns do not necessarily reflect specific migration events.

Labels: Population genetics

Clark has a post pointing to the obvious parallels between the practices of the Fundamentalist Church of Jesus Christ of Latter Day Saints and those of West African immigrants. The "problem" with the FLDS situation is pretty clear; they're WASPs with weird folkways. Of course the reaction to the FLDS is simply a retread of what happened with the original Mormons, a culturally heterodox group whose primary following was among the lower and lower middle class of Greater New England.¹ I had friends in high school who were from the old Mormon stock whose ancestors had been driven west; many of the remembrances passed down through the generations resembled those of the Trail of Tears. My friends were proud & patriotic Americans, but I was surprised that on a deep level they seem to have never forgotten the persecution which Mormons experienced from the American government and the people which it claimed to represent.

The "problem" with the original Mormon church, and the FDLS today, is that we aren't living in a land of black & white, where good and evil are clear and distinct. In some ways the early Mormons were an admirable folk, picking themselves up by their own bootstraps and forging a new religion in the wilderness of the American continent. But they also manifested hostility toward outgroups and an exclusionary tendency which ill-suited them in their interaction with other Americans, "gentiles" as they would call them. The history of the Mormons from their original emigration down to the banning of polygyny was one of interminable conflict with the American republic, the Utah territory was defined by the clash between a Mormon theocracy and the occupational government of the United States. This enmity was only resolved by the Mormon rejection of polygyny.


This episode showed that the tolerance of the American polity had its limits. Though multiculturalism is a relatively new concept in terms of its elaboration, the United States of the 19th century was shockingly diverse when it came to religious pluralism. The Mormons themselves were an outgrowth of the Second Great Awakening, which transformed the American South into the domain of Baptists and produced many of the mainstream denominations which are still on the scene today. Joseph Smith's cult is the most exotic outlier, but it was not entirely atypical. Smith's sin was not to push Protestantism into a new direction, it was the fact that he dragged the Mormon church into a landscape which transgressed against the bourgeois norms at the heart of American society (this occurred with other religious-social groups which emerged out of the Second Great Awakening, but only the Mormons remain).

The emblematic violation of those norms was of course plural marriage, polygyny. I don't think that plural marriage is wrong like murder is wrong, but the social dynamics which emerge from its ubiquitous practice among the FLDS are well known, and I am skeptical that the practice is conducive to the perpetuation of a bourgeois republic. Even within the Muslim world modernizers are very critical of polygyny because of the familial destabilization it portends. In a world where time is finite one can make quick back of the envelope inferences about the effect upon parental inputs in a situation where one man fathers dozens of children with multiple wives. Though there are very specific principled arguments one can against polygyny, I suspect that the consequentialist ones are at the heart of the relatively universal objection to the practice from most Americans.

The FLDS situation gets to the heart of a broader problem in any polity, and that is one of diversity of values. As WASPs without the race card to bail them out the members of the FLDS find themselves facing the reality of prejudice & discrimination at the hands of the majority. On pure moralistic grounds I think one can point to the ubiquity of debauched polyamory in much of American society, and low "paternity certainty." Why this fixaton on the FLDS's practices? Aside from the formalization of a routine of statutory rape encouraged by Warren Jeffs, I suspect a bigger issue is that the FLDS legitimizes & solemnizes practices Americans want to keep marginalized and sinful (for lack of a better word). Most Americans are regularly bombarded with the message that prejudice & discrimination are bad, but the reality is that we engage in these activities every single day of our lives. Our rejection of polygyny brings into stark relief the persistence of shibboleths and unspoken norms. The non-ethnic whiteness of Fundamentalist Mormons results in our disgust not being buffered by race guilt or discounting of the practitioners of exotic behaviors as marginally human. The members of the FLDS are "All American" in their stock, so their practices are more repulsive than they would otherwise be. They are apostates from the bourgeois consensus.

And consensus is vitally important, no matter how much we wish to emphasize the value of public debate and difference. Winnifred Sullivan's book The Impossibility of Religious Freedom elucidated the charade that a world without prejudice & discrimination truly is. In Catholicism & American Freedom John T. McGreevy documents how American Catholics became part of the mainstream in large part due to their assimilation of American values and folkways. In other words, Catholicism became acceptable when it became Protestant, the apotheosis of which was John F. Kennedy.² Because religion is so important to people we treat it differently; Americans receive exemptions and dispensations from civil expectations if their religious obligations or taboos contradict mainstream norms. But these exemptions can only go so far, and they are extended only toward particular groups who have received the acclaim necessary for public recognition.

The treatment meted out to the FLDS illustrates the limits of the tolerance of acts between consenting adults, that the circle of diversity is not without boundaries. The historical record also shows that the tolerance extended toward numerous factions such Catholics and Jews was in large part a reflection of the fact that both of these groups subsumed themselves into the set of expectations which were normal within American Protestantism.³ For sects where the numbers are smaller, such as the Amish, heterodoxy is accepted because their impact is so marginal and their custom are in the generality inoffensive or quaint. In the past the American society admitted the reality of these boundaries and the general outline of our circle of tolerance; today we are somewhat in denial, and the schizophrenic reaction to something like the FLDS controversy reflects the clash between our deep-rooted values and our notional avowal of universal multiculturalism.

Related: Jake Young blogs the economic benefits of monogamy.

1 - Greater New England included much of northern Ohio, for example.

2 - I obviously don't mean that American Catholicism is in schism from the Roman Church. Rather, in terms of the conception of their relationship to their religion of choice American Catholics bring American Protestant presuppositions. This was clear even during the early 19th century, but the massive influx of European Catholic immigrants de-Americanized the church by around 1850 and brought to the fore "Old World" values and and expectations in terms of how the church would relate to the state. The result was decades of conflict which only abated when the children of the immigrants became numerically dominant and brought their own American sensibilites to the table. Simultaneously with this demographic shift the international Roman Catholic Church was shifting to a more "Americanist" perspective, culminating in Vatican II. The point is that the United States culture didn't really compromise with the Catholic Church, the church was transformed until it became acceptable.

3 - Note the popularity of non-"Orthodox" Judaism in the United States.

Labels: culture

A common SNP of MCPH1 is associated with cranial volume variation in Chinese population:

Microcephaly (MCPH) genes are informative in understanding the genetics and evolution of human brain volume. MCPH1 and abnormal spindle-like MCPH associated (ASPM) are the two known MCPH causing genes that were suggested undergone recent positive selection in human populations. However, previous studies focusing only on the two tag single nucleotide polymorphisms(SNPs) of MCPH1 and ASPM failed to detect any correlation between gene polymorphisms and variations of brain volume and cognitive abilities. We conducted an association study on eight common SNPs of MCPH1 and ASPM in a Chinese population of 867 unrelated individuals. We demonstrate that a non-synonymous SNP (rs1057090, V761A in BRCA1 C-terminus (BRCT) domain) of MCPH1 other than the two known tag SNPs is significantly associated with cranial volume in Chinese males. The haplotype analysis confirmed the association of rs1057090 with cranial volume, and the homozygote males containing the derived alleles of rs1057090 have larger cranial volumes compared with those containing the ancestral alleles. No recent selection signal can be detected on this SNP, suggesting that the brain volume variation in human populations is likely neutral or under very weak selection in recent human history.

They used EHH & iHS. Also, they suggest that the derived form of rs1057090 is very ancient (the SNP has a very small window of linkage disequilibrium around it).

Related: This is Bruce Lahn's brain on ASPM and MCPH1, Did Modern Humans Get a Brain Gene from Neandertals?, Microcephalin & ASPM and Selection "controversy".

Labels: Genetics

The discussion continues in regards to the relationship of various West Eurasian and North African groups (i.e., Europeans, North Africans and Near Easterners). There have been several papers published within the last few years which shed some light on these questions. We've blogged them before, and I don't think that they radically alter what you might find in History and Geography of Human Genes, but I thought I'd point to them again, with a special focus on figures of note.

European Population Substructure: Clustering of Northern and Southern Populations. Figure 4 B:


Analysis and Application of European Genetic Substructure Using 300 K SNP Information, Figure 1 B & D:


Discerning the Ancestry of European Americans in Genetic Association Studies, Figure 3 A:


Analysis of genetic variation in Ashkenazi Jews by high density SNP genotyping, Figure 9:


Since these papers are all Open Access there's really no excuse to not read them (at least the "Discussion" sections). I hope people won't go around looking for charts to "prove" whatever pet hypothesis they want to promote, the population-level classifications we generate often have only an approximate relationship to the multi-dimensional shape of human genetic variation at the finer-grained level. Note that some of these principal component charts really don't have that many individuals typed, and you may wonder about the representativeness of the samples of their putative national populations. Though these are important points, I do think we need to be cautious about our expectations in regards to the sort information we're going to extract on the margins as the N increases and the individuals typed come from every region of a nation. I suspect we'll get more oddities like the Etruscans as isolated or peculiar populations are included in these samples, and the exceptions to the broad patterns tell us a lot about the details of human history. But, I doubt we'll overturn the general shape of the relationships and clinal gradients we see here.

Addendum: I somewhat played down the future surprises that these sorts of fine grained analyses might have for us...but I do want to note that the studies will continue. That's because they aren't done for the purposes of elucidating human genetic history as such, rather, the primary rationale is to highlight substructure which might be relevant when attempting to ascertain disease relevant alleles. In the medical context then there may be significant returns on the investment here which I don't want to underestimate. If, for example, a particular drug's efficacy within the African American population in the United States is directly proportional to the makeup of one's ancestry then identifying ancestry-informative markers is very useful.

Update: Measuring European Population Stratification with Microarray Genotype Data, Figure 1 A:

Labels: Genetics

Greg's post about SNPs, Jews and evolutionary genetic parameters has been getting a lot of play around the blogs & forums. Most of it seems to be due to the persistent interest in the genetic relationship of Ashkenazi Jews to other European populations. This makes sense, since the 19th century the question of how the "Jewish race" relates to European gentiles has had some sociopolitical relevance.... But a commenter at Steve's blog pointed out that Bauchet et al. from last year had a PC chart which included Armenians, who are I think a good proxy for northern Middle Eastern populations in general. One interesting result from surveys of Y chromosomal lineages is the finding that Jews may have more affinities with northern Levantine & Anatolian Middle Eastern populations than with southern Levantine and Arabian ones. The non-trivial female mediated input of Sub-Saharan ancestry into many Arab populations since the rise of Islam is far less evident in non-Arab Muslim populations (Kurds, Persians and Turks) as well as Middle Eastern Jews, and obviously Ashkenazi ones. But another point is that recent work suggests that the impact of historical events (e.g., the Arab conquest) might have been more demographically significant than we had previously assumed, and so Jewish affinity with northern Middle Eastern populations may reflect that these groups have been less affected by exogenous genetic inputs within the last 2,000 years.

Caution about the sample sizes of course (though I assume within the next year we'll have much better data to go off of), but something to include into your list of priors when making phylogenetic background assumptions.

Note: I added geographic labels to the PC chart for clarification.

Update: Steve has another post up:

On the first two axes, Ashkenazi Jews are rather close to "Europeans" and "Russians." They are similar to Yemenites (from Southern Arabian peninsula) on the first axis, but not on the second. And they are similar to Samaritans (who currently subsist on two hilltops in Israel), good, bad or indifferent, on the second axis but not on the first. They are fairly similar to the Druze (of Lebanon and Israel) on the first two axes, but not on the third.

...

So, Ashkenazis look pretty European on this chart compared to a few Middle Eastern groups. But, as the recent graph showed, genetics has progressed to the point where Ashkenazis (at least those with four Ashkenazi grandparents) can now be reliably distinguished from other Europeans.

The Samaritans are cousins of the Jews. But:

In the past, the Samaritans are believed to have numbered several hundred thousand, but persecution and assimilation have reduced their numbers drastically. In 1919, an illustrated National Geographic report on the community stated that their numbers were less than 150.

Like the Kalash or Sardinians the Samaritans are going to be weird outliers because of their demographic history. Inbreeding and no gene flow in for that long will do that to