Chromosomal abnormalities..

I finished Peter Jensen’s book, which I also mentioned in the previous post, this morning, and I decided to add a few comments and links to articles covering stuff he also covers in his book. I liked the book and gave it 3 stars on goodreads. It’s old – from 1998 – so a lot of stuff has happened since then in this field (e.g. ‘new’ genetic diseases, such as 17q21.31 microdeletion syndrome, have been ‘discovered’ – though I should caution here that according to Jensen a distinction is to be made between ‘chromosomal abnormalities’ and ‘genetic diseases’; unlike many genetic disorders, chromosomal abnormalities involve mutations which are large enough to be seen using an ordinary light microscope). However my working assumption has been that most of the stuff covered in the book is unlikely to have changed much; how a chromosomal abnormality affects the individuals who have it doesn’t change much from one decade to another, even though improvements in medical technology may have improved outcomes for some specific diseases.

Some links to stuff he talks about in the book, in no specific order: Chromosome abnormality (I should add that pretty much every link in that article is to an article on something which is also covered in the book), Aneuploidy, Robertsonian translocation, Klinefelter syndrome, Turner Syndrome, Williams Syndrome, Down Syndrome, Patau syndrome, Fragile X syndrome, Angelman Syndrome, Prader-Willi syndrome, Barr body, Non-disjunction, Amniocentesis, Trisomy 8, FMR1.

A few general remarks: It should be noted that autosomal chromosomal abnormalities are usually more severe than sex-linked chromosomal abnormalities. More than 95% of chromosomal abnormalities result in spontaneous abortion, and 60% of early spontaneous abortions (within the first trimester) are due to chromosomal abnormalities. Monosomies (including partial ones) tend to have more severe consequences than do trisomies. Even though people tend to think that way about genetic diseases not all chromosomal abnormalities are best thought of as inhabiting a binary event space (either you have it or you don’t); some of them display to a significant extent a dose–response relationship (see e.g. the articles on the FMR1 gene & Fragile X syndrome). As should be obvious from the number of associated abortions, many of the chromosomal abnormalities (particularly the autosomal ones) lead to really horrible outcomes: Among Pataus Syndrome sufferers less than 40% survive past [remember: 1998 numbers] one week after birth, and only 4,5% survive past 6 months [according to wikipedia's article on the topic, "More than 80% of children with Patau syndrome die within the first year of life" - so mortality is still very high]; when it comes to Edward’s syndrome likewise approximately 60% died within a week, and around 5% were still alive after a year back then – and this is just considering the variable survival, not stuff like blindness, polydactyli, organ malformation (brain, heart, kidneys, …), deafness, etc., etc., which are also very often present in people with these disorders…

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Incidentally I read most of Carpe Jugulum today, but I won’t blog that one until tomorrow.

Stuff (updated)

(After Ed Yong published his latest post, I decided to add a couple of links – Monday, 10 a.m.)

i. Introduction to Evolutionary Biology (TalkOrigins)

I read this yesterday, I’m sure some of you will find it to be useful. Some quotes:

“Populations evolve. [evolution: a change in the gene pool] In order to understand evolution, it is necessary to view populations as a collection of individuals, each harboring a different set of traits. A single organism is never typical of an entire population unless there is no variation within that population. Individual organisms do not evolve, they retain the same genes throughout their life. When a population is evolving, the ratio of different genetic types is changing — each individual organism within a population does not change. For example, in the previous example, the frequency of black moths increased; the moths did not turn from light to gray to dark in concert. The process of evolution can be summarized in three sentences: Genes mutate. [gene: a hereditary unit] Individuals are selected. Populations evolve.

Evolution can be divided into microevolution and macroevolution. The kind of evolution documented above is microevolution. Larger changes, such as when a new species is formed, are called macroevolution. Some biologists feel the mechanisms of macroevolution are different from those of microevolutionary change. Others think the distinction between the two is arbitrary — macroevolution is cumulative microevolution.

The word evolution has a variety of meanings. The fact that all organisms are linked via descent to a common ancestor is often called evolution. The theory of how the first living organisms appeared is often called evolution. This should be called abiogenesis. And frequently, people use the word evolution when they really mean natural selection — one of the many mechanisms of evolution. [...]

Evolution can occur without morphological change; and morphological change can occur without evolution. Humans are larger now than in the recent past, a result of better diet and medicine. Phenotypic changes, like this, induced solely by changes in environment do not count as evolution because they are not heritable; in other words the change is not passed on to the organism’s offspring. [...]

Evolution is not progress. Populations simply adapt to their current surroundings. They do not necessarily become better in any absolute sense over time. A trait or strategy that is successful at one time may be unsuccessful at another.” [...]

Organisms are not passive targets of their environment. Each species modifies its own environment. At the least, organisms remove nutrients from and add waste to their surroundings. Often, waste products benefit other species. Animal dung is fertilizer for plants. Conversely, the oxygen we breathe is a waste product of plants. Species do not simply change to fit their environment; they modify their environment to suit them as well. [...]

Natural selection may not lead a population to have the optimal set of traits. In any population, there would be a certain combination of possible alleles that would produce the optimal set of traits (the global optimum); but there are other sets of alleles that would yield a population almost as adapted (local optima). Transition from a local optimum to the global optimum may be hindered or forbidden because the population would have to pass through less adaptive states to make the transition. Natural selection only works to bring populations to the nearest optimal point. This idea is Sewall Wright’s adaptive landscape. This is one of the most influential models that shape how evolutionary biologists view evolution. [...]

Sexual selection is natural selection operating on factors that contribute to an organism’s mating success. Traits that are a liability to survival can evolve when the sexual attractiveness of a trait outweighs the liability incurred for survival. A male who lives a short time, but produces many offspring is much more successful than a long lived one that produces few. The former’s genes will eventually dominate the gene pool of his species. In many species, especially polygynous species where only a few males monopolize all the females, sexual selection has caused pronounced sexual dimorphism. In these species males compete against other males for mates. The competition can be either direct or mediated by female choice. In species where females choose, males compete by displaying striking phenotypic characteristics and/or performing elaborate courtship behaviors. The females then mate with the males that most interest them, usually the ones with the most outlandish displays. There are many competing theories as to why females are attracted to these displays.” (In humans, females choose so this could be construed as another bit of dating advice to add to this post…) [...]

“Most mutations that have any phenotypic effect are deleterious. Mutations that result in amino acid substitutions can change the shape of a protein, potentially changing or eliminating its function. This can lead to inadequacies in biochemical pathways or interfere with the process of development. Organisms are sufficiently integrated that most random changes will not produce a fitness benefit. Only a very small percentage of mutations are beneficial.”

There’s a lot more at the link. Not all of it belongs in the ‘all people who know anything about evolutionary biology would agree on this 100 percent’-category [one example: "Genes are not the unit of selection (because their success depends on the organism's other genes as well); neither are groups of organisms a unit of selection. There are some exceptions to this "rule," but it is a good generalization." - not everybody 'in the field' would agree with that], but most of it is relatively incontestable and it covers a lot of ground; a huge number of key concepts are explained and elaborated upon here. Read it, but don’t start reading it before you’re in a situation where you have a decent amount of time to spare. No matter how well-read you are, unless you’ve actually read this piece before odds are you’ll not know everything which is covered here – for instance, you probably didn’t know that “over half of all named species are insects. One third of this number are beetles.” I know I didn’t. The article was written a while ago, so I decided to check up on the data – here’s what wikipedia has to say about the matter today: “Even though the true dimensions of species diversity remain uncertain, estimates are ranging from 1.4 to 1.8 million species. [...] About 850,000–1,000,000 of all described species are insects.” I should probably point out that even though it’s written in a manner-of-fact like way all the way through, he incidentally doesn’t exactly beat about the bush at the end:

“Scientific creationism is 100% crap. So-called “scientific” creationists do not base their objections on scientific reasoning or data. Their ideas are based on religious dogma, and their approach is simply to attack evolution. The types of arguments they use fall into several categories: distortions of scientific principles ( the second law of thermodynamics argument), straw man versions of evolution (the “too improbable to evolve by chance” argument), dishonest selective use of data (the declining speed of light argument) appeals to emotion or wishful thinking (“I don’t want to be related to an ape”), appeals to personal incredulity (“I don’t see how this could have evolved”), dishonestly quoting scientists out of context (Darwin’s comments on the evolution of the eye) and simply fabricating data to suit their arguments (Gish’s “bullfrog proteins”).

Most importantly, scientific creationists do not have a testable, scientific theory to replace evolution with. Even if evolution turned out to be wrong, it would simply be replaced by another scientific theory.”

As can also be inferred from the links at the end, this is not the only post of its kind at TalkOrigins. Go have a look if you’re even remotely interested!

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ii. Two figures:

(link).

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iii. How far do Danes commute to go to work? Answer: It varies.

The table includes the Danish municipalities with the ten highest and lowest average commuting distances. The distances given in the table are the distances between the homes of the commuters and their workplaces, not the distances travelled on an average day (which would be twice that number). Local or regional wage differentials and corresponding differences in opportunity cost of time definitely plays a role here. Note that ‘distance travelled’ is not necessarily a good proxy for ‘time spent commuting’, especially not when comparing the commutes of people living in urban areas with those of people living in rural areas (ceteris paribus, d(commuting time)/d(pop-density)>0). The numbers are from this new publication by Statistics Denmark, which also included this map of the gender differences across the country (yellow: the average male commute is less than 6 kilometers longer than the average female commute, etc. The darker, the bigger the difference between the genders..):

The national average commuting distance to work is ~20 km (19.7). The male average is 23.4 km, the female average is 15.9 km.

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iv. This should all be known stuff to you guys, but in case it’s not:

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v. A number: 27.5% of all inmates in Danish prisons are foreign citizens (article in Danish here). Foreign citizens make up about 7,7% of the population. If you look closer, I’m positive both that you’ll find huge variation across countries, and that you’ll also find that some immigrant groups are significantly less likely to commit crimes than are people with Danish citizenship.

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vi. The Long, Fake Life of J.S. Dirr. An internet hoax that survived for 11 years, from the very beginning of social medias almost to the present day. Interesting.

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vii. Why You Can’t Kill a Mosquito with a Raindrop. Add this one to the list of questions I had never even thought about asking. Fascinating stuff, a few quotes:

“the consequence of getting hit by a raindrop depends on what part of the mosquito’s body takes the blow. Since the insects are so lanky, 75% of hits happen on the legs or wings. This can throw a mosquito into a brief tumble or even a barrel roll, but it recovers without much trouble.

Direct hits to mosquitos’ bodies are a different kind of carnival ride. The speeding raindrops glom onto the insects and propel them downward. Mosquitos captured on camera sometimes fell as far as 20 body lengths while being pushed by a raindrop. For a human, that would be a 12-story drop and a quick ending to the story. But mosquitos are able to pull away sideways from the raindrops and continue on their way, unharmed.

The only danger seems to come if mosquitos are flying close to the ground when they’re hit, leaving themselves too little time to escape. The authors note that one unlucky bug was driven into a puddle and “ultimately perished.” [...]

When the heavy drop hits the airy mosquito, it’s almost like hitting nothing at all. And this, the researchers found, is what keeps the mosquitos alive. By offering barely any resistance, a mosquito minimize the force of the collision. The raindrop doesn’t even splatter when it hits. [...]

Humans being hurled downward generally black out around 2 or 3 G’s. But a mosquito suddenly driven toward the ground by a raindrop experiences an acceleration of 100 to 300 G’s. The authors note that “insects struck by rain may achieve the highest survivable accelerations in the animal kingdom.”"

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viii. TV Tropes tips for writers.

The genetics of type 1 diabetes

There’s this question I’ve been asked many times: “Type 1 diabetes? Is that genetic?”

I was asked it again a couple of weeks ago and it caught me off-guard so I don’t think I was being quite as precise as I’d have liked to be – by having now written this post, I hope that I’ll do better next time (oh yes, there’ll be a next time…). Before going any further I should probably note here that even though I don’t know much about genetics, I estimate that I do know (/significantly?) more than most people who would choose to ask such a question: Having been exposed to stuff like Khan Academy, Razib Khan’s blog, Wikipedia (way too much to link to here), Russell, Dawkins and Majerus for instance means that I know the difference between a recessive allele and a linkage disequilibrium. It also means that I’m very inclined to answer a question like that one by asking another question: “What do you mean by ‘is it genetic?’” Genetics is complex stuff and there are many kinds of genetic disorders. I’ve tended to assume that people who ask do so more because of the implied blame-angle inherent in the question (‘it’s not your own fault you’re sick, right?’) than because of their deep interest in the disease etiology of type 1 diabetes – but I shouldn’t let that affect the way I respond, given that a reasonably clear answer to the question (…I assume they think they are asking) exists today (wikipedia):

“Type 1 diabetes is partly inherited and then triggered by certain infections, with some evidence pointing at Coxsackie B4 virus. There is a genetic element in individual susceptibility to some of these triggers which has been traced to particular HLA genotypes (i.e., the genetic “self” identifiers relied upon by the immune system). However, even in those who have inherited the susceptibility, type 1 diabetes mellitus seems to require an environmental trigger.”

So the simple version is that ‘genetics’ increases disease susceptibility and an infection then triggers the disease process. Here’s the abstract of a new study, Genetics of Type 1 Diabetes, by Steck and Rewers, providing a little more detail:

“BACKGROUND: Type 1 diabetes, a multifactorial disease with a strong genetic component, is caused by the autoimmune destruction of pancreatic β cells. The major susceptibility locus maps to the HLA class II genes at 6p21, although more than 40 non-HLA susceptibility gene markers have been confirmed.

CONTENT: Although HLA class II alleles account for up to 30%–50% of genetic type 1 diabetes risk, multiple non-MHC loci contribute to disease risk with smaller effects. These include the insulin, PTPN22, CTLA4, IL2RA, IFIH1, and other recently discovered loci. Genomewide association studies performed with high-density single-nucleotide–polymorphism genotyping platforms have provided evidence for a number of novel loci, although fine mapping and characterization of these new regions remain to be performed.

Children born with the high-risk genotype HLADR3/4-DQ8 comprise almost 50% of children who develop antiislet autoimmunity by the age of 5 years. Genetic risk for type 1 diabetes can be further stratified by selection of children with susceptible genotypes at other diabetes genes, by selection of children with a multiple family history of diabetes, and/or by selection of relatives that are HLA identical to the proband.

SUMMARY: Children with the HLA-risk genotypes DR3/4-DQ8 or DR4/DR4 who have a family history of type 1 diabetes have more than a 1 in 5 risk for developing islet autoantibodies during childhood, and children with the same HLA-risk genotype but no family history have approximately a 1 in 20 risk. Determining extreme genetic risk is a prerequisite for the implementation of primary prevention trials, which are now underway for relatives of individuals with type 1 diabetes.”

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“Children born with the high-risk genotype HLADR3/4-DQ8 comprise almost 50% of children who develop antiislet autoimmunity by the age of 5 years” – in plain English, this means that almost half of all type 1 diabetics who show disease development before the age of 5 have this specific high-risk genotype. Note also how complex this disease is in terms of the genetics – ‘more than 40 non-HLA susceptibility gene markers have been confirmed’. Maybe some of them are just flukes due to p-value hunting, but that’s a lot of genes impacting disease risk.

Steno has some stuff in Danish here if people are interested. According to their numbers, if the mother has type 1 diabetes there’s a 2% risk that her child will have the disease. If the father has the disease the risk is 5%. Lægehåndbogen states that for monozygotic twins, if one twin develops the disease the risk that the other twin will also get it is 50%.

A Natural History of Ourselves (1)

By Hannah Holmes.

“Whenever biologists discover a new animal it’s their custom to crank the creature through a factual sausage grinder, producing tidy links of information. With academic detachment they tabulate the number of legs and teeth, note food preferences, and characterize habits of reproduction. [...] But I’ve never encountered a full description of the two-legged ape. We Homo sapiens, so eager to describe the rest of the world, have been chary about committing our own natural history to paper.
This seems unfortunate. For one thing, it reinforces the notion that we’re not normal animals. It lends the impression that we’re too wonderful to summarize; that although the giraffe can be corralled in paragraphs, the human cannot. That’s unfair to other species. On the flip side, it suggests we’re misfits, as animals go. It lends the impression that we’re not worthy to take our place beside the gemsbok and the gorilla; that we are excluded from the brotherhood of mammals. This is unfair to my species.
It also seems unnecessarily dour. What could be more fun than describing the human, after all?”

From the introduction. The book is quite funny and you learn a lot of new stuff. That said, it also gets a few things wrong, and I’ve gotten a bit annoyed a couple of times because she keeps repeating a common mistake people make when dealing with evolutionary bioloy: Assuming traits or behavioural strategies which are widespread today must necessarily have been advantageous in the past. It’s an easy mistake to make, but it’s the wrong way to think about these things: A general rule of thumb is rather that all it takes for a given trait to persist over time is for the trait to not be so costly as to give rise to a significant evolutionary disadvantage. Traits that impact the number of offspring in a positive way will generally spread (if certain other conditions are met), but neutral traits and adaptions can easily persist over time as well. Harmful traits are the only ones that generally have a hard time making it over time, and if you see the trait in individuals today and it’s been around for a while, the trait probably isn’t all that harmful – at least in terms of offspring impact, likelihood of mating ect.. She makes the mistake both when talking about traits more or less directly linked to genetics (‘color blindness has persisted because: “it gave hunters an advantage in spotting khaki-colored animals in the khaki-colored grasslands of human prehistory”) and also when talking about purely cultural adaptions (according to her, the new HIV study showing that circumcision reduces infection risk (slightly) might indirectly be part of the explanation why people thousands of years ago decided to cut off parts of the penis of their male children and keep doing it – “If circumcision does indeed reduce the risk of males contracting fatal diseases, that could well have kicked “cultural evolution” into gear long, long ago: Those groups of humans who practiced the cultural behavior would enjoy better survival rates.” My response would go somewhere along these lines: Sorry for asking, but what about wound infection risk 2000+ years ago? Risk of botched circumcision reducing number of offspring to 0? And just how big would the impact on transmission rates of i.e. sexually transmitted diseases have to be to actually offset these costs (the effect size in the HIV study was quite small)? Also, lots of fatal diseases one might come up with, including quite a few sexually transmitted ones, aren’t even impacting fitness to any significant degree despite the fact that they’re deadly (which is part of why there are so many of them still around) – if you die at the age of 35, after having had 10 kids, for all practical purposes the disease doesn’t really matter all that much in the big picture. To me, the interesting question is not how a cultural adaption like circumcision might have provided the group with an evolutionary advantage, but rather why it was not so disadvantageous to the group as to go out of style completely over time). In her book she’s finding ‘evolutionary explanations’ all over the place also in places where it seems rather obvious to me that really none need even exist – these are not the only examples.

Aside from this, it’s really quite good, interesting and fun – there’s lots of good stuff as well. I’ll post more on the book later on.

Fundamentals of Genetics

…by Peter Russell. Started it today, have read most of the first chapter on Cell Structure and Cellular Reproduction. There are two big reasons why this book is a good buy for a guy like me: a) “Fundamentals of Genetics is a text ideally suited for courses whose students have a limited background in biology and chemistry, or for those in which time constraints prohibit the use of a more comprehensive text. The new text is approximately 25 percent shorter than Genetics, making it ideal not only for one-semester courses in genetics, but for one-quarter and summer courses as well.” b) “each chapter of Fundamentals of Genetics is self-contained so that you can use the chapters in a sequence that best accomodates your own teaching [learning...] strategies.”

It’s relatively accessible and you can take it one chapter at the time. That’s how I’ll proceed. I know it’ll require some heavy lifting along the way, so I don’t expect to finish it anytime soon. Remember that if this book constitutes the curriculum of a 10 ECTS course, it corresponds to something like 250-300 hours of work (if -ll- a five point course, it’s still 125-150 hours). I don’t have an exam to look forward to, but I’d like to learn some of this stuff and that’ll take time. Maybe I’ll quote from it here, maybe I won’t, haven’t really decided yet.