Human OCA2 Gene Is Responsible for Eye Color and Skin Color

 
Oculocutaneous albinism Type II [OMIN 203200] is a common type of albinism (especially in Africans). It characterized by loss of pigment-containing melanocytes in the skin. The genetic locus of this phenotype was localized to a single region on chromosome 15 and the gene was named OCA2 (oculocutaneous albinism Type II). See Beull's Blog; a blog written by a young man suffering from oculocutaneous albinism Type II.

The gene maps to 15q11-2-q12 and it has 24 small exons spread out over more than 350 kb (350,000 base pairs) [EntrezGene 4948]. The 836 aa coding region produces a protein called P protein, which has been localized to the membranes surrounding melanocytes.

The function of P protein is not well understood. It seems to play a role in the processing and trafficking of proteins that are localized to melanocytes. There is data to suggest an interaction with the melanocortin-1 receptor (MC1R OMIN 155555), a gene involved in the tanning response in fair skinned individuals. Whatever the exact role of P protein, it is clear that severe disruptions of OCA2 result in reduced numbers of melanocytes and low levels of melanin pigment in the skin.

The association between mutations in OCA2 and eye color has been known for some time. The human gene is the ortholog of the mouse pink-eyed (p) dilute gene. A gene scan for eye color variants in a Caucasian population from Brisbane, Australia revealed that 74% of eye color variablity localized to OCA2 (Zhu et al. 2004).

Duffy et al. (2007) examined the known variants of this gene. There are three dozen different alleles segregating in humans. Most of these have no effect on the amino acid sequence of the protein. Substitutions at amino acid 419 effect eye color: the present of glutamine 419Gln is strongly associated with green or hazel eyes. All other variants this position product brown eyes [OMIN 227220].

Blue eye color is associated with neutral mutations that map to the 5ʹ end of the gene suggesting that the actual change that gives rise to blue eyes is in the regulatory sequences that control expression of OCA2. The idea is that down regulation of P protein leads to reduced levels of melanin and this is what gives eyes a blue appearance (Strum and Frudakis, 2004).

The standard explanation for human eye color is based on a two-factor model (see The Genetics of Eye Color). We now know that this model is too simple. The main eye color gene (OCA2) has blue, green, and brown alleles but the expression of the corresponding phenotype is modified by a number of other genes.

Zhu, G., Evans, D.M., Duffy, D.L., Montgomery, G.W., Medland, S.E., Gillespie, N.A., Ewen, K.R., Jewell, M., Liew, Y.W., Hayward, N.K., Sturm, R.A., Trent, J.M., and Martin, N.G. (2004) A genome scan for eye color in 502 twin families: most variation is due to a QTL on chromosome 15q. Twin Res. 7:197-210. [free reprint]

Sturm, R.A. and Frudakis, T.N. (2004) Eye colour: portals into pigmentation genes and ancestry. Trends in Genetics 20: 327-332. [free reprint]

Duffy, D.L., Montgomery, G.W., Chen, W., Zhao, Z,Z,, Le, L., James, M.R., Hayward, N.K., Martin, N.G. and Sturm, R.A. (2007) A Three-Single-Nucleotide Polymorphism Haplotype in Intron 1 of OCA2 Explains Most Human Eye-Color Variation. The American Journal of Human Genetics 80: 241-252. [PubMed]

Cell Phones Can Cause Death in Hospitals

 
Friday's Urban Legend: FALSE

Hospital equipment unaffected by cell phone use, study finds

ROCHESTER, Minn. -- Calls made on cellular phones have no negative impact on hospital medical devices, dispelling the long-held notion that they are unsafe to use in health care facilities, according to Mayo Clinic researchers.

In a study published in the March issue of Mayo Clinic Proceedings, researchers say normal use of cell phones results in no noticeable interference with patient care equipment. Three hundred tests were performed over a five-month period in 2006, without a single problem incurred.

Involved in the study were two cellular phones which used different technologies from different carriers and 192 medical devices. Tests were performed at Mayo Clinic campus in Rochester.

The study’s authors say the findings should prompt hospitals to alter or abandon their bans on cell phone use. Mayo Clinic leaders are reviewing the facility’s cell phone ban because of the study’s findings, says David Hayes, M.D., of the Division of Cardiovascular Diseases and a study author.

Cell phone bans inconvenience patients and their families who must exit hospitals to place calls, the study’s authors say.

The latest study revisits two earlier studies that were done ‘in vitro’ (i.e., the equipment wasn’t connected to the patients), which also found minimal interaction from cell phones used in health care facilities. Dr. Hayes says the latest study bolsters the notion that cells phones are safe to use in hospitals.

PZ's Birthday Blogfest

 

Read all the birthday messages at A Blog Around the Clock, archy, and Living the Scientific Life (grrlscientist).

See PZ's response at Really, it's just the blink of an eye on a geological scale. Leave a message for him on that thread.

Have You Heard of Australia?

 
John Wilkins posted a comment on the thread about favorite countries. He said,

Nobody likes Australia, because nobody has ever heard of it. And that's just the way we like it. So don't spoil it, hey?

I take that as a challenge. I think there are lots of reasons for not liking Australia so I'm going to put it to the test. Anyone reading this post will have heard of Australia and I'm even showing you where it is on a world map (see below). Now let's see if people start liking Australia.

Why Children Love Their Security Blankets

 
A recent study examined Why Children Love Their Security Blankets. This is a subject most parents are familiar with and not just because of Linus. The photo on the left shows my daughter when she was much younger. She was trying to retrieve her pink blanket ("Cubby") after it had been washed and hung out to dry. The photo below is of my son showing off "Baba" after five years of continuous use—I think he still misses Baba. (There're probably going to kill me for posting these photos.)

The study asked whether children felt a special attachment to their favorite things ...

New research, published today in the international journal Cognition, suggests that this might be because children think the toy or blanket has a unique property or ‘essence’.

To support this theory, Professor Bruce Hood from the University of Bristol and his colleague Dr Paul Bloom of Yale University, USA, showed that 3-6 year-old children have a preference for their cherished items over apparently identical duplicates.

Children were introduced to a scientific looking machine that could copy any object but was in fact a conjurer’s cabinet where an accomplice inserted replica items from behind a screen.

Professor Hood said: “When offered the choice of originals and copies, children showed no preference for duplicates of their toys unless the object to be copied was the special one that they took to bed every night. A quarter of children refused to have their favourite object copied at all, and most of those who were persuaded to put their toy in the copying machine wanted the original back.”

Duh!

I have a favorite coffee mug, a favorite chair, a favorite shirt, a favorite pair of sunglasses, and a favorite blogger. I don't want no friggin' copies either and I wouldn't put any of those things in the copy machine. (Well, ... maybe I'd try putting PZ Myers in the copier, just to see what happens .... )

Security blankets and other things don't have any special "essence" that needs to be explained. Their unique property is their history. There's only one thing that was given to you by some special person and uniquely belongs to you. You can't copy that. Children aren't stupid. They know the difference between the original and some cheap copy.

This looks like the kind of study that discovered exactly what everyone expects but they have to hype the results in order to make it look exciting. Did anyone really think that my daughter or my son would have traded their very special blankets for a mere copy? How many of you have tried to con your kids when the security blanket got lost, as they invariably do? Didn't work, did it?

Don't anyone try and swap my coffee mug. If you break it, you die.

Happy Birthday PZ Myers

 
I don't remember exactly when I first encountered Paul Z. Myers, as he was known in those days. (Yes, I do know what the "Zed" stands for but I'm not telling.) I think it was in 1994, or possibly 1993. PZ was a brash youngster jumping into the maelstrom of talk.origins with both feet. It wasn't long before he established himself as one of the regular Howlers. I remember that he had a special fondness for Ed Conrad back in those days. Ed had just made an Earth shattering discovery—man was as old as coal—but Prof. Myers wasn't buying it.

I remember getting into a rather heated discussion about something or other in order to set PZ straight. That happened a lot back then. I suspect it was an attempt by me to correct his adaptationist tendencies. You wouldn't know it now but he was actually a fan of the Richard Dawkins version of evolution in the olden days.

Times have changed. And today he's 50 years young! Happy birthday PZ. (The photo was taken on the Sandwalk. That's not an outhouse we're sitting in. It's a small shelter at the end of the path leading directly from the base of the garden to just before it turns left into the woods.)

I looked for his earliest posting to talk.origins in order to present it to him and the blogger world, but I couldn't find it. The best I could do is this one from Oct. 1, 1997. You'll see that even though he was much younger then, he still had what it takes to explain complex ideas to the average reader—although he does seem to go on and on about this "pharyngula" thingy. It's a harbinger of what's coming when he sets up his blog.

... Raff is contradicting Richardson in a way. Raff says "all chordates ...pass through a pharyngula" while Richardson argues that "there is no highly conserved embryonic stage". My main beef with the Richardson article is not the bashing of Haeckel (he is actually quite reasonable in his comments on that matter), but that he is addressing a straw man. He disproves the *Haeckelian* version of a phylotypic stage, that is a stage when all vertebrates are virtually identical, but I don't consider that a viable possibility to begin with. In the quote above, Raff basically outlines the components of the phylotypic vertebrate: somites, pharyngeal arches, notochord, etc. It does not include specialized trophic structures, precise numbers of somites, or a specific size (when Collins published that nonsense claiming all vertebrates passed through a phylotypic stage when they reached the size of 7-8mm, I know of a few jaws that dropped...especially in the zebrafish community, where we work with an animal that doesn't exceed 3mm until it is well into post-hatching larval stages).

For a good example of the difference, look at Fig. 10 (the last one)in Richardson's paper. This is a set of drawings of the heads of various vertebrate embryos, drawn from photographs and far more accurate than Haeckel's stuff. Richardson's point with the figure is to say, "See how different all these animals are!", and yes, there are lots of superficial differences between the embryos.

When I saw that figure, though, my first thought was how much *ALIKE* they all were. All of them were unmistakeable chordates. All had pharyngeal arches, all had somites, all had that same general shape.

I've never seen Dr. Moran use subtlety in any way -- unless, perhaps, you consider public disembowelment a form of understatement?
Paul Z. Myers
July 10, 1997Richardson was also blurring the boundaries a bit himself. I found the comments about my favorite animal, the zebrafish, a bit troubling. He arbitrarily decided that the criterion for the phylotypic stage in fish was the tailbud stage, the time when the tail first extends off the yolk. This is a criterion that excludes comparison with the chick, for instance, and also causes serious problems for comparisons with teleosts. Zebrafish develop remarkably rapidly, and have a relatively small yolk. The tail buds early, well before the pharyngula stage. That means he looked at zebrafish at this stage and claimed they lacked branchial arches altogether! Just six hours later, though, this animal would have a very nice collection of pharyngeal structures. He has done this for all of these animals: defined some specific criterion for the phylotypic stage, looked at the animals at this one time point, and found variation in certain features. This is fine for demolishing the accuracy of Haeckel's figures. It is *not* good for revealing fundamental homologies between these animals. Chicks do not have just two pharyngeal arches, except at the particular stage Richardson restricted himself to. Zebrafish do not lack arches: they have a very lovely set of six pairs...just not at that one particular time.

He is perfectly correct in showing that the explicit similarities implied in Haeckel's drawings are false. However, note that he does not call Haeckel a fraud in that paper -- what he suggests is that Haeckel was drawing a *stylized* (his word) rendering of the animals. Haeckel was blurring together stages and features to try and put together a stylized composite...admittedly exaggerating and deleting features to fit his thesis. That was wrong. He was caught in it, too, over a hundred years ago.

I think, though, that Richardson has gone too far the other way. He seems to be demanding near-photographic resemblance at a single narrowly defined point in development. That is just too restrictive a demand, and conceals the underlying similarity. I can't think of a single vertebrate embryo that lacks pharyngeal arches; that's too important and universal a feature to deny its significance by saying they don't all have precisely five arches at the same time that they have a tailbud.

There is one final irritation in that paper. Richardson claims that the persistence of the 'myth' of the phylotypic stage is in part due to the fact that so few people actually look at comparative embryology. I would turn that around and accuse him of a rather narrow-minded perspective on comparative embryology. I've done a fair amount of vertebrate embryology, but I've also got several years of work in arthropod development, and have spent a fair amount of time studying marine biology. One reason I can look at Figure 10 and see the huge similarities is that I've also looked at insect and crustacean and annelid and mollusc and echinoderm embryos -- and boy, they don't look nothin' like those chordates at *any* time.

They Like Us, They Really Like Us!

 
BBC News has just published their World Service Poll.

The poll asked 28,000 people in 27 countries to rate a dozen countries plus the EU in terms of whether they have a positive or negative influence.

Canada, Japan and the EU are viewed most positively in the survey.

The competition wasn't too tough 'cause Australia wasn't even in the running. The battle between Canada and Japan was neck and neck until the last round when they counted the absentee ballots from Florida. There are a lot of Canadians in Florida at this time of year.

Canada and Japan had identical "mainly positive" votes but Canada wins first place because it had fewer "mainly negative votes." Tough luck, Japan, maybe next year.

The USA beat out North Korea, Iran, Venezuela, and Russia. Way to go USA! You're number 8! You're number 8!

Jennifer Smith Is Going to Meet Stéphane Dion

 
You remember Jennifer Smith, don't you? She lives in Milton, Ontario. That's the place made famous by PZ Myers 'cause he stopped for a few days to get his car fixed.

Well, it turns out that Jennifer went to a town hall meeting with her MP, the newly Liberalized Garth Turner. During the meeting she so impressed her MP that he invited her to meet with our future Prime Minister next week [All Politics Are Local]. (That's Dion in the picture, with his dog Kyoto.)

Hey, Jennifer, ask him if he'll increase reseach funding when we elect him next Fall.

The Low-Fat Diet Flunks Another Test

 
The title comes from an article by John Tierney on his blog [Tierney Lab: Putting Ideas in Science to the Test].

It's not really news. Low-fat diets have been challenged for years. There is good evidence that the Atkins diet really works for some people and it's healthy. Tierny gives us a quotation from a recent New York Times article that reported on a massive study recently completed.

The largest study ever to ask whether a low-fat diet reduces the risk of getting cancer or heart disease has found that the diet has no effect.

The $415 million federal study involved nearly 49,000 women ages 50 to 79 who were followed for eight years. In the end, those assigned to a low-fat diet had the same rates of breast cancer, colon cancer, heart attacks and strokes as those who ate whatever they pleased, researchers are reporting today.

‘’These studies are revolutionary,'’ said Dr. Jules Hirsch, physician in chief emeritus at Rockefeller University in New York City, who has spent a lifetime studying the effects of diets on weight and health. ‘’They should put a stop to this era of thinking that we have all the information we need to change the whole national diet and make everybody healthy.'’

All studies on human diets and nutrition are suspect, in my opinion. It's just the nature of the game. There are always contradictory results.

I'm not going to say that fat is never bad for you. What I say is that you should be skeptical about all claims concerning diet and health. They all need to be taken with a grain of salt (and a pound of steak ). Whenever you hear someone claiming to have all the answers you can dismiss them without a second thought. Nobody has the answers in this field, and that includes Professors, scientists, and physicians.

Intelligent Design Creationism and the History of Life

 
Denyse O'Leary repeats a common criticism of evolution over on Post-Darwinist [Response to student: Darwinian evolution not random?/ ID is God of the Gaps?].

On the face of it, Darwinian evolution is highly improbable or impossible on mathematical grounds. I mean that the history of complex life on earth (600 mya?) does not likely give us the resources we need for the random mutations. Once the Big Bang theory made it possible to establish an age for the universe (approx 13 bya) and the Earth (approx 4 bya), Darwinism was certain to come under attack.

600 million years is more than enough time for complex single-celled organisms to evolve mechanisms of associating to form complex multicellular organisms. This probability argument is just fancy hand-waving designed to impress the uninformed. (The fact that it's also made by the uninformed is ironic, but not surprising.)

But the real hypocrisy of the intelligent design creationist (IDC) community is in not coming up with a better explanation. Here's your big chance, Denyse. Why not give us a thumbnail sketch of how intelligent design creationism explains the fossil record of animals over the past 600 million years? While you're at it, you might throw in a brief description of how IDC accounts for the genetic data. You know, the genetic data that shows a perfectly reasonable rate of random mutations?

None of the IDiots have ever done this. They rant and rave about how improbable evolution is but they never give us an alternative that explains the facts. Why is that?

I'll make it real easy for you, Denyse. You don't have to explain everything. I'll be quite satisfied if the intelligent design creationists can give me their version of shark evolution. You can start with the separation of bony fish from cartilagenous fish about 450 million years ago. How did God do this? Why did He do it?

You can explain the appearance of Orthacanthus about 250 million years ago and why they look so similar to the species that lived a few million years earlier. Then you can tell us why God waited until 155 million years ago before creating the lamnoids that gave rise to modern looking sharks like the big white shark. Along the way, we eagerly await your explanation for why so many of those species are no longer with us. Did God get angry with them or does he just discard them as useless junk whenever He gets around to updating the latest model?

Here's a cladogram to help you out. When can we expect a response?

Science Blogging and Podcasts

 
Hsien Hsien Lei at Genetics & Health is experimenting with podcasts. She's figured out how to put a podcast on her blog. This is impressive. I haven't been able to do it ... yet.

See the result at Genetics and Health Podcast - Reflecting On My Role. I'm looking forward to more podcasts and to seeing how the experiment plays out.

UPDATE: I'm going to try and embed a podcast. Here's the Nature podcast from March 1, 2007 (I hope).


powered by ODEO

CBC

Canada .... hmmmm

 
You have to watch it right to the end ..... I don't know whether to laugh or cry (it's pretty funny).



[Hat Tip: Canadian Cynic]

Fairy Rings

 
I look at the botany photo of the day every day. This is a service provided by the Botanical Gardens at the University of British Columbia and I really appreciate their attempt to wean us away from animals.

Usually the photographs are spectacular closeup images taken with cameras that are much more expensive than mine. But yesteday's picture was from Google Earth! It shows 100 year old fairy rings near Kensington Palace in central London. The rings are probably caused by Marasmius oreades. Find out how a little fungus can make rings visible from so high.

Innocent Man Released from Jail

 
Mahmoud Jaballah is called a "terrorism suspect." He has been in jail for five years but he's never been found guilty of anything. That means he's an innocent man according to my sense of justice and he'll remain innocent until proven guilty.

Yesterday he learned that he will soon be released. Today's Toronto Star has the story [Terror suspect ordered freed].

Toronto terrorism suspect Mahmoud Jaballah will be released on strict bail conditions after more than five years in jail without charges, despite government protests he remains a danger to Canada.

His release comes on the heels of last month's Supreme Court ruling that struck down an immigration law as unconstitutional and deals another blow to the government's handling of security cases involving non-citizens.

Yeast Mitochondria

 
There's a paper in this month's issue of Developmental Cell that uses the technique of electron tomography to examine the fine structure of a yeast cell. This technique involves slicing the cell into many thin sections then taking electron micrographs of each section and reconstructing a three-dimensional model of the cell.

The species is the fission yeast Schizosaccharomyces pombe and the results are spectacular. The image on the left was part of the Bio News Net press release.

The emphasis in the paper is on the organization of microtubules. Those are the thin green lines runing down the length of the cell. It turns out that many of the vesicles and mitochondria are associated with these microtubules. Here's the abstract of the paper ..

Polarized cells, such as neuronal, epithelial, and fungal cells, all display a specialized organization of their microtubules (MTs). The interphase MT cytoskeleton of the rod-shaped fission yeast, Schizosaccharomyces pombe, has been extensively described by fluorescence microscopy. Here, we describe a large-scale, electron tomography investigation of S. pombe, including a 3D reconstruction of a complete eukaryotic cell volume at sufficient resolution to show both how many MTs there are in a bundle and their detailed architecture. Most cytoplasmic MTs are open at one end and capped at the other, providing evidence about their polarity. Electron-dense bridges between the MTs themselves and between MTs and the nuclear envelope were frequently observed. Finally, we have investigated structure/function relationships between MTs and both mitochondria and vesicles. Our analysis shows that electron tomography of well-preserved cells is ideally suited for describing fine ultrastructural details that were not visible with previous techniques.

One of the most interesting things about this paper is that it illustrates the structure of mitochondria. Look at the picture on the right from their paper. The gold things are mitochondria and they appear to be stuck to microtubules. Individual mitochondria are shown in the inserts in order to illustrate the convoluted and branching structures of those that are associated with microtubules. (The one labelled "G" is not stuck to microtubules.)

Most people don't realize that mitochondria are so complicated. Furthermore, the structures are dynamic—they can change significantly in the space of minutes.

Höög, J.L., Schwartz, C., Noon, A.T., O'Toole, E.T., Mastronarde, D.N., McIntosh, J.R., and Antony, C. (2007) Organization of Interphase Microtubules in Fission Yeast Analyzed by Electron Tomography. Developmental Cell 12: 349-361.