an easy guide to remember what a SNP is

We read about SNPs (pronounced snips) in the papers and online, we hear about them on TV, on the radio and in people's conversations. But what are they?

A SNP is used to understand someone's Story - which population they belong to and who were his/her ancestors - and what makes them the Person they are - what do they carry in their DNA.

Thus, SNPs are used to find someone's S and P i.e. SNP.

----

A SNP stands for Single Nucleotide Polymorphism.

Consider our DNA as a very very very long road, with millions of houses - which we call nucleotides - each of which has an address - we call this its "position" or "co-ordinate". Thus when we talk about a single nucleotide, we talk about 1 of the, 6 billion in the case of humans, houses that make up our road.

There are 4 types of nucleotides/houses (we call these alleles): blue (Cytosine or C), green (Adenine or A), yellow (Guanine or G), red (Thymine or T). If the houses in the photo above were a nucleotide sequence, this would have been GCTATG.

But a SNP is not just a single nucleotide, it is a single nucleotide polymorphism. What is meant by polymorphism is that the house in the middle of the photo above, say the house with address 17854853, in my road is of a different colour than the house of the same address in your road. In this case, mine is green whereas yours could be blue. In biology talk, this is equivalent to "there is a SNP at position 17854853, where I have allele A and you have allele C".

In order for a house to be called a SNP, it is required for at least 1% of the human population to have a different type of house (allele) at that address than the rest. As a result SNPs are not very common: on average only 1 in 1000 houses is different between two individuals.

"So far so good" you could say, "but why is your house green and mine blue?".

The answer is mutation. When DNA gets copied (mitosis) or when it is split in two sets of chromosomes to produce the cells that can give rise to a new organism (the gametes, i.e. the sperm and the egg), mistakes happen. What I mean by mistake is that sometimes the house changes colour, but it can also mean that a house is destroyed (i.e. deleted) or a new house can be inserted.

But this does not exactly explain your question: it only tells you why our houses in this specific address are different, but not why my house in this particular address is green and not red, and yours is blue and not yellow.

This is where the S and P come in. My house is green and yours is blue either because our ancestors were different (the S part) or because a mistake was made when either one of us got created (the P part).

----

We' ll consider at the S part first. Lets say that the tree below is a tiny part of the "tree of life". I am the green dot and you are the blue dot. You will be happy to know that we closely related since we had a common ancestor just near the green line.

(image modified from http://dragonartz.files.wordpress.com/2008/12/_vector-tree-preview2-by-dragonart.png?w=495&h=495)

Our common ancestor had a green house at address 17854853 of his/her road. This ancestor had two kids, one of which is my ancestor and the other is your ancestor. A mistake was made when your ancestor was created and his house turned from green to blue. And just so that you do not get offended, mistakes are not necessarily bad. They can be good (advantageous mutation), bad (disadvantageous mutations) or they can make no difference whatsoever (neutral mutations). We now know that most often mistakes make no difference.

So the reason why my house is green and yours is blue is explained by who were our ancestors! Differences are explained by our history but this also means that looking at these differences we can understand our history. Find out what is our story. And this is one of the two reasons why SNPs are important: they allow us to understand where we come from and why we are the way we are!!!

Let me give you an example. I choose lactase persistence since it is a very clear and very famous example and because one of the people I worked with during my PhD worked on this.

Lactase is the enzyme that digests the lactose in milk. In some humans lactase activity decreases after weaning (we call these lactose intolerant). In others, lactase activity persists at a high level throughout adult life (we call these lactorse tolerant). Biologists wanted to find out how did this difference arise, what makes these individuals different. For this reason they had to find the SNPs associated with lactase persistence.

Two SNPs have been identified as the best able to explain why one individual is able to digest lactose and another one isn't. The first is "rs4988235 (−13910C→T)".

Don't be scared! All this means is that:

1. the name of the SNP/house is rs4988235,
2. the SNP/house is found 13910 houses before the start of the LCT gene, the gene makes the lactase enzyme (for the record the house's actual address is 136325115),
3. the house can be either of type blue (C) or red (T), and
4. the ancestral house was of type blue (C) so when one has that type of house is lactose intolerant, whereas if their house is red (T) they are lactose tolerant.

The other SNP is "rs182549 (−22018G→A)". You can now guess what this SNP is from my explanation above.

What Bersaglieri et al (2004) did was to look at those two SNP addresses in a number of individuals and count how many of them had one type of house or the other. In other words they wanted to determine the frequencies of the persistence-associated alleles (T in SNP rs4988235 and A in SNP rs182549). The individuals they used came from three populations (European Americans, African Americans, and East Asians) and for each of these individuals they knew if they were lactose tolerant or intolerant. What they found was a correlation between how common were the persistence-associated alleles and the level of lactose persistence in a population. European Americans, the population with the most lactose tolerant individuals, had the greatest percentage of persistence-associated alleles in these SNPs(77%). In contrast, the other two populations show low lactose tolerance and they have the lowest frequencies of persistence-associated alleles in these SNPs (13-14% in African Americans and 0% in East Asians).

So what did we understand about human history from looking at these SNPs? Based on this data, Bersaglieri et al (2004) estimated that these mistakes (C to T in SNP rs4988235 and G to A for SNP rs182549) rapidly became more common at a time near the estimated origin of dairy farming in northern Europe i.e. ∼9,000 years ago. They thus concluded that added nutrition from dairy appears to have provided an advantage in northern Europe. When dairy farming appeared, humans could not drink the milk. Mistakes happened in the DNA of some of these people and since being able to digest lactose gave an advantage, these mistakes spread through the population (i.e. the frequency of the persistence-associated alleles increased). In fact, these mistakes are in the top 3 of the most advantageous mistakes estimated to date.

------

Now lets talk about the P.

Our DNA does not only tell us about our past, but also about our present and our future. In other words, it tells us what we are and what does this mean in terms of our future. We get this information, in other words we understand what makes us the Person we are, when we compare our DNA to that of others. And one of the main reasons we want to do these comparisons is for our health. To predict what will happen to out state of health in the future. I will use cancer as an example.

Almost a decade after the sequencing of the human genome, new technologies have been developed that - given this sequence - make the creation of individual "SNP maps" or "SNP profiles" easier and easier. They also - and maybe more important - make it a lot cheaper.

But what are SNP maps? (I will use SNP maps from now on but SNP maps and SNP profiles are the same thing).

As I mentioned before, most of our DNA does not differ from person to person. Thus, in order to understand what causes our phenotypic differences - e.g. why do I get breast cancer and you are not - we do not need to compare the whole of our genomes. We only need to look at those addresses where there are known differences in the types of house found there. In other words we just need to look at the parts of our DNA which are polymorphic. Our SNPs that is.

A SNP map is like a registry that says what type of house (allele) we have in those addresses (houses) which are known to differ between individuals. It looks a bit like this: individual X at SNP rs4278313 (whose address is 105123) has allele C, at SNP rs9708285 (whose address is 105195) has allele T, at SNP rs9751025 (whose address is 105213) has allele A, etc etc.

But this is not the only source of information that doctors have for each cancer patient: they also know about their phenotype i.e. what cancer they have, for how long, what treatment worked for them and what did not, their sex, their age, their lifestyle choices, etc. etc.

You may now ask me "since doctors have all this other information, why are SNP maps helpful?".

The reason why SNP maps are important is that they can lead to faster and personalised medicine since they can be used

(a) for the better understanding of the cancer (red part of the following figure) but also

(b) for diagnosis and personalised treatment (blue part of the following figure) .

I would say that currently we are mainly using them for the former, but i will explain both of these below.

(taken from http://nci.nih.gov/images/Documents/f6e06278-e717-4465-b5b4-fda72f95584b/cancer41.jpg)

(a) understanding the biology of cancer: when scientists compare SNP maps of individuals with the same cancer, they can find in which SNPs these patients have the same allele and therefore which are the candidates for the cancer-causing mistakes (mutations). In other words, if individual A and individual B both have prostate cancer and they also have allele T at SNP rs4430796, allele G at SNP rs7501939 and allele C rs3760511 C, when men without prostate cancer have C, A and A respectively, then scientists assume that these SNPs are likely to be associated with this cancer. Of course these comparisons happen with a large number of individuals from many populations.

Similarly, SNP profiles can be compared to better understand the response to cancer treatments. If individual A and individual B both have prostate cancer, both got a lot better when prescribed a specific drug and both have the same alleles at a number of their SNPs, then scientists assume that these SNPs a likely to be associated not only with this cancer but also with this treatment.

(b) diagnosis and treatment planning: the stage above is aiming at personalised medicine. In the previous scenario it means that once the SNPs most associated with this cancer have been identified, a test is created to test each man for this set of SNPs. If they are found to have the cancer-causing alleles in these addresses then they have to check their prostate a lot more often than others who do not. In this way the cancer can be diagnosed in the earliest stage, increasing the chances of those people of living a long life. By the way, the first such test exists. A company called Proactive Genomics created two years ago the

Focus5™ Prostate Cancer Risk Test.

What stage (a) is aiming at is the following scenario: patient enters the room, doctor compares the patient's SNP map to the SNP maps of cancer patients. From this comparison the doctor is able to identify immediately, not only the specific nature of the cancer of the patient but also the best treatment for this particular patient. Cancer is diagnosed and treated at a very early stage and patient has less chances of dying because of the cancer.

However, we should not forget the ethics of this "mapping" and also to take into account the patient's psychology. Patients react differently to news about their health. They make a number of decisions some of which could prolong their lives, but others may have the opposite effect. The question you need to ask yourself is: Would you like to know that there is a probability that you will get cancer? Would you have liked to know this at the age of 18? Or 15? or 5? Would you like other people to know about this? Will it be possible for you to restrict who knows and who doesn't? How is this knowledge going to affect your life?

-----

So from now on, when you see or hear something about SNPs remember your S and your P: remember that the importance of SNPs is that they can tell us things about our hiStory and they can lead to Personalised medicine.

THE SCIENCE VOTE (#SCIVOTE) MOVEMENT: ORIGINS

Over the last 3 weeks I have been following very closely what was happening before, during and after the recent UK elections but from a scientist's point of view. I copy-pasted every article I could find into Word documents. In the end, these Word documents were more than 300 pages long. I also read all of them and I have been following the twitter discussions as well.

Finally, I wrote the following article for a major Greek newspaper (for those of you who understand Greek and this will not all "sound Greek to you" the weblink for the Το κίνημα "Ψήφος στην επιστήμη" paper is http://www.vimaideon.gr). This is my attempt to translate it. I am saying attempt because the language centre of my brain does not understand anymore which are Greek expressions and which English.

I would really appreciate it if any of the people that were actually part of this movement could tell me which points I've understood wrongly: a third-party always sees things differently and a lot of times not correctly. I can think of many points that might be wrong or annoy people.

THE SCIENCE VOTE MOVEMENT: ORIGINS

The Lisbon Treaty and then European Strategy for 2020 stressed, ambitiously perhaps, the importance of long term investment in knowledge - produced through science and technology - as the only way of exiting from the financial crisis. Politicians in every corner of Europe (and beyond) indicate that the goal of modern society should be a knowledge-based economy.

Nevertheless - whereas the U.S.A., China and India increased their funding for science - Great Britain and other European countries in their general panic to reduce public deficit and debt, announced cuts in public investment in science and technology. In other words, although governments recognize the importance of these investments, they do not apply them. In this way they are risking the future of their country, since a reduction in funding today will lead to future lack of scientific expertise needed to boost economic growth. [businesses seem to agree already on this]

Many British people noticed this paradox during the recent election campaign and their disagreement resulted in the "Science Vote" movement or «#scivote» if one is to use twitter terminology. But what is this movement? What were its aims? Did it succeed in British elections? What is its significance for Greece?

WHEN VOTES MET SCIENCE

Two months before the British elections of May 6th, most people would have bet on a victory of the Conservatives, a party that had made it clear in their manifesto and before the elections that they would promote the greatest and more immediate reductions in the budget for Science and Technology. Faced with this frightening scenario, natural and social scientists, science journalists, skeptics and bloggers united to bring for the first time in the center of discussions fundamental issues concerning science, such as funding, free speech, the importance of evidence-based policy, etc. This had never happened in any country.

The first members of the «#scivote» movement, also could be called "science activists", decided to turn any votes to "science votes" i.e. to inform the British public on the scientific policies of each party, in order to enable them to judge and vote for the party with the best science policy.

The first to react was the non-profit organization "Campaign for Science and Technology" (CaSE), who on the 8th of March 2010, with the support of many major British scientists sent a letter in the Times to the political parties asking them to submit a detailed "scientific" manifesto.

One day later, on March the 9th, the Royal Society of Chemistry organized the first "scientific debate" and first public debate in the House of Commons streamed live over the Internet. In this debate took part representatives from the three major parties. The Liberal Democratic Party was represented by Dr Evan Harris, a leading supporter of and perhaps on the most active politicians in science and technology issues for over a decade. For example, he was a supporter of the reform of libel law in the UK, which made a lot of scientists afraid of speaking in public about their research and their views, in case they were sued by large organisations whose interests were affected [as it happened with Simon Singh]. Of course, not everyone reacted positively to Dr. Evan Harris's actions: extremists named him "Dr. Death", because of his views on abortion, euthanasia, stem cells and animal experiments.

These two events provided an initial impetus to the «#scivote» movement and, thanks to Twitter among other reasons, the movement quickly grew larger. Of particular help was that the Minister for Science, Lord Drayson, like many members of the House of Commons Select Committee on Science and Technology, had a strong and constant presence on twitter. Therefore, through the use of new web tools, there has been over the past few months continuous and direct dialogue on issues of science policy because the views of the movement reached directly the ears of politicians.

The voice of science activists was so strong that it even reached the media. Despite the heat of the election season, there was an increased focus on science in the press: in the last weeks before the election, Mark Henderson in the Times Eureka blog and Martin Robbins in the Guardian, wrote almost daily on scientific policy. The latter - together with five of the most famous British scientists - asked all political parties the same ten questions, so that British people are able to easily compare the science policies of the parties.

After an election season with so many "firsts", those who had bet on a clear victory of the conservatives were regretting it. Nick Clegg, the LibDem leader, had unexpected success in the television debates and in the polls the percentage of his party was increasing. This positive atmosphere gave hope to many members of the «#scivote» movement, since the LibDems were the party that understood the contribution of science and technology in the recovery from the crisis the best. Hence, the slogan «geek the vote, vote LibDems» was created.

THE DAY OF CRISIS

May 6th, 2010. Conservatives get 36.1% of the vote, Labour 29% and the LibDems 23%. As many feared there was a hung parliament, a result of "European style" as some people put it, which shocked Britain. Shocked was the «#scivote» movement as well. "Did we lose?" they whispered. "Were the polls so wrong? Did nobody read the articles we wrote in the press and online?". Anyone would be thinking the same since at first glance the results actually looked like a "disaster":

1. The number of MPs who were in some way related to science and technology declined from 86 to 71 and only one of the old "science activists" would be present in the parliament. Of the remaining, some retired and others did not get elected. In the second category is Dr Evan Harris, one of the "leaders" of the movement, who lost for 176 votes.
2. Secondly, the Liberal Democrats, the party that expresses best the beliefs of the «#scivote» movement, not only did not win seats as was expected from the very positive election exit polls, but lost five seats (out of the 62 that they had, they got only 57 seats in the recent elections).

Looking closer however, it revealed that the results are not as disastrous as they seem. It might be true that some of the previous MPs positive towards science did not get elected, but many of the newcomers also have a background related to science. The absence of Dr Evan Harris, remains really tragic however. Nor the LibDem performance was that disappointing: the share of votes did not fall as would be expected given the decrease in the number of seats, but increased from 22.1% in 2005 to 23% in 2010. The problem was the "First-Past-The-Post" electoral system, which is considered by many (among them the LibDems) as a system that does not represent what the public wants.

THE PUBLIC SPOKE BUT WHAT DID IT SAY?

For nearly five days after the election, Nick Clegg has negotiated with the two major parties so that they can agree on a coalition. Finally, on Tuesday, May the 11th it was announced that there would be a coalition between the LibDems and the Conservatives.

The fact that the LibDems would be part of the government and therefore had some influence in the administration of the country, did not relieve science activists. Clegg would be able to negotiate only a few points in the coalition agreement between two parties. It would therefore be unlikely that one of them was science. Furthermore, the scientific policy of the Conservatives differ considerably from that of the LibDems, so it was even more unlikely to find a compromise so quickly. For example, the Conservatives support the creation of nuclear power plants, while the Liberals are completely opposed to it.

All would be judged by the agreement between two parties, announced in the afternoon of Wednesday, May 12th, followed by the first public speech of the two leaders of the coalition. This agreement did not clarify at all the situation since it did not contain even once the word science. Instead, it resulted in new questions. "Why did they not mention science? Did they not discuss the issue or did they disagree on many points?" wondered members of the "#scivote" movement.

Their hopes were not lost though. Key would be who would be chosen for the positions of Secretary of State for Enterprise, Innovation and Skills (BIS) and Science and Universities Minister.

After almost a week of suspense for the «#scivote» movement, finally came some good news. First it was announced that Secretary of State for Enterprise, Innovation and Skills would be a LibDem, Dr Vince Cable, who has a degree in Natural Sciences from Cambridge University and a Ph.D. in Economics. Shortly afterwards it was announced that the Conservative David Willetts was appointed Minister of Science and Universities, also known as "two brains" because of his residing hairline, but also because of his cleverness. Willetts studied Politics, Philosophy and Economics at Oxford University. This option was particularly welcome because Willetts had argued in 2007 that science had important role in all sectors of society and that it was essential for all members of the cabinet to appreciate the importance of science and technology in making policy decisions.

AND NOW WHAT?

The team Cable-Willetts was that best that science activists could hope given the current allocation of seats in the British Parliament. It is a great advantage that both ministers are members of the cabinet, and thus they will be able to express their views on science and other issues. An even greater advantage, however, is that the LibDem Dr Vince Cable will oversee Willetts, a smart Conservative, who is pro-science, who also had the respect of Chancellor George Osborne, the one who will approve all ministerial decisions in the new government. Therefore, the future of British science will be influenced by a team with good awareness of the state of science policy before they even begin, and who has the tools and the conditions to bring good science policy about.

Of course not everything is perfect. Many would prefer an practicing scientist in the position of Minister of Science. Also, the movement did not agree with everything Cable and Willetts have said in the past. An important role will also play who will be the members of the House of Commons Select Committee on Science and Technology. There are many battles to be fought in the parliament and outside in order to even keep the British science at its current high level.

The elections were only the beginning. The first battle in which no one can say with certainty whether the "science vote" movement lost or won. On the one hand, the elections reminded members of the movement that they remain a minority. That said, we they should be proud because, as the former Minister of Science Lord Drayson said "#scivote now has a real voice & influence in politics so keep it up! And support the next science minister whoever she/he is".

Now the "#scivote" movement should begin the important and urgent task of educating new MPs on scientific matters. Of convincing party members that science is more than one source of information and knowledge. That it is an important driver of the economy that will play a crucial attention to major issues such as energy independence, and that there should be strong support, even in times of economic cutbacks.

Also, the movement should push for a system that will not be based solely on public funding, but also a "charity-capitalist" organizations, such as The Wellcome Trust, which by their nature are long-term strategy and ambitious and risky objectives which governments by their very nature could never be set.

Furthermore, activists of science should not just preach to the believers. They should turn to those who have not had an interest so far for scientific policy, because only in this way there will changes in the way politics is practiced. Finally, they must convince the new Minister of Science and Universities to use twitter, in order to continue the constructive dialogue they had with the previous minister.

If the "science vote" movement does not act in continuity and consistency, it is certain that science will be one of the areas most affected by the crisis, and thus there will be uncertainty for the future.

But the important thing is that thanks to the science activists, for the first time in history science and technology became an election campaign issue. We must therefore ask ourselves what were the circumstances and why did this movement leave today the area of consensus and entered politics.

Could such a phenomenon have been created in other countries, such as Greece?

NOTE: some of the ideas/thoughts of this article were taken by the various articles I read. I will be linking to these articles in the next few days.

UK Election and #SciVote (1)

Just because I am a geek, I decided to do a little exercise of my own even before the we even know what the government in the UK will be.

First of all for "after-election" articles related to science vote from people that actually know about this topic please click here , here and here.

What I did is that I took the list of MPs published in the Eureka Zone Times paper by Mark Henderson last week.

Given this list, I added next to each constituency the candidate that won. For those where there was information on science background in THAT list I kept this information.
You can find both the original list and the "after election" list here.

So there are 2 massive problems with this dataset:
1) not all 650 constituents are on there and
2) when we say that an MP has a science background as Mark Henderson mentioned

1. "we don't mean to suggest that you need to have a background in science to become an effective Commons advocate for it" and
2. a background in science does not necessarily mean that an MP will be actively engaged in it, or promote it in Parliament.

So you could say "what is the point of all the graphs you made?". As a scientist I do feel very awkward about the plots that I will show you, but because I have already spent too much time on this, and because I do not really have the time to go look in detail all the backgrounds of all 650 MPs, I decided to post them anyway. In addition, I am pretty sure that the people who are dealing with these issues (like the authors of the papers I mentioned above) will be doing this work anyway, so it will be a bit redundant if I did something like this. Especially since I do not have knowledge of the "political history" of each MP (e.g. what bills s/he voted and so on.

What I am saying is, I am aware that the following plots are not very well evidence-based and that they could lead to misinterpretation. If you are ok with this please read on, otherwise please leave this post (hopefully not the whole blog :P).

OK so here we go....

Out of 155 constituancies (I found a double in the list from the Times article), 70 had a "science background" and the last one for which right now we do not have the results is likely to be the 71st that is mentioned in the new article by Mark Henderson.

Out of the 70 MPs with "science background" 36 have degrees in the "hard sciences" i.e. physics, maths, chemistry, biology etc, 19 had degrees in engineering, 9 are medical doctors or dentists and for the rest it is not specified even though they are stated as having a "science background". Most of these belong to the Science and Technology Committees or held science related roles in the past (correct me if I am wrong since once again I did not have the time to check this: Graham Stringer, Malcolm Wicks, Adam Afriyie, Roberta Blackman-Woods, Rob Flello).

So then I wanted to see what is the distribution of MPs in the different parties once they have been sorted according to background:

And then I looked at each party separately:

The results are not unexpected given all those articles I have been reading the last two weeks on which I will report soon (hopefully). LIBDEMs is the party who has more MPs with science background" than with "non-science or unknown background". Labour has more or less equal proportions whereas the Conservatives (and other parties) have a higher proportion of MPs with non-science or unknown backgrounds.

So this is my little research. Of course any comments are MORE THAN WELCOME!!!

I repeat that the information I had was only for 155 constituencies out of 650 and that having a "science background" does not make you necessarily more likely to "defend science". I am not claiming that this is a complete research.

But the results are interesting nevertheless! :)