Toy Genetic Testing
“Welcome to yourself,” “get to know your DNA,” “explore your inner universe,” such slogans make up companies that offer genetic testing. Indeed, it is an amusing thing to look at the disruptions of your own genome or find out where your lineage originated from. Now it’s quite simple to do, because IT companies were able to "wrap" the results of biological research in a form that we understand. Spit in the test tube today, and after a month you are already looking at the multicolored reports on the site.
A year ago, I used the services of 23andMe - the world's largest company that provides genetic service directly to the client (direct-to-customer). Using the example of my result, I would like to tell you what lies behind such a genetic test.
We will deal with the biological part of the issue. The human genome is a complete set of genetic information, which, for the most part, is packaged in 23 pairs of chromosomes. The human genome has an enormous volume of 3.2 billion pairs of DNA bases (A, C, G or T). It is as if all the people on the planet in pairs lined up in a strongly curved curve, and we have two such lines: from mom and dad. In addition, in each of the 3.7 trillion cells of our body, the genome is the same. That is, if in our
the genetic code has sneaked in some kind of change, it is not yet possible to "recode" it.
However, from a genetic point of view, all humans are twins, because the genomes of two people are 99.9% similar. At the same time, the differences are mainly represented by point mutations, when one nucleotide changes to another. Thus, several point mutations can distinguish a curly person from a person with straight hair, healthy from a cancer patient.
Unfortunately, we do not know as much as we would like, about the connection between the symbols of the genome and visible signs. This is due to the complexity and diversity of the mechanisms that occur in the cells. For a number of signs, this connection is well shown, for example, for such as blood type, eye color or susceptibility to breast cancer.
Mutations are bio-markers, which are targeted tests 23andMe and several other companies. Now their genetic test takes into account 1 million mutations in the genome. However, these are not all possible mutations. It is worth noting that there are tests that are aimed entirely at other markers. For example, paternity tests analyze short repeats of certain sections of DNA. These plots vary greatly between families, but are almost unchanged within the same family.
')
In order to do a genetic test, you need to send a sample of your DNA. 23andMe and many other similar companies secrete DNA from saliva. It is worth noting that saliva is not the best material for DNA analysis, since the cells that it contains, like other somatic cells, can accumulate random mutations. I will not write what material and why is more suitable for DNA analysis.
The process is highly automated. You are sent a small box with a test tube, which you need to fill with saliva to the line. The test tube has a special nozzle to make it convenient to fill. When closing, the film on the nozzle is torn, and the tube is filled with the buffer solution so that the sample does not deteriorate on delivery. Then you seal it and ship it to the USA with DHL. You also need to enter a unique tube number on the 23andMe website, which will then match your DNA sample and your account. In semi-automatic mode, the bio-laboratory detects mutations and sends data to 23andMe. That is, the laboratory itself does not draw any conclusions, but only supplies raw data on mutations. The entire analysis is carried out by bioinformatics. The laboratory does not know the names either, but sees only the unique numbers of the test tubes. The result is ready about a month after sending the tube.
Test 23andMe can be ordered in almost all countries of the world, but not in Russia. Because in our country unauthorized shipping of biomaterial is illegal. There are known attempts to find loopholes in this system, but they either failed or ate too much time and nerves. I received and sent my test from Italy.
The cost of the test 23andMe is 99 dollars plus shipping. For residents and guests of the United States, delivery costs about $ 5, for Europeans it is about $ 60.
In large cities of Russia there are similar services and even 23andMe clones, but their prices are much higher, and the quality and volume of analyzes is still lower.
Before you do genetic tests, you need to decide on ethical issues. First, genetic diseases are quite insidious, and many of them are still incurable. You can carry a mutation that can lead to phenylketonuria. You may not be sick with phenylketonuria, because a copy of the same gene from the other parent is normal, but your offspring may be susceptible to this disease. Or the test may show you that you have a very high risk of developing Alzheimer's disease. This disease is characterized by impaired mental activity and usually appears after 50 years. To live with or without such information is a purely individual question.
Secondly, genetic information is to some extent common to the whole family. That is, if you are a carrier of a mutation, then most likely it came from one of your parents and it will also be passed on to your descendants. And the test result will affect not only you, but the whole family.
Thirdly, individual genetic information is a new phenomenon, and so far it is not clear how to treat its confidentiality. 23andMe protects your data fairly well, but you can open it yourself. Undoubtedly, the more data we have in the public domain, the more power our statistical conclusions have. But who knows how it will be used in the future. For example, in America, even now genetic data may affect customer insurance rates.
23andMe site gives you a clear report on test results. Everything is convenient, systematic and simple.
I have identified 4 main categories of information received. The list is arranged in descending order of importance for me:
Genealogical tests are based on large-scale studies of complete or partial genomes taken from different populations. Scientists were able to identify sets of mutations that are characteristic only for a given population (North Americans, Chinese, Australians, etc.). Having a set of mutations, you can determine which groups and in what percentage the person belongs to. Such tests have fairly good accuracy.
The graph shows my membership in the East European population. Since 23andMe does not work with Russia, the population closest to it is displayed. In principle, the result is true, because my parents are from Russia. It was interesting to find a small percentage of the Yakut and Balkan roots. In my pedigree there were no Italians and French at all, which killed my attempts to explain my love for wine.
The genetic bases of a not too wide range of diseases are well studied. For example, for diseases such as phenylketonuria, breast cancer, Bloom syndrome, hemochromatosis, and others, mutations are known that can cause them. The test shows whether you are a carrier of one of these mutations or not. Their presence can lead to serious risks of developing diseases. But mutations can also be “silent”, that is, manifest themselves only in the next generations. 23andMe gives the answer “is-no” for about fifty diseases. I found only one “silent” mutation that can lead to hemochromatosis - the accumulation of iron in the body. Judging by test 23andMe, there are no abnormalities in my genome. This may mean that my genome is clean. Or it may mean that other dangerous mutations have not yet been discovered by science.
If the genealogical and hereditary information looks very convincing, then I am skeptical about the risks and other tools of 23andMe.
23andMe has its own disease risk assessment system. This system covers both open research and databases, and their own results. Risk scores are sorted by decrease of 23andMe confidence in this result. Four stars of confidence means that the result is based on at least two studies in which at least 750 subjects were involved. Three or less confidence stars mean that the result is based on initial research on disease and mutations. The report on my genome does not differ in the abundance of diseases.
The risks are divided into three groups: increased, reduced and normal (average for the population) risk. If the risk assessment for the disease is higher than the average, then the disease falls into the high-risk group. You can see a description of each disease, how it threatens, and on the basis of what research an assessment of this risk was made. It also provides advice on what to do to reduce the risk of disease. Such tips are general in nature: play sports, do not eat a lot of salt, consult a doctor and so on.
In addition to health risk assessment, there are other 23andMe cognitive tools. Estimation based on stars of confidence is done on the absorption of certain medications. In my report, only drugs that I had never heard of were different with 4 stars of confidence: warfarin and abacavir. In another report, 23andMe tried to predict my external characteristics (eye color, tendency to baldness, etc.) according to my genomic data. The information in this report corresponded to reality by half. It was interesting to find out that my genome is 3% similar to the Neanderthal genome. Our ancestors interbred with Neanderthals, which left a mark on our genome. A tool to find relatives found some sixth brothers and sisters from the United States.
I have not found the formulas by which 23andMe risk assessments are calculated. Apparently, they are not published, as well as the test results database of 650 thousand of their clients. Therefore, I delved into the technical information to check how accurate the risk assessments are.
The disease with the highest risk in my report is venous thrombosis. Due to the increased density, blood can form a blood clot in the veins, which causes pain and prevents free blood flow. As a rule, blood accumulates in the veins of the legs. 23andMe reports that the average risk of developing this disease is about 12%, and my risk is about 36%.
The assessment of this risk is based on three mutations (identifiers rs6025, rs1799963 and rs505922). This information can be viewed in the technical report, for each mutation, a series of articles are presented with a study of the relationship between this mutation and the disease.
23andMe provides the ability to download raw data. The file contains all the mutations that have been tested at the client. I downloaded my file and opened it using the SNP Toolbox program. With this program you can see all the mutations and genes into which they fall, as well as look at the connection of mutations and diseases based on information from open sources. We remember that we get two different genomes - from mom and dad. The SNP Toolbox program showed that the first mutation has the CC genotype, that is, in this genome position in one version of this gene (for example, from mom) is C, and in another version (from dad) it is also C. Genotypes AG, AA, GG positively or negatively associated with venous thrombosis. The CC and GG in this case is the same genotype, since C and G are complementary nucleotides. According to open sources, the GG (CC) genotype does not cause the risk of venous thrombosis. The second mutation was indeed associated with venous thrombosis, but there is no numerical indicator of risk in open sources. The third mutation is in the noncoding part of the gene, and there are no known clinical studies on it. As it turned out, the information on the third mutation came from genome-wide association studies that are based on statistical data, and not on clinical trials.
Next, I looked at the publications from the 23andMe report. Basically, these were publications of the late 90s - early 2000s. These are studies in the so-called “pre-genomic” era - before the decryption of the human genome in the 2000th year. Among these publications there was only one large-scale study with 5.5 thousand subjects. This study is mentioned in the report on the first and second mutations, apparently, the system considers it as two different. The purpose of this study is to assess the risk of venous thrombosis in carriers of both of these mutations. However, in my genotype there is only one of them, that is, the results of this study do not apply to me.
I did not dig further, since the result was already enough to doubt the accuracy of 23andMe. Moreover, I still do not understand where the numerical values of these estimates come from.
Those who want to do 23andMe analysis now should know that the Food and Drug Administration (FDA) has banned the company. Trials are underway. The FDA believes that a program that advises clients on the basis of their genetic information is a medical device. And such devices must be certified. Because of the FDA ban, 23andMe's new customers only have access to genealogical information and raw data. So far, no information on health can be obtained.
Raw data 23andMe can work outside the company's website. For example, you can load them into the openSNP database, a project for collecting open access genomic data. It provides almost no useful information to the loader, but it helps scientists who study genomic variations. The site has already collected more than 1,000 test results.
Of the 21 sites that work with 23andMe data, I managed to launch only 2 on the go and for free.
The first of them showed that 4 mutations in my genome are somehow related to methylation. Of particular importance to me, this information is not.
The second site I managed to work with - Genes and Us , turned out to be much more interesting. From the 23andMe tests of two different people, the site displays the health risks of their possible offspring. Since I did not have the results of the second test, I tried to look at potential offspring with the unsuspecting Susan Smith - demo sample. It turned out that our potential offspring has an increased risk of developing venous thrombosis and prostate cancer. However, this result is based on two inaccurate estimates, so I don’t think that Susan Smith should be written off.
A year ago, I used the services of 23andMe - the world's largest company that provides genetic service directly to the client (direct-to-customer). Using the example of my result, I would like to tell you what lies behind such a genetic test.
Mutations
We will deal with the biological part of the issue. The human genome is a complete set of genetic information, which, for the most part, is packaged in 23 pairs of chromosomes. The human genome has an enormous volume of 3.2 billion pairs of DNA bases (A, C, G or T). It is as if all the people on the planet in pairs lined up in a strongly curved curve, and we have two such lines: from mom and dad. In addition, in each of the 3.7 trillion cells of our body, the genome is the same. That is, if in our
the genetic code has sneaked in some kind of change, it is not yet possible to "recode" it.
However, from a genetic point of view, all humans are twins, because the genomes of two people are 99.9% similar. At the same time, the differences are mainly represented by point mutations, when one nucleotide changes to another. Thus, several point mutations can distinguish a curly person from a person with straight hair, healthy from a cancer patient.
Unfortunately, we do not know as much as we would like, about the connection between the symbols of the genome and visible signs. This is due to the complexity and diversity of the mechanisms that occur in the cells. For a number of signs, this connection is well shown, for example, for such as blood type, eye color or susceptibility to breast cancer.
Mutations are bio-markers, which are targeted tests 23andMe and several other companies. Now their genetic test takes into account 1 million mutations in the genome. However, these are not all possible mutations. It is worth noting that there are tests that are aimed entirely at other markers. For example, paternity tests analyze short repeats of certain sections of DNA. These plots vary greatly between families, but are almost unchanged within the same family.
')
Process
In order to do a genetic test, you need to send a sample of your DNA. 23andMe and many other similar companies secrete DNA from saliva. It is worth noting that saliva is not the best material for DNA analysis, since the cells that it contains, like other somatic cells, can accumulate random mutations. I will not write what material and why is more suitable for DNA analysis.
The process is highly automated. You are sent a small box with a test tube, which you need to fill with saliva to the line. The test tube has a special nozzle to make it convenient to fill. When closing, the film on the nozzle is torn, and the tube is filled with the buffer solution so that the sample does not deteriorate on delivery. Then you seal it and ship it to the USA with DHL. You also need to enter a unique tube number on the 23andMe website, which will then match your DNA sample and your account. In semi-automatic mode, the bio-laboratory detects mutations and sends data to 23andMe. That is, the laboratory itself does not draw any conclusions, but only supplies raw data on mutations. The entire analysis is carried out by bioinformatics. The laboratory does not know the names either, but sees only the unique numbers of the test tubes. The result is ready about a month after sending the tube.
Test 23andMe can be ordered in almost all countries of the world, but not in Russia. Because in our country unauthorized shipping of biomaterial is illegal. There are known attempts to find loopholes in this system, but they either failed or ate too much time and nerves. I received and sent my test from Italy.
The cost of the test 23andMe is 99 dollars plus shipping. For residents and guests of the United States, delivery costs about $ 5, for Europeans it is about $ 60.
In large cities of Russia there are similar services and even 23andMe clones, but their prices are much higher, and the quality and volume of analyzes is still lower.
Ethics
Before you do genetic tests, you need to decide on ethical issues. First, genetic diseases are quite insidious, and many of them are still incurable. You can carry a mutation that can lead to phenylketonuria. You may not be sick with phenylketonuria, because a copy of the same gene from the other parent is normal, but your offspring may be susceptible to this disease. Or the test may show you that you have a very high risk of developing Alzheimer's disease. This disease is characterized by impaired mental activity and usually appears after 50 years. To live with or without such information is a purely individual question.
Secondly, genetic information is to some extent common to the whole family. That is, if you are a carrier of a mutation, then most likely it came from one of your parents and it will also be passed on to your descendants. And the test result will affect not only you, but the whole family.
Thirdly, individual genetic information is a new phenomenon, and so far it is not clear how to treat its confidentiality. 23andMe protects your data fairly well, but you can open it yourself. Undoubtedly, the more data we have in the public domain, the more power our statistical conclusions have. But who knows how it will be used in the future. For example, in America, even now genetic data may affect customer insurance rates.
Test result
23andMe site gives you a clear report on test results. Everything is convenient, systematic and simple.
I have identified 4 main categories of information received. The list is arranged in descending order of importance for me:
- Genealogical origin;
- Diseases and characteristics with a studied genetic basis: there is a mutation / no mutation;
- Risks assessed by the 23andMe analytical system;
- Cognitive.
Genealogical tests are based on large-scale studies of complete or partial genomes taken from different populations. Scientists were able to identify sets of mutations that are characteristic only for a given population (North Americans, Chinese, Australians, etc.). Having a set of mutations, you can determine which groups and in what percentage the person belongs to. Such tests have fairly good accuracy.
The graph shows my membership in the East European population. Since 23andMe does not work with Russia, the population closest to it is displayed. In principle, the result is true, because my parents are from Russia. It was interesting to find a small percentage of the Yakut and Balkan roots. In my pedigree there were no Italians and French at all, which killed my attempts to explain my love for wine.
The genetic bases of a not too wide range of diseases are well studied. For example, for diseases such as phenylketonuria, breast cancer, Bloom syndrome, hemochromatosis, and others, mutations are known that can cause them. The test shows whether you are a carrier of one of these mutations or not. Their presence can lead to serious risks of developing diseases. But mutations can also be “silent”, that is, manifest themselves only in the next generations. 23andMe gives the answer “is-no” for about fifty diseases. I found only one “silent” mutation that can lead to hemochromatosis - the accumulation of iron in the body. Judging by test 23andMe, there are no abnormalities in my genome. This may mean that my genome is clean. Or it may mean that other dangerous mutations have not yet been discovered by science.
If the genealogical and hereditary information looks very convincing, then I am skeptical about the risks and other tools of 23andMe.
23andMe has its own disease risk assessment system. This system covers both open research and databases, and their own results. Risk scores are sorted by decrease of 23andMe confidence in this result. Four stars of confidence means that the result is based on at least two studies in which at least 750 subjects were involved. Three or less confidence stars mean that the result is based on initial research on disease and mutations. The report on my genome does not differ in the abundance of diseases.
The risks are divided into three groups: increased, reduced and normal (average for the population) risk. If the risk assessment for the disease is higher than the average, then the disease falls into the high-risk group. You can see a description of each disease, how it threatens, and on the basis of what research an assessment of this risk was made. It also provides advice on what to do to reduce the risk of disease. Such tips are general in nature: play sports, do not eat a lot of salt, consult a doctor and so on.
In addition to health risk assessment, there are other 23andMe cognitive tools. Estimation based on stars of confidence is done on the absorption of certain medications. In my report, only drugs that I had never heard of were different with 4 stars of confidence: warfarin and abacavir. In another report, 23andMe tried to predict my external characteristics (eye color, tendency to baldness, etc.) according to my genomic data. The information in this report corresponded to reality by half. It was interesting to find out that my genome is 3% similar to the Neanderthal genome. Our ancestors interbred with Neanderthals, which left a mark on our genome. A tool to find relatives found some sixth brothers and sisters from the United States.
Own analysis
I have not found the formulas by which 23andMe risk assessments are calculated. Apparently, they are not published, as well as the test results database of 650 thousand of their clients. Therefore, I delved into the technical information to check how accurate the risk assessments are.
The disease with the highest risk in my report is venous thrombosis. Due to the increased density, blood can form a blood clot in the veins, which causes pain and prevents free blood flow. As a rule, blood accumulates in the veins of the legs. 23andMe reports that the average risk of developing this disease is about 12%, and my risk is about 36%.
The assessment of this risk is based on three mutations (identifiers rs6025, rs1799963 and rs505922). This information can be viewed in the technical report, for each mutation, a series of articles are presented with a study of the relationship between this mutation and the disease.
23andMe provides the ability to download raw data. The file contains all the mutations that have been tested at the client. I downloaded my file and opened it using the SNP Toolbox program. With this program you can see all the mutations and genes into which they fall, as well as look at the connection of mutations and diseases based on information from open sources. We remember that we get two different genomes - from mom and dad. The SNP Toolbox program showed that the first mutation has the CC genotype, that is, in this genome position in one version of this gene (for example, from mom) is C, and in another version (from dad) it is also C. Genotypes AG, AA, GG positively or negatively associated with venous thrombosis. The CC and GG in this case is the same genotype, since C and G are complementary nucleotides. According to open sources, the GG (CC) genotype does not cause the risk of venous thrombosis. The second mutation was indeed associated with venous thrombosis, but there is no numerical indicator of risk in open sources. The third mutation is in the noncoding part of the gene, and there are no known clinical studies on it. As it turned out, the information on the third mutation came from genome-wide association studies that are based on statistical data, and not on clinical trials.
Next, I looked at the publications from the 23andMe report. Basically, these were publications of the late 90s - early 2000s. These are studies in the so-called “pre-genomic” era - before the decryption of the human genome in the 2000th year. Among these publications there was only one large-scale study with 5.5 thousand subjects. This study is mentioned in the report on the first and second mutations, apparently, the system considers it as two different. The purpose of this study is to assess the risk of venous thrombosis in carriers of both of these mutations. However, in my genotype there is only one of them, that is, the results of this study do not apply to me.
I did not dig further, since the result was already enough to doubt the accuracy of 23andMe. Moreover, I still do not understand where the numerical values of these estimates come from.
FDA
Those who want to do 23andMe analysis now should know that the Food and Drug Administration (FDA) has banned the company. Trials are underway. The FDA believes that a program that advises clients on the basis of their genetic information is a medical device. And such devices must be certified. Because of the FDA ban, 23andMe's new customers only have access to genealogical information and raw data. So far, no information on health can be obtained.
Other sites
Raw data 23andMe can work outside the company's website. For example, you can load them into the openSNP database, a project for collecting open access genomic data. It provides almost no useful information to the loader, but it helps scientists who study genomic variations. The site has already collected more than 1,000 test results.
Of the 21 sites that work with 23andMe data, I managed to launch only 2 on the go and for free.
The first of them showed that 4 mutations in my genome are somehow related to methylation. Of particular importance to me, this information is not.
The second site I managed to work with - Genes and Us , turned out to be much more interesting. From the 23andMe tests of two different people, the site displays the health risks of their possible offspring. Since I did not have the results of the second test, I tried to look at potential offspring with the unsuspecting Susan Smith - demo sample. It turned out that our potential offspring has an increased risk of developing venous thrombosis and prostate cancer. However, this result is based on two inaccurate estimates, so I don’t think that Susan Smith should be written off.
Source: https://habr.com/ru/post/231591/
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