DNA – Crack the Code by Nyla

Protecting Our Personal Information.

In 2008, President George W. Bush signed into law the nearly unanimously approved Genetic Information Nondiscrimination Act of 2008 (GINA). This law is meant to prevent discrimination in employment and health insurance based on genetic information. The law effectively prevents group health plans and employers from requesting that individuals undergo genetic tests, thereby protecting what many view as basic human rights: healthcare and equal employment opportunity. While the GINA of 2008 prevents the use of genetic information with health insurance, it does not prevent the use of genetic testing in other arenas, such as life insurance.

Life Insurance: A Product in a Competitive Market.

With life insurance, an insurer agrees to pay a designated amount of money in response to the death of the policy holder. In return, the policy holder must pay a premium in regular intervals throughout the course of the policy. Accordingly, the insurance company charges a premium based upon a detailed underwriting and actuarial process.

Mortality rates for different age groups are used in determining an individual’s premium. For instance, it is predicted that 0.35 in 1000 non-smoking 25 years old males will die in the first year of policy coverage. This allows the insurance company to charge premiums to a group of individuals given an expected number of deaths and payouts.

Individual life insurance premiums are determined in an underwriting process. During this process, age, health, and tobacco use are the major factors that play into premium determination. However, more detailed questions about the health and lifestyle of the client are often asked to make a better judgement what type of premium would be required for that person. For older applicants, paramedical professionals are sent to perform more detailed tests including blood and urine tests.

What are they looking for in the blood test? Right now, the blood test screens for the presence of antigens to the HIV  virus, hepatitis, evidence for liver or kidney disorders, and certain types of autoimmune diseases. These are all increased risk factors for mortality. A positive test for one or more of these indicators may result in higher premiums or denial of coverage.

Enter genetic testing.

The blood test performed by the paramedic is all that would be required for a complete genome scan. This type of test can detect predispositions to over 100 complex genetic diseases such as Alzheimer’s Disease, Parkinson’s Disease, Heart Disease, and many different types of cancers. What would happen if insurance companies used genetic information in the underwriting process?

Genetic information will add an array of new dimensions to the current underwriting process as it allows insurers to account for a plethora of diseases beyond a typical life insurance exam. Moreover, a genetic test can show increased risk, normal risk or decreased risk for a particular disease. It is possible that this information may improve the likelihood of coverage and/or lower premiums for individuals.

The use of genetic information may be a disgusting thought in some peoples’ minds, but we must consider what happens if we ban the use of genetic information in life insurance. An individual may always get himself tested. What if a 50 year old male learns that he has an increased risk for three different late onset genetic disorders and decides to take out a large policy anticipating this decline. This “moral hazard” will cause the insurance company to charge a lower premium than what is actuarially fair, and it will begin to lose money for every individual that engages in this behavior. Eventually, it will prevent the proper functionality of the life insurance company, and it will disadvantage everyone who seeks to take out a life insurance policy.

To Know or Not to Know? That is the Question.

There are two issues at play with life insurance and genetic testing: protection of personal data, and avoiding a situation where there is asymmetry of information. If the consumer knows of a predisposition and the insurer does not, the consumer has the power to take out a policy at an actuarial loss to the insurer. However, some may believe that the insurer should not ever know about the consumer’s genetic information because that is both private and immutable material. What is the optimal solution here?

One solution would be to ban genetic testing altogether. We might decide not to let the consumer or the insurer employ this technology. I think this would be terrible. We would be taking several steps backwards if we decided to ban genetic testing.

Another solution is for knowledge to be spread all around. Life insurers should be allowed to use genetic information as long as the consumer is made aware of the results. This way, there is no asymmetry of information. Let’s not forget that genetic testing could even reveal a genetic protection against certain diseases (lower than average risk).

I do not believe that applying genetic testing towards life insurance is a violation of privacy or human rights. Life insurance is not a societal right. It is a product that consumers have the option of buying. If a consumer does not want to have their genes tested, then perhaps they should reconsider taking out a life insurance policy.

Photo by: liber

So I’ve already written a post about the challenges of phasing genotype data, but now I’m here to help you accomplish that task. Let’s go through a checklist of what will be needed:

• Your personal SNP information (through either 23andMe, Navigenics, deCODEme, etc.)
• The SNP information for your parents (preferably through the same company/microarray platform)

If you want to use my specific method you also need:

• The most recent Java Runtime Environment.

Of course, you can implement your own version of this phasing protocol with basic familiarity in a programming language or (more tediously) with some macros and if statements in Microsoft Excel.

How to Phase Your Genome: A Conceptual Overview

With information from both parents, it is possible to phase your genome (for the vast majority of SNP calls). We rely on the fact that for most situations, you can identify exactly what was inherited from your father and exactly what was inherited from your mother.

For example: If at a particular position, your genotype call is AT, your father’s genotype call is AA, and your mother’s genotype call is TT, then you know that the A must have come from your father, and the T must have come from your mother. Simple! We will refer to situations where phase can be determined as informative.

The chart to the right outlines exactly which situations are informative. The good news is that every situation is informative with the exception of one: when both parents and the child are heterozygous. Here, we are unable to say for certain what allele was inherited from each parent.

A sample implementation of how to phase a child’s DNA is illustrated below:

Implementing this Phasing Strategy: I’m Here to Help

If you have all the files mentioned above and would like to phase your genome, then I am more than happy to provide you with a Java archive that will allow you to accomplish this task. Even more, I will provide detailed instructions as to how to use this archive (it’s really simple, I swear).

You can download the Java program here as a zip file. Once finished, unzip the contents into the same fold. You should see Launcher.jar and PhaseME.jar. To launch the program, click Launcher.jar (I thought that was pretty obvious), and the GUI pictured below should appear:

The input files need to contain four columns in this order: rsid, chromosome, position, genotype. The genotype data needs to simply be AA,  AT, TT, etc. without any slashes or quotation marks.

Before running the program, you do need to make sure that your data is the same length and contains the same SNPs between both parents and the child. I have not incorporated any checks into the program for this. My recommendation is to use an IF statement in Microsoft Excel (version 2007) to make sure that all three files line up. Also, make sure that only one row of headers exists in the files.

Finally, select the files to be compared (father, mother, child), and select an output location and choose a name for the outputs. There will be 23 outputs with the following filenames: <yourchosenname>.chr<chromosome>.phased.txt. Each chromosome has its own output that shows you the haplotype inherited from the father and the haplotype inherited from the mother. This program just ignores Y and MT data. However, the program does have the ability to recognize whether the child is male or female, and it assigns the X chromosome haplotypes accordingly.

Let me know about any problems with the program (ex. If it does not produce any output), and I will check to see (1. If your input files are the problem, 2. If the program is the problem).

You might be genetically inclined to get buzzed from drinking less. A study published on December 8th by researchers from the Earnest Gallo Clinic and Research Center indicates that the SNP rs1051730, is linked to a gene that affects how much alcohol you need to get buzzed.

The study is kind of funny. Participants were subjected to a “10 am 3 drink challenge,” and body sway was measured afterward. It was found that those homozygous for cytosine (C) at this particular locus responded quicker to the alcohol than did those homozygous for thymine (T). In fact, those who responded slower to alcohol (T individuals) were at a higher long-term risk to alcohol abuse.

What does this mean for me? For one thing, I could screen all of my dates in order to determine who would be the cheapest to take out drinking. More importantly, I could choose which combination to give my kid: do I prepare him to be the ultimate binge drinker in college by giving him two copies of the T gene? Or do I lower his risk for alcoholism by giving him two C’s, making him a lush? Such questions are going to plague me in my quest to build the perfect child.

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It’s been all over the news lately that companies are beginning to test peoples’ genes in order to determine whether or not they are predisposed to certain diseases or traits. Atlas Sports Genetics has recently offered a test to determine whether or not a child will be the next olympic gold medalist.

I’ll start by saying that genes do not determine everything. However, they can set limits or give advantages. In testing whether or not a child is athletic, Atlas Sports Genetics is actually testing to see what variation of the ACTN3 gene, which is involved in muscle contractions. One version of the gene has an association with sprint athletes, while the other version of the gene was not seen in these athletes. It is true, the test may prove to be quite telling for these children.

While I am supportive of using this information, I would never use Atlas Sports Genetics. The particular method of testing for this ACTN3 gene involves determining which single nucleotide polymorphism (SNP) your child has at position 66,084,671 of his or her 11th chromosome. Being that there are two copies of the gene, you are actually looking for two polymorphisms. The particular polymorphism is called rs1815739. A detail record of this SNP can be found on SNPedia (along with literally millions of other SNPs).

My problem with Atlas Sports Genetics is that they are charging $150 to test one SNP when you can pay $250 more at 23andMe to get 500,000 SNPs tested. That’s a half of a tenth of a penny more for each extra SNP. Instead of finding out whether or not you have a version of a gene that tenuously suggests you will be a better sprinter, you can also find out whether or not you are predisposed to autism, alzheimers, depression, or other such illnesses. The data from the 23andMe test is so powerful, you can even trace where and when your genes came from.

Even with a positive result from Atlas Sports Genetics, unless you keep your kid away from too much McDonald’s and on a steady diet of your dreams for the gold, he’s probably not going to the olympics. I wouldn’t say that it’s a bad test or a waste of time, but when the service is more cost efficient elsewhere, I can’t keep my mouth shut.

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