Chris Rock
Interdisciplinary Paper Introduction
Newborn Screening
The ethical question that I will be considering in this paper is whether we can ethically screen for the ACTN3 gene, which is linked to determining what type of athletic ability the child will have, in our newborn children. Based on traditional criteria meant for disease screening that I have modified to pertain to traits, I will argue that our newfound ability to screen for genes that are directly linked to various traits, like athletic ability, is ethically permissible.
Thanks to Robert Guthrie’s discovery of a bacterial assay that could screen for
Phenylketonuria in the early 1960s, babies born in the United States have had their heels pricked for a drop of blood for almost fifty years. Phenylketonuria is an autosomal recessive metabolic disorder caused by a mutation on chromosome twelve. The mutation hinders the ability of the phenylalanine hydroxylase enzyme to hydrolyze phenylalanine into tyrosine, resulting in a buildup of phenylalanine. When in the womb, this is not a problem for the baby because the mother’s phenylalanine hydroxylase is able to hydrolyze both her and her baby’s phenylalanine. However, when the baby no longer has access to the mother’s working enzyme, excess phenylalanine during the growth of the nervous system results in mental retardation.
The good news about this disease is that it is easy and inexpensive to treat. By limiting the amount of phenylalanine in the child’s diet, the excess phenylalanine and, therefore, mental retardation do not occur. Even better news is that this strict diet is not life-long. According to the Nelson Essentials of Pediatrics, this diet only needs to be meticulously followed until around the age of ten at which age the diet can be more lenient of phenylalanine (1).

Robert Guthrie’s discovery of the bacterial assay to identify Phenylketonuria did not stop at just this debilitating metabolic disease. Galactosemia, a deficiency in one of three enzymes needed to convert galactose into glucose (2), Maple Syrup Urine Disease, a metabolic disorder causing the inability to break down leucine, isoleucine, and valine (3), and
Homocystinuria, a deficiency in the cystathionine beta synthase (4), were all being tested for in the late 1960’s via the same drop of blood that the Phenylketonuria bacterial assay used.
Scientists and doctors alike were not satisfied with just these four disorders, however. The next two diseases that tests were found for were Congenital Hypothyroidism, a thyroid hormone deficiency (5), in the 1970’s and Sickle Cell anemia, an abnormal hemoglobin that causes pain and sometimes death, in the 1980’s (6). One of the key similarities in all of these disorders is that they have treatments. This was huge when it came to determining whether or not to screen newborns for it.
With technology advancing exponentially, many people realized that there needed to be a set of standards to determine whether or not a given disease should be screened for in newborns. In the 1968 World Health Organization monograph, James Wilson and Gunnar
Jungner published the following 10 criteria that needed to be met in order to include a disease in a screening program:
1) The condition sought should be an important health problem
2) There should be an accepted treatment for patients with recognized disease
3) Facilities for diagnosis and treatment should be available
4) There should be a recognizable latent or early symptomatic stage
5) There should be a suitable test or examination
6) The test should be acceptable to the population

7) The natural history of the condition, including development from latent to declared disease, should be adequately understood
8) There should be an agreed policy on whom to treat as patients
9) The cost of case-finding (including diagnosis and treatment of patients diagnosed) should be economically balanced in relation to possible expenditure on medical care as a whole
10) Case-finding should be a continuing process and not a “once and for all project”
From this list, Wilson and Jungner agreed that, “of all the criteria that a screening test should fulfill, the ability to treat the condition adequately, when discovered, is perhaps the most
important.”(6)
Until recently, newborn screening programs greatly varied from state to state. Each state had their own set of standards to evaluate whether a condition should be screened for or not. Although Wilson and Jungner’s set of criteria had an influence on states’ decisions, there was no nationwide standard. In 2005, the American College of Medical Genetics was appointed by the Maternal and Child Health Bureau to develop a set of guidelines that states could use as a basis for their genetic screening program (7). The American College of Medical Genetics formulated an algorithm that is very similar to the exercise that we did in class when first learning about utilitarianism. In developing this algorithm, the American College of Medical
Genetics used a utilitarian style approach with the intention that it “delivers the greatest good to the greatest number of people”. They took factors such as incidence of condition, burden of disease, whether a sensitive and specific identifying test is available, availability and cost of treatment, benefits of early identification and intervention, and simplicity of treatment and gave them a numerical value. If the final score of the given disease was over 1200, the disease

was placed on the core panel list which is a list of diseases that testing should be mandatory for
(8).
The reason the American College of Medical Genetics and the Maternal and Child Health
Bureau went through all of the meticulous work of surveying and analyzing data of genetic conditions was, ultimately, to ensure that everyone nationwide experienced the benefits of genetic testing in newborns. The main benefit of newborn genetic testing is early identification of a disorder that, like Phenylketonuria, Galactosemia, Maple Syrup Urine Disease,
Homocystinuria, and Sickle Cell anemia, immediately affects the child but has a treatment.
Without this early treatment, the disease would already begin to harm the child. Genetic testing can also take into account the pharmacogenetics, inherited variations in responding to different medicines (9), and nutrigentics, variations corresponding to diet and health (10), that everyone has. Essentially, it is a personalized medical treatment plan. Potential research subjects and benefits to families concerning reproduction are also benefits of newborn genetic screening (11).
One of the main differences between the genes that are linked to the previously mentioned diseases and the ACTN3 gene is that the ACTN3 gene is linked to a trait, not a disease. The trait it is linked to is athletic ability. Therefore, Wilson and Jungner’s criteria, pertaining to diseases, need to be modified. From class discussions and relevant literature, I have adapted their criteria into the following criteria that are applicable to traits:
1) The trait needs to relate to a significant personal characteristic
2) The information obtained from the test should be useful and beneficial
3) The test should be both sensitive and specific

4) The test should yield clear, unambiguous results
5) Stigmatization and discrimination should not be consequences of the test results
6) Informed consent needs to be given
7) The test should be inexpensive
8) The test should be a fair allocation of healthcare resources
9) The results should be used as a way to benefit the patient and not as a way to achieve a goal
The first criterion is supported by the ethical principles of nonmaleficence, distributive justice and utilitarianism. If the trait is not a significant characteristic, there is no point in testing for it. Although the test itself is not overly invasive, there is no reason to put someone at physical or mental risk if there is no significance to the characteristic. Along with that, if the trait in no way affects others that are near the person with this trait, there is no sense in spending the precious time of the technicians running the test or money of those paying for the test.
The second criterion is reinforced by the ethical principle of beneficence. The information that you obtained from the test needs to have some beneficial use or, again, there is no reason to take the test.
The third, fourth, and fifth criterion all are supported by the ethical principle of nonmaleficence. If the person cannot understand the results from the test or if the test indicates one thing but the patient is, in fact, the opposite, then harm or, at the minimum, a lack of beneficial outcomes may result from taking the test. Furthermore, if the information obtained from the test is going to result in stigmatization or discrimination, this can also bring about harm to the person being tested.

The sixth criterion is influenced by the ethical principle of autonomy. The person being tested has the right to decide his or her own fate. He or she should not have to undergo the testing if he or she so chooses.
The seventh and eighth criteria are supported by the ethical principle of justice. Even if the healthcare system is not paying for the testing, it still takes experts and technicians’ limited time and effort to run the test.
The last criterion is influenced by Kant’s end-in-itself categorical imperative. The results of the test should be put to good use to benefit the patient. They should not, in the case of the
ACTN3 gene, be used as a way to, in essence, sell your child’s athletic abilities to the highest bidder.
Although one of the main benefits of genetic screening is personalized medicine, a personalized workout plan is not typically thought to come from genetic testing. However, the scientists at Atlas Sports Genetics, one of the leading companies involved in predicting athleticism using genetics, insist that testing for the ACTN3 gene can determine “training and conditioning programs necessary for athletic and sport development,” (12).
Certain alleles of the ACTN3 gene are linked to certain types of activity. According to
Atlas Sports Genetics, being homozygous for the R577X allele is linked to an aptitude towards endurance events. If you are homozygous for the 577R allele, you are supposed to excel at power and sprint activities. People who are heterozygous for the R577X and 577R allele have a predisposition for endurance activities as well as sprint and power events (12).

The ACTN3 gene is located on the long arm of chromosome eleven (13), and it consists of 2,858 nucleotides (14). The ACTN3 gene produces alpha-actinin 3, a protein found only in fast twitch muscle fibers, which helps stabilize the thin, actin filaments (15) via the calponin homology domain (16).
Fast and slow twitch muscles contract in the same way. Calcium, released from the sarcoplasmic reticulum, binds to troponin which is bound to tropomyosin. Tropomyosin is a complex of proteins that separates actinin and myosin. When the calcium binds to the troponin, a conformational change occurs in the tropomyosin molecule which allows actin to bind to myosin. The myosin cross-bridge then pulls the actin filaments, resulting in the muscle contracting (17).
The larger fast twitch muscle fibers are stabilized due to the alpha-actinin 3 protein produced from the ACTN3 gene. The more stable the muscle fibers are, the faster and stronger the contraction is (17). This is why the fast twitch muscles, especially the ones that are stabilized from the alpha-actinin 3 protein, are more crucial than slow twitch muscles for events such as sprinting and power lifting.
The ACTN3 gene is linked to more than just athletic ability though. Jane Seto et al. tested mice of different ages that had their ACTN3 gene inhibited, knocked out. What they found was alpha-actinin 3 deficient individuals, those homozygous for the R577X allele, may experience faster decline in muscle function with increasing age (18). However, Carmen Fiuza-
Luces et al. discovered opposing results. Carmen Fiuza-Luces et al. compared the genotypes of centenarians with those of elite endurance and power athletes. Their tests showed that the

genotype of the centenarians was similar to that of the endurance athletes’ genotype, homozygous for R577X (19). These tests indicate that the environment, which will be discussed later in the paper, plays a role in the type of athletic ability you will have and how long you will live.
Atlas Sports Genetics’ claim that athletic ability can be predicted by a single gene is not entirely false. Tests have shown that the 577R allele is much more frequent in both male and female elite sprint athletes. This test also revealed that, among the female endurance athletes, the R577X allele was much more common than it was in the normal population. However, the same results did not occur in males suggesting that the ACTN3 gene affects genders differently
(20). Another test, done on elite bodybuilders, found a significantly lower frequency in the bodybuilders for being homozygous for the R577X allele than in the control group (21).
The difference between the 577R allele and the R577X allele is that on the R577X allele, at position 1,747 on the gene, a polymorphism converting cytosine into thymine occurs. This transition mutation causes an arginine to be replaced by a stop codon at residue 577 of the alpha-actinin protein (22).
In order to identify which allele you have, a process known as restriction fragment length polymorphism is performed. This method utilizes a fragment of DNA with restriction enzyme cut sites on each end with a target DNA sequence between these two cut sites. The target sequence binds to a primer, a specific sequence of single stranded DNA (23). In the case of the ACTN3 gene, the different alleles can be identified based on weight after running a gel electrophoresis. The reason that the two alleles are different in weight is because the transition

mutation at site 1,747 on the gene forms a Ddel restriction enzyme cut site. This causes a single fragment of DNA to be cut into two pieces. The resulting products of the R577X allele are fragments consisting of 108, 97, and 86 base pairs while the 577R allele’s products are 205 and
85 base pairs long (24). Therefore, the results of the test would show three bands for the R577X allele and only two bands for the 577R allele.
Using the restriction fragment length polymorphism technique is both accurate and efficient. It allows you to tell if the person is homozygous for either allele or if they are heterozygous by counting the number of bands on the gel. Also, Atlas Sports Genetics is selling a home test kit for the $169 (12) which, in the world of healthcare, is very inexpensive.
Therefore, due to the accuracy, clear results, and relatively low cost of the test, criterion three, four, and seven of the modified criteria are met, respectively.
Although genetic testing does show a greater frequency of being homozygous for the
577R allele in world class sprint and power athletes and a greater frequency of being homozygous for the R577X allele in elite endurance athletes, the test does not guarantee these results. Yannis Pitsiladis, a biologist from the University of Glasgow (25), screened Colin
Jackson, a former world-record holder in the 110-meter hurdles, for ACTN3. What he found was not shocking. “"He had the right version," Pitsiladis told to Sports Illustrated, "but so do I,"(26).
This goes to show that just because someone has the correct allele to be a superior athlete does not mean that greatness is guaranteed to them. Also, just because you do not have the
‘ideal’ genotype for a particular sport does not mean that you will not excel in that sport. In the same Sports Illustrated article, two examples were given, one of a Jamaican sprinter and one of

a Spanish long-jumper, where the athlete had the ‘wrong’ allele, R577X, for his or her given sport (26).
Although the results of the test indicating which allele you have may be clear, what they mean can remain uncertain. Scientists remain unsure as to what degree the genotype will influences how much better you will be at the sporting events you have a predisposition for than someone who does not have a predisposition for. This suggests that the environment plays a role in determining athletic ability. Ericcson et al. did a study on elite and non-elite musicians. What they found distinguishing the two groups was the hours of deliberate practice each musician did. The study also discovered that practice and performance is a positive, linear relationship (27).
North et al. concluded that, since approximately 16% of the world’s population is homozygous for the R577X allele, the ACTN3 gene is a non-essential gene (28). Since this gene and its mutated allele, R577X, are neither essential nor linked to significant characteristics such as violence, alcoholism, or compulsive lying, the first criterion in the modified criteria is not validated.
Knowing which allele you have can prove to be useful. This knowledge can give you insight on the types of workouts that would be most beneficial to you. If you see results from your workouts in a relatively short time period, you are more likely to stay motivated and continue to work hard. This means that you will be more likely to continue exercising which, according to many experts such as the Mayo Clinic, is very beneficial to your health (29).
Another benefit of knowing which allele you have is that you know which sport you have a

predisposition for. This will allow you to focus on the sports that you most likely will be good at.
Although this may seem minor to some, participating in sports that you are likely to be good at may reduce the risk of being made fun of for not being good at the sport. Therefore, the second criterion of the modified criteria for traits is met.
A downside to testing for the ACTN3 gene is that stigmatization and discrimination may occur. Children might form groups with people of the same ACTN3 genotype and exclude those with a different genotype. However, when we think about stigmatization and discrimination when dealing with genetics, we typically worry about insurance companies and employees performing these acts. Since the ACTN3 gene is linked to a positive behavioral trait, I do not think stigmatization and discrimination will occur. Therefore, the fifth criterion of the modified criteria is met.
On Atlas Sport Genetics’ website, testimonials can be found. The very first testimonial listed reads:
“Atlas Sports Genetics testing was very informative and the process was quite simple.
Although, my daughter is only 9 she now knows that she had the Sprint, Power, &
Strength advantage which we can use to market her Athletic Career and hopefully a wonderful scholarship from this process.” (12)
To me, this sounds as though this young girl will be forced into playing sports that require sprint, power, and strength abilities. It also sounds as though this parent is looking to use the results as a way to sell the daughter to the college that will pay the most money. This would clearly violate the ninth criterion. However, we cannot use this one testimonial, which could simply be a poor representation of the parent’s intentions, as a way to describe everyone’s

intentions. This is a very tough criterion to meet because each individual case is different. There simply is no way to be completely sure of what the intentions are of every single parent.
Therefore, the parents must take it upon themselves to thoroughly evaluate their own intentions and make sure it is for the best of their child.
Since society’s money will not be spent on testing for the ACTN3 gene, money is, essentially, not an issue here. However, I do think the time and effort that the test for this trait will consume needs to be considered. In the classroom discussions, we have established that the amount of genetic studies is exponentially increasing each day. This, in turn, should mean that the laboratories that run the tests are very busy. Since we are testing for a non-significant characteristic trait and not a disease, I do not believe that we can validate testing for this trait before testing for diseases. However, if the laboratories are not as busy as we have made them seem or if the laboratories that are testing for this trait only test for traits and not diseases, then I believe that the eighth criterion of the modified criteria is met.
In testing for the ACTN3 gene, young children may be pressured or feel obligated to participate in activities that they do not want to participate in. This would be in violation of autonomy. However, not allowing them to be tested is also in violation of their autonomy. In order to make sure the autonomy of the child is maintained, I believe that both parents and children should be fully educated on their decision. This way everyone is clear of what the results will say and what the potential effects are. If this occurs, then criterion six of the criteria pertaining to traits is met.

Since it is not mandatory, patients’ autonomy will not be violated. The results can be put to good use such as personalizing workouts and focusing on what sports you will be good at. As for other children forming groups and excluding others based on genotypes, if the genotypes were not known, children would find another factor to form exclusive groups. As long as the intentions of everyone are for the good of the patient, and everyone is well educated on what the results indicate, I believe that it is ethically permissible to test for the ACTN3 gene in our children.

Works Cited
1) Kliegman, Robert M., Hal B. Jenson, Karen J. Marcdante, Richard Elliot Behrman, and Waldo
Emerson Nelson. Nelson Essentials of Pediatrics. Philadelphia, PA.: Elsevier
Saunders, 2006. 225. Web. 23 Oct. 2011.
2) "Galactosemia - Genetics Home Reference." Genetics Home Reference - Your Guide to
Understanding Genetic Conditions. U.S. National Library of Medicine, 17 Oct. 2011. Web.
24 Oct. 2011. <http://ghr.nlm.nih.gov/condition/galactosemia>.
3) "Maple Syrup Urine Disease: MedlinePlus Medical Encyclopedia." National Library of
Medicine - National Institutes of Health. U.S. National Library of Medicine, 15 May 2011.
Web. 24 Oct. 2011. <http://www.nlm.nih.gov/medlineplus/ency/article/000373.htm>.
4) Kniffin, Cassandra L. "Homocystinuria Due to Cystathionine Beta-Synthase
Deficiency."OMIM - Online Mendelian Inheritance in Man. 11 Oct. 2011. Web. 24 Oct.
2011. <http://omim.org/entry/236200>.
5) "Congenital Hypothyroidism - Genetics Home Reference." Genetics Home Reference - Your
Guide to Understanding Genetic Conditions. U.S. National Library of Medicine, 17 Oct.
2011. Web. 24 Oct. 2011. <http://ghr.nlm.nih.gov/condition/congenitalhypothyroidism>.
6) Valverde, Carlos. Genetic Screening of Newborns: an Ethical Inquiry. New York: Nova
Science, 2010. Print.
7) Buchbinder, Mara, and Stefan Timmermans. "Medical Technologies and the Dream of the
Perfect Newborn." Medical Anthropology, Vol 30(1), Jan, 2011. Pp. 56-80 30.1 (2011):
56-80. Print.
8) "American College of Medical Genetics Newborn Screening Expert Group. Newborn
Screening: Toward a Uniform Screening Panel and System--Executive Summary.
PEDIATRICS 2006;117:S296-S307." Pediatrics 118.2 (2006): 851. Print.
9) "ONE SIZE DOES NOT FIT ALL: THE PROMISE OF PHARMACOGENOMICS."Pharmacogenomics
Factsheet. 31 Mar. 2004. Web. 25 Oct. 2011.
<http://www.ncbi.nlm.nih.gov/About/primer/pharm.html>.

10) Simopoulos, Artemis P. "Nutrigenetics/Nutrigenomics." Annual Review of Public Health31.1
(2010): 53-68. 4 Jan. 2010. Web. 25 Oct. 2011.
<http://www.annualreviews.org/doi/abs/10.1146/annurev.publhealth.031809.130844?j
ournalCode=publhealth>.
11) Baily, Mary Ann, and Thomas H. Murray. "Ethics, Evidence, and Cost in Newborn
Screening." Hastings Center Report 38.3 (2008): 23-31. May-June 2008. Web. 25 Oct.
2011.
<http://www.thehastingscenter.org/pdf/hcr_2008_may_jun_early_release1.pdf?src=bai lymurraypdf>.
12) Atlas First SportGene® Test. Web. 25 Oct. 2011. <https://www.atlasgene.com/>.
13) "OMIM Entry - 102574 - ACTININ, ALPHA-3." OMIM - Online Mendelian Inheritance in Man.
Web. 25 Oct. 2011. <http://omim.org/entry/102574>.
14) "Alpha Actinin 3." Homo Sapiens Alpha Actinin 3. National Center for Biotechnology
Information. Web. 25 Oct. 2011. <http://www.ncbi.nlm.nih.gov/nuccore/M86407?>.
15) "ACTN3 Actinin, Alpha 3 [ Homo Sapiens ]." ACTN3 Actinin, Alpha 3 [ Homo Sapiens ] - Gene
- NCBI. Web. 25 Oct. 2011. <http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene>.
16) Castresana, J. "Does Vav Bind to F-actin through a CH Domain?" FEBS Letters 374.2 (1995):
149-51. 12 Sept. 1995. Web. 25 Oct. 2011.
<http://www.sciencedirect.com/science?_ob=MiamiImageURL&_cid=271102&_user=73
49611&_pii=001457939501098Y&_check=y&_origin=&_coverDate=30-Oct-
1995&view=c&wchp=dGLzVlS-zSkzk&md5=470695387f2fbe4de4eb740b4b65fb77/1s2.0-001457939501098Y-main.pdf>.
17) Housh, Terry J., Dona J. Housh, and Herbert A. DeVries. Applied Exercise & Sport Physiology.
Scottsdale, AZ: Holcomb Hathaway, 2006. Print.
18) Seto, Jane T., Stephen Chan, Nigel Turner, Daniel G. MacArthur, Joanna M. Raftery, Yemima
D. Berman, Kate G.R. Quinlan, Gregory J. Cooney, Stewart Head, Nan Yang, and Kathryn
N. North. "The Effect of α-actinin-3 Deficiency on Muscle Aging."Experimental
Gerontology 46.4 (2011): 292-302. Web. 19 Nov. 2011.
<http://web.ebscohost.com/ehost/detail?sid=ce1f6adc-0e22-4bb7-a5c4-

8faeb7048306%40sessionmgr114&vid=1&hid=112&bdata=JnNpdGU9ZWhvc3QtbGl2ZQ
%3d%3d#db=a9h&AN=59455306>.
19) Fiuza-Luces C, Ruiz JR, Rodríguez-Romo G, Santiago C, Gómez-Gallego F, et al. (2011) Are
‘Endurance’ Alleles ‘Survival’ Alleles? Insights from the ACTN3 R577X Polymorphism.
PLoS ONE 6(3): e17558. doi:10.1371/journal.pone.0017558
20) Yang, N., MacArthur, D. G., Gulbin, J. P., Hahn, A. G., Beggs, A. H., Easteal, S., North,
K. ACTN3 genotype is associated with human elite athletic performance. Am. J. Hum.
Genet. 73: 627-631, 2003.
21) Roth, S. M., Walsh, S., Liu, D., Metter, E. J., Ferrucci, L., Hurley, B. F. The ACTN3 R577X nonsense allele is underrepresented in elite-level strength athletes. Europ. J. Hum.
Genet. 16: 391-394, 2008.
22) Clarkson, Priscilla M., Eric P. Hoffman, Edward Zambraski, Heather Gordish-Dressman, Amy
Kearns, Monica Hubal, Brennan Harmon, and Joseph M. Devaney. "ACTN3 and MLCK
Genotype Associations with Exertional Muscle Damage." Journal of Applied
Physiology 99.2 (2005): 564-69. Web. 25 Oct. 2011.
<http://jap.physiology.org/content/99/2/564.full>.
23) Davidson College. "RFLP Method - Restriction Fragment Length Polymorphism." RFLP
Method. Web. 22 Nov. 2011.
<http://www.bio.davidson.edu/courses/genomics/method/RFLP.html>.
24) Mills, Michelle, Nan Yang, Ron Weinberger, Douglas L. Vander Woude, Alan H. Beggs, Simon
Easteal, and Kathryn North. "Differential Expression of the Actin-binding Proteins, αactinin-2 and -3, in Different Species: Implications for the Evolution of Functional
Redundancy." Oxford Journals 10.13 (2001): 1335-346. Web. 25 Oct. 2011. < http://hmg.oxfordjournals.org/content/10/13/1335.full#sec-15>.
25) "Yannis Pitsiladis." Yannis Pitsiladis. Idefics Study, 2006. Web. 26 Oct. 2011.
<http://www.idefics.eu/Idefics/webcontent?cmd=innerDoc&path=3314&start=true>.
26) Epstein, David. "WHO HAS THE SPEED GENE, AND WHO DOESN'T? HOW MUCH OF -
05.17.10 - SI Vault." Breaking News, Real-time Scores and Daily Analysis from Sports

Illustrated – SI.com. Web. 26 Oct. 2011.
<http://sportsillustrated.cnn.com/vault/article/magazine/MAG1169440/4/index.htm
27) Davids, Keith, and Joseph Baker. "Genes, Environment and Sport Performance." Sports
Medicine 37.11 (2007): 961-80. Print.
28) North, K. N., Yang, N., Wattanasirichaigoon, D., Mills, M., Easteal, S., Beggs, A. H. A common nonsense mutation results in alpha-actinin-3 deficiency in the general population. Nature Genet. 21: 353-354, 1999.
29) Mayo Clinic Staff. "Exercise: 7 Benefits of Regular Physical Activity." Exercise: 7 Benefits of
Regular Physical Activity - MayoClinic.com. 23 July 2011. Web. 19 Nov. 2011.
<http://www.mayoclinic.com/health/exercise/HQ01676>.