Remember what that orphanage worker told them? “You are her destiny,” she said. Not her genes. Not her brittle bones. The woman and man who decided they needed to be her parents and who gave her the gift of a completely new birthright. A new chance to survive, despite her genetic inheritance, and the opportunity to thrive.
As we’re discovering, our genetic strength isn’t just a matter of receiving the genes handed down to us from previous generations. It’s derived from the opportunity to transform what we get and what we give.
And in doing so completely change the course of our lives.
Notes
Chapter 1: How Geneticists Think
1Some names in this book have been changed and some identities, descriptions and scenarios have been altered or combined to protect the confidentiality of patients, friends, acquaintances, and colleagues, or to give clarity to an existing idea or diagnosis.
2Although the price has come down significantly for both exome and whole genome sequencing, the time and cost associated with the interpretation of the data still needs to be considered.
3There are some fundamental psychological principles at play here. For further reference, read J. Nevid (2009). Psychology Concepts and Applications. Boston: Houghton Mifflin.
4M. Rosenfield (1979, Jan. 15). Model expert offers “something special.” The Pittsburgh Press.
5P. Pasols (2012). Louis Vuitton: The Birth of Modern Luxury. New York: Abrams.
6The National Center for Biotechnology Information is a comprehensive and reliable public resource for information on all kinds of diseases, including Fanconi anemia: www.ncbi.nlm.nih.gov.
7Rearrangements of the PAX3 gene are also thought to be involved in some forms of rare cancers called alveolar rhabdomyosarcoma. S. Medic and M. Ziman (2010). PAX3 expression in normal skin melanocytes and melanocytic lesions (naevi and melanomas). PLOS One, 5: e9977.
8About one child in every 700 live births has Down syndrome.
9Although not routinely employed today, analysis of fetal meconium can be used to test for gestational alcohol exposure by the presence of chemicals called fatty acid ethyl esters or FAEEs.
10If having a fat thumb is something that should be kept hidden, what does that say to those of us who have even more severe and debilitating physical anomalies? This, to me, is an extremely sad statement about the lengths that marketers have gone to establish the idea of perfect people—and especially perfect women. See I. Lapowsky (2010, Feb. 8). Megan Fox uses a thumb double for her sexy bubble bath commercial. New York Daily News.
11K. Bosse et al. (2000). Localization of a gene for syndactyly type 1 to chromosome 2q34-q36. American Journal of Human Genetics, 67: 492–497.
12Marriage between relatives can increase the likelihood of genetic disorders anywhere from double the risk to higher, depending upon the ethnicity of the family.
13Dysmorphology is a subspecialty of medicine that uses our anatomical features to understand our genetic and environmental history. If the terminology used by dysmorphologists excites you, I suggest reading Special Issue: Elements of Morphology: Standard Terminology. (2009). American Journal of Medical Genetics Part A, 149: 1–127. If you’d like to learn more about this fascinating field, start with The Journal Clinical Dysmorphology, a peer-reviewed collection of articles on cases and research related to this field.
Chapter 2: When Genes Misbehave
1S. Manzoor (2012, Nov. 2). Come inside: The world’s biggest sperm bank. The Guardian.
2C. Hsu (2012, Sept. 25). Denmark tightens sperm donation law after “Donor 7042” passes rare genetic disease to 5 babies. Medical Daily.
3R. Henig (2000). The Monk in the Garden: The Lost and Found Genius of Gregor Mendel, the Father of Genetics. New York: Houghton Mifflin.
4In Mendel’s original publication he used the German word vererbung, which we would translate in English as “inheritance.” The use of the term predates Mendel’s paper.
5D. Lowe (2011, Jan. 24). These identical twins both have the same genetic defect. It affects Neil on the inside and Adam on the outside. U.K.: The Sun.
6M. Marchione (2007, Apr. 5). Disease underlies Hatfield-McCoy feud. The Associated Press.
7If you’d like to learn more about von Hippel-Lindau disease and support organizations, please see the following NORD website: www.rarediseases.org/rare-disease-information/rare-diseases/byID/181/viewFullReport.
8L. Davies (2008, Sept. 18). Unknown Mozart score discovered in French library. The Guardian.
9M. Doucleff (2012, Feb. 11). Anatomy of a tear-jerker: Why does Adele’s “Someone Like You” make everyone cry? Science has found the formula. The Wall Street Journal.
10You can listen to Leisinger play Mozart’s piano at www.themozartfestival.org.
11G. Yaxley et al. (2012). Diamonds in Antarctica? Discovery of Antarctic Kimberlites Extends Vast Gondwanan Cretaceous Kimberlite Province. Research School of Earth Sciences, Australian National University.
12E. Goldschein (2011, Dec. 19). The incredible story of how De Beers created and lost the most powerful monopoly ever. Business Insider.
13E. J. Epstein (1982, Feb. 1). Have you ever tried to sell a diamond? The Atlantic.
14H. Ford and S. Crowther (1922). My Life and Work. Garden City, NY: Garden City Publishing.
15D. Magee (2007). How Toyota Became #1: Leadership Lessons from the World’s Greatest Car Company. New York: Penguin Group.
16A. Johnson (2011, Apr. 16). One giant step for better heart research? The Wall Street Journal.
17There are many papers published on this topic. Here is one I particularly enjoy reading: H. Katsume et al. (1992). Disuse atrophy of the left ventricle in chronically bedridden elderly people. Japanese Circulation Journal, 53: 201–206.
18J. M. Bostrack and W. Millington (1962). On the determination of leaf form in an aquatic heterophyllous species of Ranunculus. Bulletin of the Torrey Botanical Club, 89: 1–20.
Chapter 3: Changing Our Genes
1This paper is cited by nearly a hundred others and stands out as a landmark: M. Kamakura (2011). Royalactin induces queen differentiation in honeybees. Nature, 473: 478. If you find bees as fascinating as I do, you might like to read this paper as well: A. Chittka and L. Chittka (2010). Epigenetics of royalty. PLOS Biology, 8: e1000532.
2F. Lyko et al. (2010). The honeybee epigenomes: Differential methylation of brain DNA in queens and workers. PLOS Biology, 8: e1000506.
3R. Kucharski et al. (2008). Nutritional control of reproductive status in honeybees via DNA methylation. Science, 319: 1827–1830.
4B. Herb et al. (2012). Reversible switching between epigenetic states in honeybee behavioral subcastes. Nature Neuroscience, 15: 1371–1373.
5Humans have two different versions, DNMT3A and DNMT3B, which have shared homology and similarity in the catalytic domain to the Dnmt3 gene found in Apis mellifera, the honeybee. If you’d like to read more about this, see the following paper: Y. Wang et al. (2006). Functional CpG methylation system in a social insect. Science, 27: 645–647.
6M. Parasramka et al. (2012). MicroRNA profiling of carcinogen-induced rat colon tumors and the influence of dietary spinach. Molecular Nutrition & Food Research, 56: 1259–1269.
7A. Moleres et al. (2013). Differential DNA methylation patterns between high and low responders to a weight loss intervention in overweight or obese adolescents: The EVASYON study. FASEB Journal, 27: 2504–2512.
8T. Franklin et al. (2010). Epigenetic transmission of the impact of early stress across generations. Biological Psychiatry, 68: 408–415.
9R. Yehuda et al. (2009). Gene expression patterns associated with posttraumatic stress disorder following exposure to the World Trade Center attacks. Biological Psychiatry, 66: 708–711; R. Yehuda et al. (2005). Transgenerational effects of posttraumatic stress disorder in babies of mothers exposed to the World Trade Center attacks during pregnancy. Journal of Clinical Endocrinology & Metabolism, 90: 4115–4118.
10S. Sookoian et al. (2013).
Fetal metabolic programming and epigenetic modifications: A systems biology approach. Pediatric Research, 73: 531–542.
Chapter 4: Use It Or Lose It
1E. Quijano (2013, Mar. 4). “Kid President”: A boy easily broken teaching how to be strong. CBSNews.com.
2Thankfully, these sorts of stories are quite rare. Nonetheless, this is an incredibly tragic tale. H. Weathers (2011, Aug. 19). They branded us abusers, stole our children and killed our marriage: Parents of boy with brittle bones attack social workers who claimed they beat him. The Daily Mail.
3U.S. Department of Health & Human Services (2011). Child Maltreatment.
4FOP was detailed in medical literature as far back as 250 years ago, but the disease’s cause was a medical mystery until fairly recently. If you’d like to read more on FOP see the following paper: F. Kaplan et al. (2008). Fibrodysplasia ossificans progressiva. Best Practice & Research: Clinical Rheumatology. 22: 191–205.
5Ali’s family has raised an “army” for their daughter and others who suffer from FOP: N. Golgowski (2012, June 1). The girl who is turning into stone: Five year old with rare condition faces race against time for cure. The Daily Mail.
6Today, keeping an eye on the big toes of people suspected of FOP is part of the standard dysmorphology exam: M. Kartal-Kaess et al. (2010). Fibrodysplasia ossificans progressiva (FOP): Watch the great toes. European Journal of Pediatrics, 169: 1417–1421.
7A. Stirland (1993). Asymmetry and activity related change in the male humerus. International Journal of Osteoarcheology, 3: 105–113.
8The Mary Rose remained on the seabed until it was raised in 1982. Ever since then, scientists have been racing to uncover the identities and life stories of the sailors aboard: A. Hough (2012, Nov. 18). Mary Rose: Scientists identify shipwreck’s elite archers by RSI. The Telegraph.
9If you happen to be interested in the heritability of bunions, please see M. T. Hannan et al. (2013). Hallux valgus and lesser toe deformities are highly heritable in adult men and women: The Framingham foot study. Arthritis Care Research (Hoboken). [Epub ahead of print.]
10In any other context, a loaded backpack might be considered a torture device. See D. H. Chow et al. (2010). Short-term effects of backpack load placement on spine deformation and repositioning error in schoolchildren. Ergonomics, 53: 56–64.
11A. A. Kane et al. (1996). Observations on a recent increase in plagiocephaly without synostosis. Pediatrics, 97: 877–885; W. S. Biggs (2004). The “epidemic” of deformational plagiocephaly and the American Academy of Pediatrics’ response. JPO: Journal of Prosthetics and Orthotics, 16: S5–S8.
12Before you invest in a cranial remodeling helmet please consider J. F. Wilbrand et al. (2013). A prospective randomized trial on preventative methods for positional head deformity: Physiotherapy versus a positioning pillow. The Journal of Pediatrics, 162: 1216–1221.
13It’s a fantastically fascinating fish. For more information please see J. G. Lundberg and B. Chernoff (1992). A Miocene fossil of the Amazonian fish Arapaima (Teleostei Arapaimidae) from the Magdalena River region of Colombia—Biogeographic and evolutionary implications. Biotropica, 24: 2–14.
14M. A. Meyers et al. (2012). Battle in the Amazon: Arapaima versus piranha. Advanced Engineering Materials. 14: 279–288.
15A very small genetic change that led to a lethal type of OI was just one of the first of many high-profile revelations of the power of a change in a single nucleotide. See D. H. Cohn et al. (1986). Lethal osteogenesis imperfecta resulting from a single nucleotide change in one human pro alpha 1(I) collagen allele. Proceedings of the National Academy of Science, 83: 6045–6047.
16D. R. Taaffe et al. (1995). Differential effects of swimming versus weight-bearing activity on bone mineral status of eumenorrheic athletes. Journal of Bone and Mineral Research, 10: 586–593.
17The photos and videos that accompanied this story about the space capsule landing show the three spacemen struggling with their sudden reimmersion in Earth’s gravity. See P. Leonard (2012, July 2). “It’s a bullseye”: Russian Soyuz capsule lands back on Earth after 193-day space mission. Associated Press.
18A. Leblanc et al. (2013). Bisphosphonates as a supplement to exercise to protect bone during long-duration spaceflight. Osteoporosis International, 24: 2105–2114.
Chapter 5: Feed Your Genes
1F. Rohrer (2007, Aug. 7). “China drinks its milk.” BBC News Magazine.
2Which makes sense, given the fact that many people don’t know how to cook much at all, let alone cook food that is tasty and nutritious. See this paper for more information: P. J. Curtis et al. (2012). Effects on nutrient intake of a family-based intervention to promote increased consumption of low-fat starchy foods through education, cooking skills and personalized goal. British Journal of Nutrition, 107: 1833–1844.
3D. Martin (2011, Aug. 18). From omnivore to vegan: The dietary education of Bill Clinton. CNN.com.
4S. Bown (2003). Scurvy: How a Surgeon, a Mariner and a Gentleman Solved the Greatest Medical Mystery of the Age of Sail. West Sussex: Summersdale Publishing Ltd.
5L. E. Cahill and A. El-Sohemy (2009). Vitamin C transporter gene polymorphisms, dietary vitamin C and serum ascorbic acid. Journal of Nutrigenetics and Nutrigenomics, 2: 292–301.
6H. C. Erichsen et al. (2006). Genetic variation in the sodium-dependent vitamin C transporters, SLC23A1, and SLC23A2 and risk for preterm delivery. American Journal of Epidemiology, 163: 245–254.
7If you’d like to read more, here’s a paper that explores some of these ideas: E. L. Stuart et al. (2004). Reduced collagen and ascorbic acid concentrations and increased proteolytic susceptibility with prelabor fetal membrane rupture in women. Biology of Reproduction. 72: 230–235.
8Jeff the Chef, whom we met in the introduction, found himself in this position when he followed his doctor’s nutritional advice.
9If you’d like to read more about the pharmacogenetics of caffeine intake, see: Palatini et al. (2009). CYP1A2 genotype modifies the association between coffee intake and the risk of hypertension. Journal of Hypertension, 27:1594–601 and M. C. Cornelis et al. (2006). Coffee, CYP1A2 genotype, and risk of myocardial infarction. The Journal of the American Medical Association, 295:1135–1141.
10I. Sekirov et al. (2010). Gut microbiota in health and disease. Physiological Reviews, 90: 859–904.
11Often there needs to be a waiting period of a few weeks for room to develop in the growing body cavity. A specialized temporary packing called a silo is constructed around the intestines to protect the baby’s intestines during the wait. Although the silo can be very visually disconcerting to the parents and family of a child with gastroschisis, this period of time is necessary for enough room to develop to accept the intestines, so that they can be safely packed back into the body and the wall surgically closed and corrected.
12N. Fei and L. Zhao (2013). An opportunistic pathogen isolated from the gut of an obese human causes obesity in germfree mice. The ISME Journal, 7: 880–884.
13If you’re interested to read more about this topic, see the following paper: R. A. Koeth et al. (2013). Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis. Nature Medicine, 19: 576–585.
14S. A. Centerwall and W. R. Centerwall (2000). The discovery of phenylketonuria: The story of a young couple, two retarded children, and a scientist. Pediatrics, 105: 89–103.
15P. Buck (1950). The Child Who Never Grew. New York: John Day.
Chapter 6: Genetic Dosing
1If you’d like to read more about cases like Meghan’s, here’s a good place to start: L. E. Kelly et al. (2012). More codeine fatalities after tonsillectomy in North American children. Pediatrics, 129: e1343–1347.
2What happened in those intervening years? A lot of slow movement toward a lifesaving conclusion. Many times, unfortunately, that’s how medical science works. See B. M. Kuehn (2013). FDA: No codeine after tonsillectomy for children. Journal of the American Medical Association, 309: 1100.
4Rose, who died in 1993, is a hero to many doctors and researchers—and rightfully so: B. Miall (1993, Nov. 16). Obituary: Professor Geoffrey Rose. The Independent.
5Much as we know that the effects of codeine vary widely depending on a person’s genetic inheritance, so, too, have we learned that the effects of just about every medical intervention can be very different from person to person, sometimes for the better and sometimes for the worse: G. Rose (1985). Sick individuals and sick populations. International Journal of Epidemiology, 14: 32–38.
6See A. M. Minihane et al. (2000). APOE polymorphism and fish oil supplementation in subjects with an atherogenic lipoprotein phenotype. Arteriosclerosis, Thrombosis, and Vascular Biology, 20: 1990–1997; A. Minihane (2010). Fatty acid-genotype interactions and cardiovascular risk. Prostaglandins, Leukotrienes and Essential Fatty Acids, 82: 259–264.
7M. Park (2011, April 13). Half of Americans use supplements. CNN.com.
8H. Bastion (2008). Lucy Wills (1888–1964): The life and research of an adventurous independent woman. The Journal of the Royal College of Physicians of Edinburgh, 38: 89–91.
9M. Hall (2012). Mish-Mash of Marmite: A–Z of Tar-in-a-Jar. London: BeWrite Books.
10If you’d like to read more about these findings, see: P. Surén et al. (2013). Association between maternal use of folic acid supplements and risk of autism spectrum disorders in children. The Journal of the American Medical Association, 309: 570–577.
Inheritance: How Our Genes Change Our Lives--and Our Lives Change Our Genes Page 23