Inheritance: How Our Genes Change Our Lives--and Our Lives Change Our Genes

by Moalem MD PhD, Sharon

  11L. Yan et al. (2012). Association of the maternal MTHFR C677T polymorphism with susceptibility to neural tube defects in offsprings: Evidence from 25 case-control studies. PLOS One, 7: e41689.

  12A. Keller et al. (2012). New insights into the Tyrolean Iceman’s origin and phenotype as inferred by whole-genome sequencing. Nature Communications, 3: 698.

  13I can’t guarantee that signing up for the service won’t result in a visit by LDS church missionaries: www.familysearch.org.

  Chapter 7: Picking Sides

  1If you’re not a surfing fan, you might remember Occhilupo from his stint on Dancing with the Stars. To learn more of the incredible story that came before he quickstepped his way into elimination on that popular TV show, read: M. Occhilupo and T. Baker (2008). Occy: The Rise and Fall and Rise of Mark Occhilupo. Melbourne: Random House Australia.

  2P. Hilts (1989, Aug. 29). A sinister bias: New studies cite perils for lefties. The New York Times.

  3L. Fritschi et al. (2007). Left-handedness and risk of breast cancer. British Journal of Cancer, 5: 686–687.

  4If you’d like to see the Walt Disney short Hawaiian Holiday, go to the following link: www.youtube.com/watch?v=SdIaEQCUVbk.

  5E. Domellöf et al. (2011). Handedness in preterm born children: A systematic review and a meta-analysis. Neuropsychologia, 49: 2299–2310.

  6If you’re interested in learning more about this topic than you can read more: O. Basso (2007). Right or wrong? On the difficult relationship between epidemiologists and handedness. Epidemiology,18: 191–193.

  7A. Rodriguez et al. (2010). Mixed-handedness is linked to mental health problems in children and adolescents. Pediatrics, 125: e340–e348.

  8G. Lynch et al. (2001). Tom Blake: The Uncommon Journey of a Pioneer Waterman. Irvine: Croul Family Foundation.

  9M. Ramsay (2010). Genetic and epigenetic insights into fetal alcohol spectrum disorders. Genome Medicine, 2: 27; K. R. Warren and T. K. Li. (2005). Genetic polymorphisms: Impact on the risk of fetal alcohol spectrum disorders. Birth Defects Research Part A: Clinical and Molecular Teratology, 73: 195–203.

  10E. Domellöf et al. (2009). Atypical functional lateralization in children with fetal alcohol syndrome. Developmental Psychobiology, 51: 696–705.

  11Naranjo’s story is nothing short of amazing. Be sure to check out the videos of him at work on YouTube, and don’t miss: B. Edelman (2002, July 2). Michael Naranjo: The artist who sees with his hands. Veterans Advantage. http://www.veteransadvantage.com/cms/content/michael-naranjo

  12S. Moalem et al. (2013). Broadening the ciliopathy spectrum: Motile cilia dyskinesia, and nephronophthisis associated with a previously unreported homozygous mutation in the INVS/NPHP2 gene. American Journal of Medical Genetics Part A, 161:1792–1796.

  13Did the meteorite simply pick up an extra smattering of aminos when it hit the lake? The scientists accounted for that: D. P. Glavin et al. (2012). Unusual nonterrestrial l-proteinogenic amino acid excesses in the Tagish Lake meteorite. Meteoritics & Planetary Science, 47: 1347–1364.

  14S. N. Han et al. (2004). Vitamin E and gene expression in immune cells. Annals of the New York Academy of Sciences,1031: 96–101.

  15G. J. Handleman et al. (1985). Oral alpha-tocopherol supplements decrease plasma gamma-tocopherol levels in humans. The Journal of Nutrition, 115: 807–813.

  16J. M. Major et al. (2012). Genome-wide association study identifies three common variants associated with serologic response to vitamin E supplementation in men. The Journal of Nutrition, 142: 866–871.

  Chapter 8: We’re All X-Men

  1For more information, visit the National Geographic Project: www. nationalgeographic.com

  2M. Hanaoka et al. (2012). Genetic variants in EPAS1 contribute to adaptation to high-altitude hypoxia in Sherpas. PLOS One, 7: e50566.

  3One of the signs that pilots and aircrew members watch out for is an unexpected fit of giggling, which can be a sign that less oxygen is available due to an aircraft’s fuselage becoming depressurized.

  4P. H. Hackett (2010). Caffeine at high altitude: Java at base camp. High Altitude Medicine & Biology, 11: 13–17.

  5Coca-Cola’s slogan back in the mid-1940s.

  6A. de La Chapelle et al. (1993). Truncated erythropoietin receptor causes dominantly inherited benign human erythrocytosis. Proceedings of the National Academy of Sciences, 90: 4495–4499.

  7Apa Sherpa has made yearly returns to Nepal several times to raise awareness of climate change and the desperate need for better education in the Sherpa community, since moving to the United States with his wife and children in 2006. To read more about Apa Sherpa see the following article: M. LaPlante (2008, June 2). Everest record-holder proudly calls Utah home. The Salt Lake Tribune.

  8D. J. Gaskin et al. (2012). The economic costs of pain in the United States. The Journal of Pain, 13: 715–724.

  9B. Huppert (2011, Feb. 9). Minn. girl who feels no pain, Gabby Gingras, is happy to “feel normal.” KARE11; K. Oppenheim (2006, Feb. 3). Life full of danger for little girl who can’t feel pain. CNN.com.

  10J. J. Cox et al. (2006). An SCN9A channelopathy causes congenital inability to experience pain. Nature, 444: 894-–898.

  Chapter 9: Hacking Your Genome

  1If you’d like more information regarding statistics related to the prevalence of many different types of cancer, the American Cancer Society website is a good place to start: www.cancer.org.

  2C. Brown (2009, Apr.). The king herself. National Geographic, 215(4).

  3It is still unclear what exact role diet played in the development of cancer in certain species of dinosaurs, since not all species seemed to be equally affected. If you’d like to read more about this fascinating work, see: B. M. Rothschild et al. (2003). Epidemiologic study of tumors in dinosaurs. Naturwissenschaften, 90: 495–500, and J. Whitfield (2003, Oct. 21). Bone scans reveal tumors only in duck-billed species. Nature News.

  4World Health Organization.

  5For more information about the rates and causes of lung cancer, see the Centers for Disease Control and Prevention’s website, www.cdc.gov.

  6A. Marx. (1994–1995, Winter). The ultimate cigar aficionado. Cigar Aficionado.

  7This in spite of the fact that many of these publications were well funded by cigarette advertising.

  8R. Norr. (1952, December). Cancer by the carton. The Reader’s Digest.

  9If you’re interested in additional historical figures related to smoking, see the website www.lung.org.

  10See It Now, (1955, June 7). Transcribed from a tape recording made for Hill and Knowlton, Inc., during the telecast on CBS-TV.

  11U.S. Department of Agriculture. (2007). Tobacco Situation and Outlook Report Yearbook; Centers for Disease Control and Prevention. National Center for Health Statistics. National Health Interview Survey 1965–2009.

  12The entire transcript of “Cigarettes and Lung Cancer” from the June 7, 1955, edition of See It Now can be found online at the Legacy Tobacco Documents Library’s website, www.legacy.library.ucsf.edu/tid/ppq36b00.

  13There’s a lot of speculation about what saber-toothed cats (they weren’t actually tigers) hunted, but researchers have noted that they were in the right place at the right time to chow down on some of our earliest ancestors: L. de Bonis et al. (2010). New saber-toothed cats in the Late Miocene of Toros Menalla (Chad). Comptes Rendus Palevol., 9: 221–227.

  14B. Ramazzini (2001). De Morbis Artificum Diatriba. American Journal of Public Health, 91: 1380–1382.

  15T. Lewin (2001, February 10). Commission sues railroad to end genetic testing in work injury cases. The New York Times.

  16P. A. Schulte and G. Lomax (2003). Assessment of the scientific basis for genetic testing of railroad workers with carpal tunnel syndrome. Journal of Occupational and Environmental Medicine, 45: 592–600.

  17These were generally families with uncommon conditions, and the rarity of the disorders they harbored might have might it easier for researchers to identify them, but the ease with w
hich the researchers were able to identify patients is nonetheless disconcerting: M. Gymrek et al. (2013). Identifying personal genomes by surname inference. Science, 339: 321–324.

  18J. Smith (2013, Apr. 16). How social media can help (or hurt) you in your job search. Forbes.com.

  19In the U.S., employers and health insurance providers are limited in the genetic information they can seek.

  20In 2012, however, the Presidential Commission for the Study of Bioethical Issues issued a report calling for such tests to be made illegal, citing widespread privacy concerns: S. Begley (2012, Oct. 11). Citing privacy concerns, U.S. panel urges end to secret DNA testing. Reuters.

  21A. Jolie (2013, May 14). My medical choice. The New York Times.

  22D. Grady et al. (2013, May 14). Jolie’s disclosure of preventive mastectomy highlights dilemma. The New York Times.

  Chapter 10: Mail-Order Child

  1Wrecksite is the world’s largest online database of shipwrecks, with information on the final resting places of more than 140,000 ships. It’s also a treasure trove of information about what many of those ships were doing when they met their fateful ends: http://www.wrecksite.eu.

  2See: I. Donald (1974). Apologia: How and why medical sonar developed. Annals of the Royal College of Surgeons of England, 54: 132–140.

  3This story and many more about German submarines can be found at www.uboat.net.

  4R. Brooks. (2013, Mar. 4). China’s biggest problem? Too many men. CNN.com.

  5Y. Chen et al. (2013). Prenatal sex selection and missing girls in China: Evidence from the diffusion of diagnostic ultrasound. The Journal of Human Resources, 48: 36–70.

  6At one point in American history—and not so long ago—clothing “experts” advised parents to dress boys in pink and girls in blue. But by the 1950s and ’60s, the gender paradigm had flipped. It might have flipped back or changed completely just as in-fashion colors do for adults had it not been for the advent of ultrasounds and sonograms: J. Paoletti (2012). Pink and Blue: Telling the Boys from the Girls in America. Indiana University Press.

  7This case presents a composite of previously published case reports and other similar patient encounters, with names, descriptions, and scenarios altered.

  8The Mayo Clinic’s Disease Index has a detailed series of pages dedicated to hypospadias and thousands of other conditions: http://www.mayoclinic.com/health/DiseasesIndex.

  9It’s possible that this is one of the most frequent autosomal recessive genetic disorders in human beings. P. W. Speiser et al. (1985). High frequency of nonclassical steroid 21-hydroxylase deficiency. American Journal of Human Genetics, 37: 650–667.

  10Like a clock, one arm is short (which we designate as “p”) and the other is usually longer (we designate it as “q”). Each chromosome has a unique banding pattern, which creates its barcode-like appearance under the microscope. It’s these unique banding patterns that cytogeneticists use to identify and evaluate the integrity and quality of our chromosomes.

  11Unlike a karyotype, one of the important limitations of an aCGH is that it doesn’t let you know if there’s been a balanced movement or inversion of genetic material from one area in the genome to another. This is important because if we use the same example of encyclopedic volumes such a change can result in an entry being out of order, which for our genomes can be problematic. An aCGH cannot tell you if that has occurred.

  12Among other superstitions about hijras, many Indians believe that they must be present or nearby on wedding days to bring about good luck: N. Harvey (2008, May 13). India’s transgendered—the Hijras. New Statesman.

  13Moreschi’s complete recordings, which are scratchy and sometimes uneven but nonetheless spellbinding, are available on an 18-track compact disc, The Last Castrato. (1993). Opal.

  14K. J. Min et al. (2012). The lifespan of Korean eunuchs. Current Biology, 22: R792–R793.

  15Often wrongly attributed to Ralph Waldo Emerson, the slogan appears to have first appeared in a book by an anonymous securities trader whose identity was only years later publicly revealed by the New York Times. See H. Haskins (1940). Meditations in Wall Street. New York: William Morrow.

  Chapter 11: Putting It All Together

  1More than the entire population of the state of Texas: National Organization for Rare Disorders.

  2Fat gets a bad name. For most people, it’s vital, and as this study found, the relationship between fat intake and reports of depression may be more complicated than we initially anticipated and may depend on the particular type of fat: A. Sánchez-Villegas et al. (2011). Dietary fat intake and the risk of depression: The SUN Project. PLOS One, 26: e16268.

  3Heart disease is sometimes called a “hidden” epidemic: D. L. Hoyert and J. Q. Xu. (2012). Deaths: Preliminary data for 2011. National Vital Statistics Reports, 61: 1–52.

  4S. C. Nagamani et al. (2012). Nitric-oxide supplementation for treatment of long-term complications in argininosuccinic aciduria. American Journal of Human Genetics, 90: 836–846; C. Ficicioglu et al. (2009). Argininosuccinate lyase deficiency: Longterm outcome of 13 patients detected by newborn screening. Molecular Genetics and Metabolism, 98: 273–277.

  5A. Williams (2013, Apr. 3). The Ecuadorian dwarf community “immune to cancer and diabetes” who could hold cure to diseases. The Daily Mail.

  6Gorlin syndrome isn’t the only reason for toes webbed in this way. If you have syndactyly, it doesn’t automatically mean you’re likely to get skin cancer.

  7N. Boutet et al. (2003). Spectrum of PTCH1 mutations in French patients with Gorlin syndrome. The Journal of Investigative Dermatology, 121: 478–481.

  8A. Case and C. Paxson (2006). Stature and Status: Height, Ability, and Labor Market Outcomes. National Bureau of Economic Research Working Paper No. 12466.

  9The French have long fought a losing battle against the idea that Napoléon was short and that his height played a factor in his empiric ambitions: M. Dunan (1963). La taille de Napoléon. La Revue de l’Institut Napoléon, 89: 178–179.

  10V. Ayyar (2011). History of growth hormone therapy. Indian Journal of Endocrinology and Metabolism, 15: S162–S165.

  11A. Rosenbloom (2011). Pediatric endo-cosmetology and the evolution of growth diagnosis and treatment. The Journal of Pediatrics,158: 187–193.

  Acknowledgments

  I am grateful and indebted to all the patients and their families who have let me retell the stories of their medical journeys throughout the pages of Inheritance. I’m also extremely grateful to all the teachers and mentors I’ve had over the years, in medicine and beyond. I’m especially thankful to David Chitayat, MD, whose continual and inspirational support and enthusiasm for this project from its very early infancy was so crucial to its final success; over the years he has also generously shared with me his contagious passion for dysmorphology, genetics, and medicine. My agent Richard Abate of 3 Arts believed in this project from the start and was instrumental in conveying the importance of capturing, “how a geneticist thinks.” The manuscript was immensely improved by the suggestions and direction of many readers. I must especially acknowledge my wonderful executive editor Ben Greenberg at Grand Central Publishing, whose intellectual probing and persistence helped bring clarity to complex genetic processes and ideas. Ben was also one of the earliest champions of Inheritance and was critical in ensuring the book received the audience he believed it deserves. I also would like to thank Drummond Moir, my UK editor at Scepter for some last minute editorial pinch-hitting and helpful suggestions. To Yasmin Mathew, for her meticulous work as the production editor. And to Melissa Khan of 3 Arts, and Pippa White at Grand Central for always staying one step ahead administratively, and making it a surprising pleasure to meet deadlines. As well, to my publicists Matthew Ballast at Grand Central, as well as Catherine Whiteside, who both did such a wonderful job in raising essential awareness about the book. My research assistant Richard Verver continues to astound me with his unwaveringly sharp eye, and his relentless pursuit of original sources regardle
ss of any language barriers. To Alaina deHavillard of Wailele Estates Kona Coffee whose masterful brew inspired page after page of this book. And to Wally whose gracious hospitality and welcoming home created the perfect ambiance to finish this project. As well, a special thank you to Jordan Peterson who spent an immense amount of time and energy on suggestions regarding the refinement of the manuscript. And of course to Matthew LaPlante who elevated this whole project with his immense journalistic talent and his refreshing sense of humor. Last but never least to my family and friends, for your endless love, support, and constant enthusiasm for every new project and undertaking.

  About the Author

  Sharon Moalem MD, PhD, is an award-winning scientist, physician, and New York Times bestselling author. His research and writing blends medicine, genetics, history, and biology to explain how the human body functions in new and fascinating ways. He is also the author of the New York Times bestseller Survival of the Sickest and How Sex Works. His books have been translated into more than 30 languages.

  Dr. Moalem served as an associate editor for the Journal of Alzheimer’s Disease. His scientific work has led to his discovery of Siderocillin, a novel antibiotic drug directed against multiresistant or ‘superbug’ microorganisms. He has also been awarded twenty patents for inventions related to biotechnology and human health, and has cofounded two biotechnology companies. Dr. Moalem and his research have been featured in the New York Times, New Scientist, Time magazine, and on The Daily Show with Jon Stewart, CNN, and The Today Show.

  Thank you for buying this ebook, published by Hachette Digital.