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Genetic testing

Authors
Benjamin A Raby, MD, MPH
Wendy Kohlmann, MS, CGC
Vickie Venne, MS, CGC
Section Editor
Anne Slavotinek, MBBS, PhD
Deputy Editor
Jennifer S Tirnauer, MD

INTRODUCTION

Genetic testing is becoming more important in allowing tailored interventions in "personalized" or "precision" medicine. Genetic conditions are responsible for over 35 percent of pediatric medical conditions. In adults, disease risk for common conditions is more likely to be related to a combination of multifactorial genetic and non-genetic factors.

Targeting genetic testing appropriately and understanding the limitations and challenges of available testing approaches are crucial to the successful use of genetics in improving health and quality of life. As primary care clinicians are more frequently asked about genetic testing, they can collaborate with colleagues to assure that genetic advances are applied usefully to patient care.

This topic reviews principles of genetic testing and provides general information about the use of genetic testing to evaluate patients for inherited conditions.

Additional discussions are provided on the following topics:

Genetic counseling – (See "Genetic counseling: Family history interpretation and risk assessment".)

                    

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Literature review current through: Nov 2016. | This topic last updated: Wed Oct 19 00:00:00 GMT+00:00 2016.
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References
Top
  1. https://www.genetests.org/tests/tests.php?type=P.
  2. Gregg AR, Skotko BG, Benkendorf JL, et al. Noninvasive prenatal screening for fetal aneuploidy, 2016 update: a position statement of the American College of Medical Genetics and Genomics. Genet Med 2016; 18:1056.
  3. http://www.acog.org/-/media/Committee-Opinions/Committee-on-Genetics/co640.pdf?dmc=1&ts=20150714T0302215403.
  4. Ford D, Easton DF, Stratton M, et al. Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium. Am J Hum Genet 1998; 62:676.
  5. Struewing JP, Hartge P, Wacholder S, et al. The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. N Engl J Med 1997; 336:1401.
  6. Domchek SM, Friebel TM, Singer CF, et al. Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. JAMA 2010; 304:967.
  7. Burke W, Press N, Pinsky L. BRCA1 and BRCA2: a small part of the puzzle. J Natl Cancer Inst 1999; 91:904.
  8. Easton DF, Ford D, Bishop DT. Breast and ovarian cancer incidence in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Am J Hum Genet 1995; 56:265.
  9. Thorlacius S, Struewing JP, Hartge P, et al. Population-based study of risk of breast cancer in carriers of BRCA2 mutation. Lancet 1998; 352:1337.
  10. Peto J, Collins N, Barfoot R, et al. Prevalence of BRCA1 and BRCA2 gene mutations in patients with early-onset breast cancer. J Natl Cancer Inst 1999; 91:943.
  11. Fodor FH, Weston A, Bleiweiss IJ, et al. Frequency and carrier risk associated with common BRCA1 and BRCA2 mutations in Ashkenazi Jewish breast cancer patients. Am J Hum Genet 1998; 63:45.
  12. Welch HG, Burke W. Uncertainties in genetic testing for chronic disease. JAMA 1998; 280:1525.
  13. Galiatsatos P, Foulkes WD. Familial adenomatous polyposis. Am J Gastroenterol 2006; 101:385.
  14. Breitner JC, Wyse BW, Anthony JC, et al. APOE-epsilon4 count predicts age when prevalence of AD increases, then declines: the Cache County Study. Neurology 1999; 53:321.
  15. Cogswell ME, McDonnell SM, Khoury MJ, et al. Iron overload, public health, and genetics: evaluating the evidence for hemochromatosis screening. Ann Intern Med 1998; 129:971.
  16. Hampel H, Frankel WL, Martin E, et al. Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer). N Engl J Med 2005; 352:1851.
  17. Hampel H, Stephens JA, Pukkala E, et al. Cancer risk in hereditary nonpolyposis colorectal cancer syndrome: later age of onset. Gastroenterology 2005; 129:415.
  18. Codori AM, Brandt J. Psychological costs and benefits of predictive testing for Huntington's disease. Am J Med Genet 1994; 54:174.
  19. ACCE: A CDC-sponsored project carried out by the Foundation of Blood Research. Available at: www.cdc.gov/genomics/gtesting/ACCE/acce_proj.htm (Accessed on November 16, 2009).
  20. Clayton EW. Ethical, legal, and social implications of genomic medicine. N Engl J Med 2003; 349:562.
  21. Weil J. Psychosocial Genetic Counseling, Oxford University Press, New York 2000.
  22. Peters JA, Kenen R, Giusti R, et al. Exploratory study of the feasibility and utility of the colored eco-genetic relationship map (CEGRM) in women at high genetic risk of developing breast cancer. Am J Med Genet A 2004; 130A:258.
  23. Marteau TM, Croyle RT. The new genetics. Psychological responses to genetic testing. BMJ 1998; 316:693.
  24. Green RM, Thomas AM. Whose gene is it? A case discussion about familial conflict over genetic testing for breast cancer. J Genet Couns 1997; 6:245.
  25. Patenaude AF, Dorval M, DiGianni LS, et al. Sharing BRCA1/2 test results with first-degree relatives: factors predicting who women tell. J Clin Oncol 2006; 24:700.
  26. MacDonald DJ, Sarna L, van Servellen G, et al. Selection of family members for communication of cancer risk and barriers to this communication before and after genetic cancer risk assessment. Genet Med 2007; 9:275.
  27. Botkin JR, Belmont JW, Berg JS, et al. Points to Consider: Ethical, Legal, and Psychosocial Implications of Genetic Testing in Children and Adolescents. Am J Hum Genet 2015; 97:6.
  28. Rothenberg KH. Genetic information and health insurance: state legislative approaches. J Law Med Ethics 1995; 23:312.
  29. Pokorski RJ. A test for the insurance industry. Nature 1998; 391:835.
  30. Allain DC, Friedman S, Senter L. Consumer awareness and attitudes about insurance discrimination post enactment of the Genetic Information Nondiscrimination Act. Fam Cancer 2012; 11:637.
  31. Genetic Information Nondiscrimination Act (GINA). Public Law 110-233, 122 Stat. 881 (final passage May 21, 2008).
  32. Hudson KL, Holohan MK, Collins FS. Keeping pace with the times--the Genetic Information Nondiscrimination Act of 2008. N Engl J Med 2008; 358:2661.
  33. Korobkin R, Rajkumar R. The Genetic Information Nondiscrimination Act--a half-step toward risk sharing. N Engl J Med 2008; 359:335.
  34. Green RC, Lautenbach D, McGuire AL. GINA, genetic discrimination, and genomic medicine. N Engl J Med 2015; 372:397.
  35. http://www.genome.gov/10002077 (Accessed on October 11, 2013).
  36. https://www.disabilityrightslegalcenter.org/about/documents/GeneticsStateSurveyFinal.pdf (Accessed on October 11, 2013).
  37. Hall MA, Rich SS. Patients' fear of genetic discrimination by health insurers: the impact of legal protections. Genet Med 2000; 2:214.
  38. Hudson KL. Genomics, health care, and society. N Engl J Med 2011; 365:1033.
  39. Van Hoyweghen I, Horstman K. European practices of genetic information and insurance: lessons for the Genetic Information Nondiscrimination Act. JAMA 2008; 300:326.
  40. Godard B, Raeburn S, Pembrey M, et al. Genetic information and testing in insurance and employment: technical, social and ethical issues. Eur J Hum Genet 2003; 11 Suppl 2:S123.
  41. Lerman C, Shields AE. Genetic testing for cancer susceptibility: the promise and the pitfalls. Nat Rev Cancer 2004; 4:235.
  42. Morrison PJ. Insurance, unfair discrimination, and genetic testing. Lancet 2005; 366:877.
  43. Otlowski M, Taylor S, Bombard Y. Genetic discrimination: international perspectives. Annu Rev Genomics Hum Genet 2012; 13:433.
  44. Murashige N, Tanimoto T, Kusumi E. Fear of genetic discrimination in Japan. Lancet 2012; 380:730.
  45. US Department of Health, Education, and Welfare. The Institutional Guide to DHEW Policy on Protection of Human Subjects. GPO; US Department of Health, Education, and Welfare, Washington, DC 1971.
  46. Yang Y, Muzny DM, Reid JG, et al. Clinical whole-exome sequencing for the diagnosis of mendelian disorders. N Engl J Med 2013; 369:1502.
  47. GeneTests: Medical Genetics Information Resource (database online). Available at: www.ncbi.nlm.nih.gov/sites/GeneTests/?db=GeneTests (Accessed on November 09, 2009).
  48. Warby, SC, Graham, RK, Hayden, MR. Huntington Disease. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Available at: www.ncbi.nlm.nih.gov/bookshelf/br.fcgl?book=gene&part=huntington#huntington (Accessed on November 17, 2009).
  49. Dietz, HC. (Updated June 30, 2009). Marfan Syndrome. In: GeneReviews at GeneTests: Available at: www.ncbi.nlm.nih.gov/bookshelf/br.fcgl?book=gene&part=marfan#marfan (Accessed on November 17, 2009).
  50. Kujovic JL. Factor V Leiden Thrombophilia. In: GeneReviews at GeneTests. Available at: www.ncbi.nlm.nih.gov/bookshelf/br.fcgl?book=gene&part=factor-v-leiden#factor-v-leiden (Accessed on November 17, 2009).
  51. Kefford RF, Newton Bishop JA, Bergman W, Tucker MA. Counseling and DNA testing for individuals perceived to be genetically predisposed to melanoma: A consensus statement of the Melanoma Genetics Consortium. J Clin Oncol 1999; 17:3245.