RT Book, Section A1 McCarthy, Jeanette J. A1 Mendelsohn, Bryce A. SR Print(0) ID 1134734837 T1 The Genetic Basis of Disease T2 Precision Medicine: A Guide to Genomics in Clinical Practice YR 2016 FD 2016 PB McGraw-Hill Education PP New York, NY SN 9781259644139 LK accessmedicine.mhmedical.com/content.aspx?aid=1134734837 RD 2024/03/29 AB The average human has approximately 4 million germline variants, that is, positions in their genome that differ from the reference genome (see Appendix 2 for a discussion of the reference genome). For the most part, this variation is not harmful and makes us distinct individuals, but some variants have been linked to diseases and health-related traits. The presence of some disease-causing variants means a high degree of certainty that the person with the variant will develop the disease. This is true for so-called Mendelian diseases. For other disease-causing variants, the relationship with disease is complex and the variants not very predictive of disease. Establishing the relationship between a genetic variant and disease is accomplished through different research methods. Mendelian and complex diseases differ in terms of the location of disease-causing variants, their frequency in the population, their penetrance, and their utility as diagnostic/predisposition tests.