The Busy Physician's Guide to Genetics, Genomics and Personalized Medicine

PREFACE. INTRODUCTION. 1 GENETIC VARIABILITY PROVIDES THE BIOCHEMICAL BASIS FOR OUR INDIVIDUALITY, INCLUDING DIFFERENCES IN OUR SUSCEPTIBILITY TO MANY COMMON DISEASES. 1.1 Defining And Differentiating Between Genetics And Genomics. 1.2 The Structure Of DNA, The Variability Of The DNA Sequence And The Independent Inheritance Of Gene Alleles By Siblings. 1.3 A Review Of The Process Whereby A Gene Makes Its Protein. 1.4 A Typical Gene's Sequence And The Level Of Activity In The Associated Protein Are As Variable As Any Other Human Biological Trait. 1.5 Risk-Increasing Alleles Have Variable Frequencies And Variable Levels Of Penetrance. 1.6 Polymorphisms In Promoter Regions And Other Non-Coding Sequences Influence The Activity Of Our Proteins. 1.7 Epigenetic Factors Also Control Gene Activity. 1.8 Common Types Of Variants In The Human DNA Sequence . 1.9 Common Multifactorial Diseases Are Genetic Disorders, Despite Their Non-Mendelian Patterns Of Inheritance. 1.10 Personalized Medicine Testing May Allow You To Better Tailor The Treatment To The Individual, And May Allow The Individual To Make Healthier Choices. 2 MAKING THE MOST OF FAMILY HISTORY INFORMATION, SINGLE GENE DISORDERS AND MENDELIAN PATTERNS OF INHERITANCE, AND WHEN TO REFER TO A GENETIC SPECIALIST. 2.1 Maximizing The Use Of Family Medical History In Disease Risk Assessment. 2.2 Single Gene Disorders. 2.3 Understanding Mendelian Patterns Of Inheritance (Single Gene Disorders). 2.4 Assessing The Risk Of Recurrence In Mendelian Pedigrees. 2.5 Carrier Frequencies For The More Common Recessive Single-Gene Disorders. 2.6 Referring To A Genetic Specialist. 2.7 New Genomic Applications For Complex Disease Will Change Approaches To Genetic Counseling and Personalized Medicine. 3 TYPES OF GENETIC TESTS AND ISSUES ASSOCIATED WITH THE INTERPRETATION OF THEIR RESULTS. 3.1 Accessing Current Information On Available Genomic Medicine Tests. 3.2 Standard Format For Genetic Test Results. 3.3 Risk-Increasing Gene Alleles Often Have Limited Penetrance. 3.4 The ACCE And EGAPP Projects Evaluate Emerging Genetic Tests. 3.5 Assessing The Usefulness Of A Genomic Test. 3.6 Even An Informative Genetic Test May Have Limited Clinical Utility. 3.7 Single Nucleotide Polymorphisms (SNPs) Are The Most Commonly Tested Polymorphisms. 3.8 There Are Many Small Deletions And Insertions In Different People's DNA. 3.9 Repeated Sequence Length Polymorphisms And Microsatellite Analysis. 3.10 Chromosome Rearrangements Can Contribute To Some Complex Disorders. 3.11 Copy Number Variation Is Surprisingly Frequent. 3.12 It Is Sometimes Necessary To Determine The Level Of Activity In Specific Genes. 3.13 Mitochondrial DNA Variants Are Also Relevant. 3.14 Many Epigenetic Factors That Influence Gene Activity Are Amenable To Testing. 3.15 Some Tests Assess Characteristics Of The Pathogen. 3.16 Cancer Analyses Often Must Include Somatic Mutations As Well As Germline Mutations. 3.17 Predictive Algorithms Must Include Both Genetic And Nongenetic Factors. 3.18 Genome-Wide Association (GWA) Studies Provide Insights Into The Mechanisms For Disease, But Their Results Are Often Not Clinically Useful. 3.19 A Brief Introduction To The Most Important Technological Advances. 4 TOWARD THE SAFER AND MORE EFFECTIVE USE OF PRESCRIPTION DRUGS: PHARMACOGENETICS. 4.1 Genetic Polymorphisms Affect Both The Pharmacokinetics And Pharmacodynamics Of Many Prescription Drugs. 4.2 Improving On The Disease-Oriented Approach To Prescribing Drugs. 4.3 Limitations Of Genetic Testing. 4.4 Dose-Calculating Algorithms Must Take Genetic And Nongenetic Factors Into Account. 4.5 Epigenetic Factors Must Be Factored Into Many Algorithms As Well. 4.6 Polymorphisms In The CYP450 Genes Influence The Pharmacokinetics Of Many Commonly Prescribed Drugs.4.7 Other Functional Polymorphisms That Affect The Pharmacokinetics Of Multiple Drugs. 4.8 Polymorphisms In The Genes Encoding Beta-Adrenergic Receptors Influence The Pharmacodynamics Of Beta-Blockers. 4.9 Keepin