The busy physician's guide to genetics, genomics and personalized medicine [electronic resource] / Kevin M. Sweet, Ron C. Michaelis
- Author
- Sweet, Kevin M.
- Published
- Dordrecht ; New York : Springer, [2011]
- Copyright Date
- ©2011
- Physical Description
- 1 online resource (xxiv, 211 pages) : illustrations
- Additional Creators
- Michaelis, Ron C.
Access Online
- SpringerLink: ezaccess.libraries.psu.edu
- Contents
- Machine generated contents note: 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 -- 1.2.1.The Structure of DNA -- 1.2.2.The Arrangement of Genes on Chromosomes -- 1.2.3.The Polymorphic Human DNA Sequence: Gene Alleles, Protein Isoforms and Genotypes -- 1.2.4.Each Sibling Inherits a Unique Combination of Gene Alleles from the Parent -- 1.3.A Review of the Process Whereby a Gene Makes Its Protein -- 1.3.1.Coding Sequences and Regulatory Sequences -- 1.3.2.Transcription: Deoxyribonucleic Acid (DNA) Makes Ribonucleic Acid (RNA) -- 1.3.3.Posttranscriptional RNA Processing -- 1.3.4.Translation of mRNA into a Polypeptide -- 1.3.5.The Genetic Code and the Structures of Our Amino Acids -- 1.3.6.Posttranslational Processing of the Polypeptide -- 1.4.A Typical Gene's Sequence and the Level of Activity in the Associated Protein Are as Variable as Any Other Human 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 -- 1.6.1.Polymorphisms in Promoter Regions Alter the Gene's Level of Activity -- 1.6.2.Chromosome Rearrangements Can Cause Promoters to Drive Transcription of the Wrong Sequences -- 1.6.3.Intronic Gene Variants That Influence RNA Splicing or Gene Activity May Be Unrecognized Risk Factors -- 1.6.4.Intronic Polymorphisms Can Influence the Ratio of Protein Isoforms or the Balance of Allelic Expression -- 1.6.5.Interfering RNAs Exert an Important Influence over Gene Activity -- 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 -- 1.11.Summary -- Further Readings -- 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) -- 2.3.1.Autosomal Dominant Inheritance -- 2.3.2.Autosomal Recessive Inheritance -- 2.3.3.X-linked Recessive -- 2.3.4.X-linked Dominant Inheritance -- 2.3.5.Y-Linked Inheritance -- 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 -- Selected References -- 3.Types of Genetic Tests and Issues Associated with the Interpretation of Their Results -- 3.1.Accessing Current Information on Available Personalized 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 Genetic 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 -- 3.9.1.The Repeated Sequence Motif Can Vary in Length -- 3.9.2.Microsatellite Instability (MSI) Is Observed in Certain Types of Cancer -- 3.9.3.Loss of Heterozygosity (LOH) of Microsatellites Is Seen in Several Disorders -- 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 -- 3.18.1.Direct-to-Consumer GWA Testing Services May Provide Results That Have Limited Clinical Utility -- 3.18.2.GWA Studies Identify Risk-Increasing Alleles, But Have Their Limitations -- 3.18.3.Measures of the Association Between the Risk-Influencing Allele and the Disorder/ADR -- 3.18.4.Many of the SNPs That Are Used in GWA Studies Are Not Themselves Functional Polymorphisms, But Are Linked to Functional Polymorphisms -- 3.18.5.Haplotype Blocks in the Human Genome Increase the Efficiency of GWA Studies -- 3.18.6.Internet Resources That Summarize Findings from GWA Studies -- 3.19.A Brief Introduction to the Most Important Technological Advances -- 3.19.1.The Polymerase Chain Reaction (PCR) Allows One to Isolate the Sequence of Interest; Many Assays Begin with the PCR -- 3.19.2.Microarray Analyses Have Greatly Accelerated the Pace of Discovery -- 3.19.3.Sequencing Provides Maximum Information, and Will Revolutionize Clinical Diagnostics -- 3.19.4.There Are Several Techniques Commonly Used to Assess Status for a SNP -- 3.19.5.PCR Simplifies Analysis of Indels and Length Polymorphism and Detection of MSI and LOH -- 3.19.6.Hybridization Techniques Detect CNVs -- 3.19.7.Reverse Transcription-PCR Measures the Level of Activity in a Gene -- 3.19.8.Immunohistochemical (IHC) Analyses Allow Direct Visualization of the Protein -- 3.19.9.Expression Arrays Reveal Disease-Associated and Treatment-Associated Changes in Gene Expression -- 3.19.10.Some Epigenetic Factors Can Be Easily Assessed -- 3.19.11.G-Banding Allows the Detection of Chromosome Rearrangements -- Further Readings -- 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 -- 4.6.1.The CYP450 Enzymes Metabolize Many Commonly Prescribed Drugs -- 4.6.2.Defining the Metabolizer Phenotype by Assessing CYP450 Status -- 4.7.Other Functional Polymorphisms That Affect the Pharmacokinetics of Multiple Drugs -- 4.7.1.N-Acetyltransferase 2 -- 4.7.2.Butyrylcholinesterase -- 4.7.3.Functional Polymorphisms in Drug Transporter Genes also Affect the Response to Many Drugs -- 4.8.Polymorphisms in the Genes Encoding Beta-Adrenergic Receptors Influence the Pharmacodynamics of Beta-Blockers -- 4.9.Keeping up to Date with FDA Approvals and the Status of the Field -- Further Readings -- 5.Taking a Personalized Medicine Approach to Breast and Colon Cancer -- 5.1.Cancer Is a Complex Genetic Disease -- 5.2.Breast Cancer Gene Variants with Low Penetrance -- 5.3.Further Research Will Increase Accuracy and Standardize Risk-Estimating Algorithms -- 5.4.Useful Online Programs to Calculate Breast Cancer Risk -- 5.5.Highly Penetrant Breast Cancer Gene Variants -- 5.6.Hereditary Breast-Ovarian Cancer Syndrome -- 5.7.BRCA Gene Testing -- 5.8.Effects of Possessing Risk-Increasing BRCA Alleles -- 5.9.Cancer Screening and Prevention Measures for Female BRCA Variant Carriers -- 5.10.BRCA Mutation Positive Case Study -- 5.10.1.Mrs. C's Initial Meeting with the Genetic Counselor -- 5.10.2.Interpreting the Test Results and Following Them Up -- 5.10.3.The Plans for Mrs. C and Her Family Members -- 5.10.4.Further Developments -- 5.11.Colon Cancer Gene Variants with Low Penetrance -- 5.12.Highly Penetrant Colorectal Cancer Gene Variants -- 5.13.Lynch Syndrome -- 5.14.Molecular Genomic Testing in Patients Suspected of Having Lynch Syndrome -- 5.14.1.Microsatellite Instability (MSI) Is a Hallmark of Lynch Syndrome -- 5.14.2.Some Labs Offer Complementary MSI and IHC Analyses -- 5.15.Cancer Screening and Prevention Measures for LS Mutation Carriers -- 5.16.Familial Adenomatous Polyposis -- 5.17.APC Mutation Screening in Familial Adenomatous Polyposis -- 5.18.Cancer Screening and Prevention Measures for APC Mutation Carriers -- 5.19.Personalizing Drug Therapy for Cancer Patients -- 5.19.1.Gene Expression Assays can Classify Cancers into Molecular Subtypes -- 5.19.2.Several Gene Polymorphisms Affect Activity in Signal Transduction Pathways -- 5.19.3.Glioblastomas with MSH6 Mutations Resist Alkylating Agents -- 5.19.4.Pharmacokinetically Relevant Gene Polymorphisms Influence Drug Response, Especially the Risk for ADRs -- 5.19.5.HLA Type May Influence the Risk for Hypersensitivity Reactions After Abacavir -- Further Readings -- 6.Personalizing Risk Assessments and Treatments for Complex Cardiovascular Disease -- 6.1.Cardiovascular Diseases Are Complex, Multifactorial Diseases with Highly Variable Phenotypes -- 6.2.Family History and CVD Risk -- 6.3.Useful Online Programs to Estimate Heart Disease Risk -- 6.4.CVD-Associated Gene Variants Have Been Particularly Difficult to Identify -- 6.5.Most CVD-Associated Gene Variants Have Low Penetrance -- 6.5.1.A Cluster of Linked Markers in 9p21.3 Are Associated with Several CVDs -- and Contents note continued: 6.5.2.Other Low-Penetrance Variants That Influence Risk for CVD -- 6.6.Low-Penetrance Gene Variants That Affect Predisposing Phenotypes -- 6.6.1.Low-Penetrance Gene Variants That Alter Blood Lipid Levels -- 6.6.2.Sodium/Potassium Regulation and Essential Hypertension -- 6.6.3.Cardiac Channelopathies -- 6.6.4.Variants That Influence the Inflammation Response Influence Risk for CVDs -- 6.6.5.Genetic Variants Influence the Level of Oxidative Stress -- 6.6.6.Plasma Homocysteine Levels Influence Risk for CVD -- 6.6.7.Knowing They Possess Low-Penetrance Variants May Motivate Patients' Behavior -- 6.7.Case Report - Genetic Testing in a Patient with Type 2 Diabetes (T2D) and a Family History of Myocardial Infarction (MI) -- 6.7.1.Jameer's Initial Visit -- 6.7.2.Meeting with the Cardiologist and Genetic Counselor -- 6.7.3.The Plan for Follow-Up -- 6.8.CVD Gene Variants with High Penetrance: Familial Hypercholesterolemia (FH) -- 6.8.1.FH Is Often Underdiagnosed -- 6.8.2.Highly Penetrant FH Gene Variants -- 6.9.Molecular Genomic Testing in Patients Suspected of Having FH -- 6.10.CVD Gene Variants with High Penetrance: Hypertrophic Cardiomyopathy (HCM) -- 6.10.1.The HCM Phenotype Is Highly Variable -- 6.10.2.Highly Penetrant Gene Variants That Increase Risk for HCM -- 6.11.Therapy and Prevention Measures for HCM Mutation Carriers -- 6.12.Genes Influencing the Risk for Other Cardiomyopathies -- 6.13.Cardiovascular Pharmacogenomics -- 6.13.1.The CYP450 Enzymes Metabolize Several Drugs That Are Prescribed for CVDs -- 6.13.2.The Pharmacogenomics of Cholesterol-Lowering Drugs -- 6.13.3.Pharmacogenomic Testing Is Particularly Important for Patients Taking Warfarin -- 6.13.4.The Pharmacogenomics of Antihypertensive Drugs -- 6.13.5.Plasma Homocysteine Levels Influence Pyridoxine Response -- 6.13.6.CYPC19 Testing for Patients Prescribed Clopidogrel -- Further Readings -- 7.Other Multifactorial Disorders for Which Genetic/Genomic Testing Is Providing Insights -- 7.1.Age-Related Macular Degeneration -- 7.2.Type 2 Diabetes -- 7.2.1.GWA Studies Have Identified Several Genetic Markers That Increase Risk for T2D -- 7.2.2.The Currently Available Predictive Tests Do Not Include Genetic Markers -- 7.2.3.The Pharmacogenomics of Type 2 Diabetes -- 7.3.Personalizing the Approach to Psychiatric Disorders -- 7.3.1.Many Original Findings Must Be Confirmed -- 7.3.2.Testing Genetic Variants That Influence Pharmacokinetics Is Helpful in the Treatment of Some Psychiatric Disorders -- 7.3.3.Some Associations with Attention Deficit-Hyperactivity Disorder (ADHD) Have Been Confirmed -- 7.3.4.Polymorphisms in Genes That Influence Serotonergic and Dopaminergic Function May Influence Personality -- 7.3.5.Copy Number Variation May Influence the Risk for Schizophrenia -- 7.3.6.Several Polymorphisms May Influence the Risk for Schizophrenia and the Response to Antipsychotic Drugs -- 7.3.7.Several Polymorphisms Have Been Associated with Depression and Bipolar Disorder (BPD) -- 7.3.8.Polymorphisms in the Serotonin Transporter (5HTT) Gene May Not Influence One's Risk for Depression After All -- 7.3.9.Polymorphisms in the Monoamine Oxidase a (MAOA) Gene May Not Influence the Propensity toward Antisocial Behavior after All -- 7.3.10.Anxiety Disorders -- 7.4.Personalizing the Treatment for Substance Abuse -- 7.4.1.Most Studies Have Focused on Catecholamine and Opiate Pathways -- 7.4.2.Stimulants -- 7.4.3.Alcohol -- 7.4.4.Opiates -- 7.4.5.Nicotine -- 7.5.Alzheimer Disease and Cognitive Decline in Aging -- 7.5.1.The ApoE Gene Is a Known Risk Factor -- 7.5.2.Other Gene Variants That Influence Risk for AD and Cognitive Decline in the Elderly -- 7.6.Asthma and Other Respiratory Disorders -- Further Readings.
- Subject(s)
- ISBN
- 9789400711471 (electronic bk.)
9400711476 (electronic bk.) - Note
- AVAILABLE ONLINE TO AUTHORIZED PSU USERS.
- Bibliography Note
- Includes bibliographical references and index.
View MARC record | catkey: 7288106