This chapter explains the application of genetic medicine in childhood. It notes how patients and families with a family history of genetic disorders are identified with the help of genetic data. Moreover, the chapter looks at modes of inheritance by referencing Mendelian inheritance, autosomal recessive inheritance, and autosomal dominant inheritance. It also includes the underlying mutations linked with single gene disorders. The chapter then explores aneuploidy, the loss or gain of one or more whole chromosomes, alongside its structural chromosomal rearrangements. Finally, it tackles the clinical and ethical guidelines to genetic counselling and genetic testing as well.
The Application of Genetic Medicine in Childhood
Genetic Medicine for Adult Onset Disease
This chapter discusses genetic medicine for adult onset disease. It explores the concept of variable penetrance which is linked to expressivity. The chapter cites the process of using genetic testing for type 1 hereditary haemochromatosis. It also compares diseases with monogenic, polygenic, and multifactorial causes. Moreover, it looks at the differences between discontinuous traits and continuous traits. It then explores methods used to identify alleles with additive effects on complex disease phenotypes. The chapter also notes that polygenic risk score (PRS) is the probabilistic information achieved using information from all of the genome-wide association study (GWAS) genetic data points.
Barbara Jennings, Nandu Thalange, and Gavin Willis
Genetics in Medicine examines nucleic acids, genes, and genomes. It also discusses mutations and genetic variations. Next, it considers laboratory techniques and the sequencing revolution. The application of genetic medicine in childhood is also taken into consideration. Then, the text examines genetic medicine for adult onset disease. The book ends with a discussion of pharmacogenetics and personalized medicine.
Laboratory Techniques and the Sequencing Revolution
This chapter explores laboratory techniques and the sequencing revolution. It examines DNA structure and synthesis as they are applied to laboratory methods. An example is the polymerase chain reaction (PCR). The chapter then highlights how next generation sequencing (NGS) revolutionized molecular diagnostics. It notes the process of analysing DNA sequences to detect pathogenic variants. Moreover, the chapter compares whole genome sequencing and whole exome sequencing, which are both used to diagnose rare diseases. It emphasizes that molecular genetic tests could help diagnose diseases, choose medicine, and screen newborn infants for treatable conditions. The chapter also mentions bioinformatics, which is an emerging clinical science developed alongside the use of whole genome analysis.
Mutations and Genetic Variation
This chapter introduces mutations and genetic variation. It looks at how mutations could alter DNA sequences. A mutation is a rare heritable change in the nucleotide sequence. The chapter then notes the functional impact of mutations on phenotypes like genetic nomenclature, before comparing the impact of germline and somatic mutations on health and diseases. In addition, it presents key terms of genetic variants such as private mutation, rare variant, and polymorphism. It then examines the application of human genetic variation in medical practice. The chapter also considers genetic counselling and presents it as the communication of information and advice about inherited and other genetic conditions, which include taking a family history and constructing a pedigree diagram.
Nucleic Acids, Genes, and Genomes
This chapter examines the structure of the DNA molecule and its organization in line with chromosomes and the mitochondria of human cells. It explores the human genome and the organization of coding and non-coding DNA. Additionally, the chapter highlights the roles of the Human Genome Project (HGP) and spin-off projects in the progress of genetic medicine. It also compares the function of RNA molecules in the transcription and translation into protein sequences. It then tackles the regulation of gene expression which is the transmission of information from a DNA sequence that results in a gene product. Moreover, the chapter states that epigenetic changes can modify gene expression without an associated change in the DNA sequence.
Pharmacogenetics and Personalized Medicine
This chapter presents pharmacogenetics and personalized medicine. It defines pharmacodynamics as being concerned with the effects of drugs on target cells and tissues, while pharmacokinetics is the study of the movement of drugs on target cells and tissues. The chapter discusses the adverse impact and ethical principle of a doctor's oath of doing no harm. It highlights the actionable mutations in the development of cancer and companion diagnostics. The chapter also explores pharmacogenomics. It cites the benefits and issues of treatment stratification and personalized medicine. Lastly, it notes that data about the biomarkers can be collected from tests of individual loci and gene panels, or whole genome analysis.