Welti J, Loges S, Dimmeler S, et al: Recent molecular discoveries in angiogenesis and anti-angiogenesis therapies in cancer, J Clin Invest 123:3190–3200, 2013. [A discussion of angiogenic mechanisms and successes and challenges of anti-angiogenic therapy in cancer.]
White E: The role of autophagy in cancer, J Clin Invest 125:42–46, 2016. [A discussion of the diverse possible contributions of autophagy to cancer.] http://ebooksmedicine.net studentconsult.com
MendelianDisorders:DiseasesCausedbySingle-GeneDefects
Transmission Patterns of Single-Gene Disorders
General Features of Chromosomal
Diseases Caused by Alterations of Imprinted Regions: Prader-Willi and Angelman Syndromes
Molecular Diagnosis of Copy Number Abnormalities
Direct Detection of DNA Mutations by Polymerase Chain Reaction (PCR) Analysis
The completion of the human genome project was a landmark achievement in the study of human diseases. It established that humans have only about 25,000 protein-coding genes, far fewer than the 100,000 previously estimated and almost half the number in the lowly rice plant (Oryza sativa)! The unraveling of this “genetic architecture” is beginning to unlock secrets of inherited as well as acquired human disease. Powerful technologies now allow applications of the human gene sequences to the analysis of human diseases. Current high-throughput “next-generation” sequencing technologies can routinely sequence the human exome (the entire compendium of coding genes) in a couple of days for as little as $1000. The speed and reduced costs of DNA sequencing are increasingly facilitating the application of “personalized medicine” (also known as “precision medicine”) to the treatment of cancer and other diseases with a genetic component.
Because disorders of childhood are of genetic origin, developmental and pediatric diseases are discussed along with genetic diseases in this chapter. However, it must be borne in mind that not all genetic disorders manifest in infancy and childhood, and conversely, many pediatric diseases are not of genetic origin. To the latter category belong diseases resulting from immaturity of organ systems. In this context it is helpful to clarify three commonly used terms: hereditary, familial, and congenital. Hereditary disorders, by definition, are derived from one’s parents, are transmitted in the gametes through the generations, and therefore are familial. The term congenital simply implies “present at birth.” Of note, some congenital diseases are not genetic (e.g., congenital syphilis). On the other hand, not all genetic diseases are congenital; the expression of Huntington disease, for example, begins only after the third or fourth decade of life.
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There are several types of genetic abnormalities that affect the structure and function of proteins, disrupting cellular homeostasis and contributing to disease.
The term mutation refers to permanent changes in the DNA. Those that affect germ cells are transmitted to the progeny and may give rise to inherited diseases. Mutations in somatic cells are not transmitted to the progeny but are important in the causation of cancers and some congenital malformations.
Details of specific mutations and their effects are discussed along with the relevant disorders throughout this book. Cited here are some common examples of gene mutations and their effects: