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In the 30 years since the first human gene, placental lactogen, was cloned in 1977, huge investments in time, money, and effort have gone into disclosing the innermost workings of the human genome. The Human Genome Project, which began in 1990, has led to sequence information on more than 3 billion base pairs (bp) of DNA, with identification of most of the estimated 25,000 genes in the entire human genome.1 Although a few relatively small gaps remain, the near completion of the entire sequence of the human genome is having a huge impact on both the clinical practice of genetics and the strategies used to identify disease-associated genes. Laborious positional cloning approaches and traditional functional studies are gradually being transformed by the emergence of new genomic and proteomic databases.2 Some of the exciting challenges that clinicians and geneticists now face are determining the function of these genes, defining disease associations and, relevant to patients, correlating genotype with phenotype. Nevertheless, many discoveries are already influencing how clinical genetics is practiced throughout the world, particularly for patients and families with rare, monogenic inherited disorders. The key benefits of dissection of the genome thus far have been the documentation of new information about disease causation, improving the accuracy of diagnosis and genetic counseling, and making DNA-based prenatal testing feasible.3 Indeed, the genetic basis of more than 2,000 inherited single gene disorders has now been determined, of which about 25% have a skin phenotype. Therefore, these discoveries have direct relevance to dermatologists and their patients. Recently, studies in rare inherited skin disorders have also led to new insight into the pathophysiology of more common complex trait skin disorders.4 This new information is expected to have significant implications for the development of new therapies and management strategies for patients. Therefore, for the dermatologist understanding the basic language and principles of clinical and molecular genetics has become a vital part of day-to-day practice. The aim of this chapter is to provide an overview of key terminology in genetics that is clinically relevant to the dermatologist.

Normal human beings have a large complex genome packaged in the form of 46 chromosomes. These consist of 22 pairs of autosomes, numbered in descending order of size from the largest (chromosome 1) to the smallest (chromosome 22), in addition to two sex chromosomes, X and Y. Females possess two copies of the X chromosome, whereas males carry one X and one Y chromosome. The haploid genome consists of about 3.3 billion bp of DNA. Of this, only about 1.5% corresponds to protein-encoding exons of genes. Apart from genes and regulatory sequences, perhaps as much as 97% of the genome is of unknown function, often referred to as “junk” DNA. However, caution should be exercised in labeling the noncoding genome as “junk,” because other unknown functions may reside in these regions. Much of the noncoding DNA is in the form of repetitive sequences, pseudogenes (“dead” copies of genes lost in recent ...

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