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single nucleotide polymorphism (SNP) arrays, next-generation sequencing, chromatin conformation capture (3C), ATAC-Seq (assay for transposase-accessible chromatin with high throughput sequencing), CRISPR/Cas gene editing, induced pluripotent stem cell (iPSC)



  • 25% of monogenic gene disorders with known molecular mechanisms have skin manifestations.

  • Skin disease may also arise from polygenic, complex inheritance, mosaicism, and chromosomal abnormalities.

  • It is crucial for dermatologists to be up-to-date with new methods of genetic diagnosis and treatment (as well as their limitations).


The completion of the Human Genome Project in 2003 coincided with the dawn of the Information or Digital Age. Having sequenced more than 3 billion base pairs (bp) of DNA, with identification of most of the estimated 25,000 genes in the entire human genome, this initiative provided ourselves with a treasure trove of information to make sense of the human body and its diseases. 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.1 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.2 Indeed, the genetic basis of more than 2000 inherited single gene disorders has now been determined, of which about 25% have a skin phenotype. Therefore, these “genodermatoses” have direct relevance to dermatologists and their patients, and newer technologies such as whole-exome sequencing will identify even more single-gene disorders and even allow us to classify them according to their patient-specific mutations.3 Recently, studies in rare inherited skin disorders have also led to new insight into the pathophysiology of more common polygenic skin disorders.4 This new information is expected to have significant implications for the development of new therapies and management strategies for patients. Therefore, understanding the basic language and principles of clinical and molecular genetics has become a vital part of day-to-day practice for clinicians. The aim of this chapter is to provide an overview of key terminology in genetics that is clinically relevant to dermatologists.


Humans have a large complex genome packaged in the form of 46 chromosomes. These consist of 22 pairs of autosomes, numbered in descending order ...

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