Molecular genetics and the skin

Published on 04/03/2015 by admin

Filed under Dermatology

Last modified 04/03/2015

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Molecular genetics and the skin

Recent and rapid advances in genetics have had an impact on our understanding of skin diseases. The Human Genome Project has now mapped all human genes, of which there are about 35 000. Genetics has been found to be more complicated than the original Mendelian concept, and common conditions such as atopy occur as a result of a complex interaction between multiple susceptibility genes and the environment. An average pregnancy carries a 1% risk of a single gene disease and a 0.5% risk of a chromosome disorder, but genetically influenced traits, e.g. atopy, are much more common.

The human chromosomes

The human genome comprises 23 pairs of chromosomes that are numbered by size (Fig. 1). Chromosomes are packets of genes with support proteins in a large complex. The karyotype is an individual’s number of chromosomes plus their sex chromosome constitution, i.e. 46XX for females and 46XY for males. The phenotype is the expression at a biological level of the genotype, e.g. blue eyes or atopy.

Molecular methods

DNA sequence variations can be identified by the consequent change in polymerase chain reaction (PCR) amplification product size (Fig. 2), loss or gain of restriction endonuclease cutting, or sequence analysis. In recent years, DNA sequencing has become a high-throughput technology that has led to the concept of ‘whole genome sequencing’ studies of healthy versus controls. As this technique is so powerful, smaller numbers are required.

To establish which molecular pathways may be important in disease pathogenesis, gene chip arrays and ‘next generation sequencing’ allow detailed and quantitative analysis of the transcribed genes in a diseased tissue (transcriptome). The transcribed genes are subject to further regulation by RNA degradation, silencing and inhibition. Thus, study of the protein repertoire in the diseased tissue (proteomics) may also be undertaken.

Molecular techniques can be used to:

Table 1 Skin conditions or characteristics with definite or probable gene localities on the chromosomes

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Chromosome site Disease or characteristic
1p34 Porphyria cutanea tarda: enzyme (p. 46)
2q31 Ehlers–Danlos syndrome: collagen III (p. 93)
3p21.3 Dystrophic epidermolysis bullosa: collagen VII (p. 91)
4, 4p Red hair colour, psoriasis (Psors3 gene)
6p21.3 Psoriasis (Psors1 gene: 30% of susceptibility)
9p21