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.

Fig. 1 Chromosome 2.

Divided by the centromere into the shorter (p) and the longer (q) arms, showing banding with the Giemsa stain.

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.

Fig. 2 Agarose gel electrophoresis, showing migration of DNA after cutting with enzymes, screening for mutations in a keratin gene.

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:

detect small amounts of DNA, e.g. of human papilloma virus within a skin cancer

sequence DNA from a ‘candidate’ section of an individual’s chromosome and compare the base sequences with family members similarly affected by a disorder, thus mapping a specific gene polymorphism characteristic for that disease (Table 1)

sequence the entire genome of an individual

identify the repertoire of genes that have been transcribed as a measure of the protein profile of the cell.

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

Buy Membership for Dermatology Category to continue reading. Learn more here

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