FIGURE 3.3

Normal male karyotype.

FIGURE 3.6

Types of gene change and methods for their detection. PCR = polymerase chain reaction.

FIGURE 3.8

Chromosomes 8 and 9 from an individual with a reciprocal 8;9 translocation: 46,XX,t(8:9)(q24.1;q22.1).

FIGURE 3.10

Fluorescence in-situ hybridization allows detection of the presence of specific genes. The principle of the technique is illustrated.

FIGURE 3.11

(A) FISH with a probe to the HER2 gene shows the usual two copies of the HER2 gene (red signals) and two copies of the control probe (green signal) in each cell. (B) Immunohistochemistry on this tumour with a normal HER2 gene complement shows little expression of the epidermal growth factor receptor, which is encoded by the HER2 gene. (C) FISH shows many copies of the HER2 gene in each cell. (D) Immunohistochemistry on this tumour shows over-expression of the epidermal growth factor receptor, localized to the cell surface. Tumours showing overexpression of HER2 show an improved prognosis following treatment with Trasumatab (Herceptin ™). (Images provided by Dr Lee Jordan, Department of Pathology, Ninewells Hospital and Medical School.)

FIGURE 3.12

Drawing a family tree. A pedigree is drawn using standard symbols.

FIGURE 3.13

The three most common patterns of single gene inheritance for human disease. (A) Autosomal dominant inheritance; (B) autosomal recessive inheritance; and (C) X-linked recessive inheritance.

FIGURE 3.14

X-inactivation. (A) Normal female. (B) Female carrier of mutation on X chromosome.

FIGURE 3.15

Gene structure and how a protein is encoded.

FIGURE 3.16

A plaque-like carcinoma in Transverse colon. (Image provided by Professor Jeremy Jass.)

FIGURE 3.17

Family tree of the patient.

FIGURE 3.19

Loss of the sole functioning copy of the MLH1 gene during somatic cell division makes a colonic epithelial cell prone to developing further mutations. HNPCC = hereditary non-polyposis colorectal cancer.

FIGURE 3.20

Analysis of microsatellite ‘BAT25’ in DNA from the patient. Microsatellites are short stretches of repetitive DNA that vary in length between individual copies of the genome. Analysis of DNA extracted from blood from the individual showed two different microsatellite lengths (shaded in the figure), reflecting the two copies of the genome in a diploid individual. Analysis of DNA extracted from the tumour showed multiple different lengths of microsatellite. This occurs because loss of the sole functional copy of MLH1 causes failure of mismatch repair and the microsatellite length can change during cell division in multiple cell lineages in the tumour. The tumour is said to show ‘microsatellite instability’.

FIGURE 3.21

(A) Poorly differentiated adenocarcinoma of colon with chronic inflammatory reaction. (B) Staining for MSH2 shows presence of protein in tumour cells and inflammatory cells. (C) Staining for MLH1 shows loss of staining in tumour cells. Chronic inflammatory cells remain positive, providing an internal control. (D) Staining for PMS2 shows loss of protein. This occurs because PMS2 is stabilized by forming a complex with MLH1, which cannot take place when MLH1 expression is lost. Chronic inflammatory cells remain positive, acting as a positive internal control.

FIGURE 3.22

Skin of patient with ichthyosis vulgaris showing fine scaling and flaking. (Courtesy of Professor Colin Munro).

FIGURE 3.23

(A) Normal skin and (B) skin from a patient with ichthyosis vulgaris showing loss of normal keratinization in the upper epidermis.

FIGURE 3.24

Immunohistochemical staining for filaggrin in (A) normal skin and (B) skin from a patient with ichthyosis vulgaris. There is no staining for the filaggrin protein in the upper epidermis from the patient, because the patient is homozygous for the R501X mutation in the filaggrin gene, abolishing protein production. (Courtesy of Professor McLean.)