Biology of Disease

Dominant genes are conventionally written as an upper case italic letter, for

exampleG, while its recessive counterpart is given the lower case form, g.

Figure15.10 (A) illustrates the normal inheritance pattern first established by

Mendel (1822–1884). If one parent is homozygous for an autosomal dominant

gene (GG) and the other parent is homozygous for the recessive form (gg),

then all the offspring will be genetically heterozygous (Gg) and phenotypically

will express the dominant trait. If both parents are heterozygotes (Figure

15.10 (B)), then 25% of offspring will be homozygous for the dominant gene

(GG), 25% homozygous for the recessive gene (gg) and the remaining 50% of

offspring will be heterozygous (Gg).

X]VeiZg&*/ GENETIC DISEASES

)'' W^dad\nd[Y^hZVhZ

Figure 15.10 The inheritance patterns shown for a single pair of genes between (A) two contrasting homozygous

parents and (B) two heterozygous parents.

Mutations are changes that occur in the genome and can give rise to clinical

disorders (Margin Note 15.2). Mutations include changes within single genes

and changes to whole chromosomes. They may be simple substitutions of one

nucleotide for another (point mutations), involve the insertion or deletion

of one or more nucleotides within the normal sequence of DNA within a

chromosome or even alter the structures of individual chromosomes or the

number of chromosomes present. When considering the effects of mutations,

it is important to distinguish between a genetic change which occurs in somatic

cells and one occurring in gametes. Mutations arising in somatic cells will not

be transmitted to future generations although they may represent the first step

in the development of cancer (Chapter 17). In somatic cells, mutations that

produce a recessive autosomal allele are unlikely to have clinical consequences

because their expression is masked by the corresponding dominant allele.

However, somatic mutations that are dominant or X-linked (see below) can

have a greater impact because they are likely to be expressed. Similarly, their

impact is greater if they arise early in development before undifferentiated

cells give rise to differentiated tissues or organs. In adult tissues, the activities

of many nonmutant cells often mask mutations in a few other cells. Mutations

in gametes or gamete forming tissues are part of the germ line (Chapter 17)

and are of greater clinical concern because as well as affecting that individual,

they will also be transmitted to offspring.

Dominant autosomal mutations M will be expressed phenotypically in both the

homozygous and heterozygous condition. However, if the mutation is recessive

(m) then it is not likely to affect an individual unless both chromosomes carry

Margin Note 15.2 The human

genome

The genome is the complete sequence

of bases in the DNA molecules,

which is all of the hereditary material

possessed by an individual. The

human haploid genome contains

about 3 000 000 000 pairs of

nucleotides. The total length of this

DNA is about a meter and is divided

into 23 individual molecules; 22 of

which are found in the autosomes

and one in the sex chromosome.

Mitochondrial DNA contains 37

genes.

i

Parents

Gametes

Offspring

Gametes

Offspring

Parents

A) B)

GG

Gg Gg

gg

Gg Gg

x

G G

Gg

GG Gg

Gg

Gg gg

x

g g G g G g

50% are

heterozygous

All offspring genetically heterozygous

and will express the dominant trait

25% are

homozygous

for dominant

trait

25% are

homozygous

for recessive

trait

G

g

Dominant allele of gene

Recessive allele of gene