Biology of Disease

DETECTING, DIAGNOSING AND SCREENING HUMAN GENETIC DISEASES

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Second division

disjunctionNormal nondisjunction

Normal

disjunction

B)

X

Haploid

gamete

Disomic

(normal)

Disomic

(normal)

Trisomic Monosomic

First division

nondisjunction

disjunctionNormal

A)

X

Haploid

gamete

Trisomic Trisomic Monosomic Monosomic

Figure 15.36 Schematic to show the production of abnormal gametes following nondisjunction at (A) at meiosis I and (B) meiosis II
resulting in trisomic zygotes following fertilization with a normal haploid gamete.

15.10 DETECTING, DIAGNOSING AND SCREENING HUMAN
GENETIC DISEASES

Identifying the genetic basis for a human disorder usually requires an analysis
of the family history as far back as possible. If this shows that the trait is
inherited, it is possible to predict whether the mutant allele is dominant
or recessive and whether it is X- or autosomal-linked. Obviously, dominant
mutations are the simplest to detect. If they are X-linked, then affected fathers
will pass the trait to all their daughters. However, if autosomal, then dominant
mutations would be expected to occur in approximately 50% of the children
of an affected heterozygous individual.

In many cases, the diagnosis of a genetic disease can be made prenatally. The
most widely used methods for this are amniocentesis and chorionic villus
sampling (CVS). In the former, a needle is used to withdraw amniotic fluid
(Figure 15.37 (A)) containing cells genetically identical to those of the fetus. In
CVS, a catheter is inserted into the uterus and a small tissue sample of the fetal
chorion removed (Figure 15.37 (B)). In both cases, a variety of cytogenetic and
biochemical tests can then be performed on the cells and tissue to identify
any single gene disorders or chromosomal abnormalities.

People in whom a genetic defect has been detected will be advised to seek
genetic counseling, especially if they wish to have children. The advice they
are given is based on analyses of the risks that they may produce a child with a
genetic abnormality or that they themselves may develop a late onset genetic
disease. A broad range of information is required and genetic counselors
require training to provide this information with appropriate consideration.