|
|
|
Indirect testing for genetic markers in a family that has a number of patients -
when there are a number of genes that can each cause the disease - not all genes
having been located / identified / mapped - autosomal dominant diseases
|
|
This is not a direct test, but a comparative one, which is called linkage analysis.
In genetic linkage studies, alleles of each of the genes being tested (an allele
is one member of the pair of genes at a given disease locus) are compared between
the patients and the healthy family members. The allele that is present only in
the patients but in none of the healthy family members - i.e. the "shared allele"
of these patients - is the one in which the mutation responsible for the disease
is located. If the -shared allele- is found, it will be possible to test other family
members without identifying the mutation itself, and prenatal testing by amniocentesis or chorionic villus sampling can be carried
out. This is done by looking for the "shared allele" in the
DNA of the affected individuals in the family.
|
|
|
The problem here is that there is genetic heterogeneity, and the gene responsible
for the disease in the family being investigated must be identified out of the several
genes that can cause the disease.
Because not all of the genes have been identified, the test cannot be completed
- it takes a long time and will not be completely reliable.
However, in very large families with a large number of affected individuals (at
least 7), an attempt can be made.
This can be done by performing a separate comparative test for the locus of each
of the possible genes.
|
|
Only in the locus containing the gene responsible for the disease will there be
complete correlation between the genotype and the phenotype - in other words, the
-shared allele- will be found in all the patients, but in none of the healthy relatives.
In the other loci, complete genotype-phenotype correlation will not be found.
The test requires comparison of a number of affected and healthy members of the
same family. The test is only reliable if DNA from several affected individuals
in the family is already available, or if it can be obtained from a blood (or other)
sample. The cooperation of the family members is required - they must be examined
by a physician in order to ascertain whether they have signs of the disease, and
must agree to give a blood sample. Sometimes the test is pure research. The more
candidate genes there are, the more complex and difficult it is to perform the test.
If none of the known genes is responsible for the disease in the family being investigated,
a different gene must be sought.
|
|
|