Indirect testing for genetic markers in a family that has one or several patients
- when there are a number of different genes that can each cause the disease - the
gene, or most of the genes not having been located / identified / mapped - multifactorial
Ths 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.
Because the location of the disease-causing gene, or most of the genes, has yet
to be identified, the test cannot be completed. There are a number of genes that
can each cause the disease, and in different families, different genes in different
combinations will result in the disease-s being expressed, so the problem is even
more severe. In addition, the inheritance pattern of the disease and the specific
contribution of each gene to its expression have not yet been adequately elucidated.
Another factor that compounds the issue is what effect if any the environment has.
However, in very large families with a large number of patients an attempt can be
made to locate the genes.
This can be done by performing a comparative test for each of the regions in the
genome (or candidate areas).
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 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. The more candidate genes there are the more complex and difficult
it is to perform the test, as a new gene must in fact be identified.