PGD - Linked Markers
Linked Markers
Linked Markers are genes that are so closely associated on the chromosome that they are inherited together in 80% or more of cases. Linked Markers are used to improve the accuracy of the DNA tests.
Technique:
Different expressions of a single gene are known as alleles. A large library of genetic probes
has been created that can specifically identify different alleles at specific gene sites that
cause many genetic disorders. In some conditions, there are many different possible mutations of
the gene, and specific probes for each patient are created.
With recessive traits, like cystic fibrosis,
for a couple that has had a previous child with the disorder, each parent possesses a normal and an
abnormal allele. When these two people reproduce, on average 50% of their embryos will carry one
copy of the abnormal allele and 25% will carry two copies of the abnormal allele and will be affected
by the disease. For dominant traits, one copy of the abnormal allele is sufficient to cause the disease.
In most cases, people who have one abnormal dominant allele have the condition in question. Therefore,
each of their offspring has a 50% chance to inherit the gene, and thus the disease.
In theory, blastomere biopsies are superior to polar body biopsies, because they allow identification
of both maternal and paternal genes. This allows differentiation of normal, carrier, and disease states.
This approach uses the technology of polymerase chain reactions (PCR). DNA strands are cut into smaller
pieces by enzymes, and millions of copies of the DNA are produced by the PCR. The strands of DNA are
allowed to come back together, and abnormal genes cause the strands to align differently, thus allowing
the identification of the abnormal gene.
Unfortunately, because of a technical problem, known as allele
dropout (ADO), an abnormal allele can be hidden or not detectable by the testing, so that an embryo with a
genetic abnormality could appear to be unaffected. To minimize the interference of ADO, if both parents
have the same gene mutation, polar body biopsy is done first. Depending on how many copies of the abnormal
allele are present in the polar bodies, we can determine whether the egg carries the normal allele or the
abnormal allele. All eggs that carry the abnormal allele are eliminated. Because polar body biopsy only
analyzes the maternal contribution of the DNA, this technique cannot determine whether the resulting
embryo would be normal or a carrier of the disease. Therefore, blastomere biopsy may need to be
performed as a second step. To further reduce the problems associated with ADO, and increase the accuracy
of DNA tests, linked markers are also utilized. Linked markers are segments of DNA that lie very close
to the gene being studied. By testing the linked markers, as well as the gene in question, we can confirm
the results of the genetic testing and determine whether ADO has occurred.
Treatment Value:
There is a high level of association of linked marker with a determining gene. Depending
on whether the linked marker is associated with a dominant-determinant or a recessive-determinant gene,
the degree of predictability of the linked marker for susceptibility will vary a little.
In summary, by using the Linked Markers technique in combinations with other techniques, we are able to improve our
accuracy, and reduce the risk of genetic disorders.
Next Step:
To find out more, please Contact us.