Gene tracking

Once a disease gene has been located using linkage analysis,
DNA markers can be used to track the disease gene through
families to predict the genetic state of individuals at risk. Prior
to identifying specific gene mutations, this can provide
information about carrier risk and enable prenatal diagnosis in
certain situations. Before gene tracking can be used to provide
a predictive test, family members known to be affected or
unaffected must be tested to find an informative DNA marker
within the family and to identify which allele is segregating with
the disease gene in that particular kindred. Because
recombination occurs between homologous chromosomes at
meiosis, a DNA marker that is not very close to a gene on a
particular chromosome will sometimes be inherited
independently of the gene. The closer the marker is to a gene,
the less likely it is that recombination will occur. In practice,
markers that have shown less than 5% recombination with a
disease gene have been useful in detecting carriers and in
prenatal diagnosis, although there is always a margin of error
with this type of test and results are quoted as a probability of
carrying the gene and not as a definitive result. Linkage studies
using intragenic markers provide much more accurate
prediction of genetic state, but this approach is only used now
when mutation analysis is not possible, as in some cases of
Duchenne muscular dystrophy, Marfan syndrome and
neurofibromatosis type 1.