Biology Reference
In-Depth Information
prohibition of racial and ethnic homogamy, there would appear to be no
rational justification for deploring the effect that assortative mating may
have had on the incidence of genetic deafness.
6. Summary
Interest in the genetics of deafness has a long history that predates the
rediscovery of Mendelism. Throughout most of the twentieth century,
geneticists argued about whether the genetics of deafness could best be
explained by dominant or recessive genes at one, two, three, or perhaps four
loci. By the 1970s, the concept of etiologic heterogeneity was well estab-
lished. However, it seemed inconceivable that it would ever be possible to
isolate and purify sufficient quantities of specific proteins from the cochlea
to actually identify the functions of the mutant genes for the various forms
of syndromic deafness that were being recognized. This volume is a testa-
ment to the revolutionary impact that molecular genetics has had on this
field since that time. A unique feature or the genetic epidemiology of deaf-
ness is the cultural variation that exists in the mating structure of the deaf
population. Now that the prevalence of specific genes in a population can
be measured, we are beginning to appreciate the profound effect that recent
changes in the mating structure have had on the frequency and distribution
of genes for deafness.
One of the major limitations of man as the object of genetic research is
the inability to
perform
experimental matings. As molecular testing for
specific forms of genetic deafness becomes available, the existence of
assortative mating among the deaf will ultimately provide an unparelleled
opportunity to search for interactions among non-allelic genes for deafness.
Since the conservation of phenotypes across species is far less complete
than the conservation of orthologous gene sequences, phenotypes that
result from interactions among genes are likely to be even less completely
conserved. Human model systems will therefore be essential to recognize
these effects. It should already be possible to ask, for example, if heterozy-
gosity for a connexin 26 mutation alters the expression of Waardenburg syn-
drome, Pendred's syndrome, the branchio-oto-renal syndrome, or Jervell
and Lange-Nielsen syndrome. The work of Morell et al. (1997) provides
hints on possible interactions between the WS 2 (
MITF
) and ocular
albinism (
TYR
) genes, and the observations of Balciuniene et al. (1998,
1999) suggest apparent interactions between genes at the
DFNA2
and the
alpha tectorin locus. Thus, specific digenic interactions may be an important
cause for variation in expressivity. However, as more deaf people get
cochlear implants, the opportunity to document the effects of gene inter-
actions on phenotype is likely to begin to disappear.
The knowledge that some forms of genetic deafness such as
connexin 26
and A1555G are much more common than all other types in some popula-
tions has also made it possible to contemplate radical “postgenomic” strate-
