Biology Reference
In-Depth Information
5.2 Pseudodominance
Knowledge of the high frequency of
Cx26
deafness provides a satisfying
explanation for two anomalies in Rose's analysis of the Fay data set (Table
4.2). In the proband sibships, which included data on the phenotypes of
parents and siblings obtained by selection through affected probands, Rose
estimated that the proportion of dominant phenotypes among the genetic
cases was 12%. In contrast, the proband matings that were ascertained by
selection through affected parents yielded an estimate of 16.9% for the fre-
quency of segregating matings, which were assumed to result primarily from
dominant transmission of the deafness phenotype. Furthermore, the esti-
mated segregation ratio for the dominant cases in the proband sibships
was 0.26,while the ratio in the segregating proband matings was 0.325. In view
of the low penetrance for deafness in dominant phenotypes such as Waar-
denburg syndrome, the observation of a low segregation ratio for dominant
deafness was not surprising. However, there would seem to be no good expla-
nation why the penetrance should vary with the mating type of the parents. It
now seems likely that the increased frequency and penetrance of the deafness
phenotype in the segregating DxD matings reflects the presence of fully pen-
etrant pseudodominant
Cx26
phenotypes in about 19% of the segregating
DxD matings. Over time, the frequency of pseudodominant transmission
would be expected to increase in an assortatively mating population as the
frequency of gametes carrying multiple genes for deafness increases.
Evolutionary biologists now agree that the acquisition of syntactic speech
50,000 years ago resulted in an explosive acceleration in the evolution of
the human brain.
The recent cloning of a major gene that is of importance for the devel-
opment of speech (Lai et al. 2001), suggests that this process may have been
initiated by the mutation and subsequent fixation in the population of a rel-
atively small number of genes. The rapid changes that have occurred in the
frequency of
Cx26
deafness following the introduction of sign language
suggest that the combination of linguistic homogamy and improved genetic
fitness may also have contributed to the rapid evolution of speech. This
mechanism will also amplify the frequency of genes that interact with the
primary locus and could therefore have contributed to selection for genes
that influence other mental traits that depend upon speech and language
for their expression. In this regard, it is of great interest that epistatic inter-
actions with mutations at separate loci are now being recognized to be an
important cause for “digenic” deafness in deaf subjects who carry only a
single pathologic mutation at the
Cx26
locus (Lerer et al. 2001).
5.3 Potential Effects of Marital Selection for Cx26
Some deaf couples do not regard hearing loss as a handicap and would
prefer to have deaf children. Most express no strong preference, while many
would clearly prefer hearing children (Middleton et al. 1998). Since testing
