Biology Reference
In-Depth Information
genes known to cause either syndromic or nonsyndromic hearing loss.
For example, the genes for BOR (
EYA1
), DFNB3 (
GJB2
), and DFNA9
(
COCH
) are among the cochlear ESTs. Interestingly, genes for other
hearing disorders, for example human
diaphanous
(DFNA1) and
POU4F3
(DFNA15), which are known to be expressed in fetal cochlea, were not
among the cochlear ESTs; this is because the library was not exhaustively
sequenced, and less abundant messages were thus less likely to be detected.
Sequencing of additional cochlear clones would provide a more com-
plete survey of all the genes expressed in this tissue, and such an effort is
currently underway.
3.1.2 Cochlear-Specific ESTs
Sequence matches were not detected in GenBank for 540 cochlear ESTs.
These clones may represent genes that are uniquely expressed in the inner
ear. It is perhaps not surprising that an organ as complex as the cochlea
would express exclusively a large number of genes. Further investigations
using tissue hybridization studies and cell-type-specific cDNA libraries are
required to determine whether these genes are widely expressed in cochlea,
or confined to a specific cell type.
3.1.3 Map Locations of Cochlear ESTs Provide Candidate Genes
for Hearing Disorders
Many genes for nonsyndromic deafness are yet to be identified. Because of
small pedigree sizes, geographically isolated populations and the difficulty
in grouping kindreds because of genetic heterogeneity, a precise location of
the gene cannot be determined by linkage analysis (Mueller, Van Camp,
and Lench, Chapter 4). The task of identifying the pathogenetic sequence
in a chromosomal segment can be quite daunting. Clearly, positional-
candidate genes and ESTs within the region of interest are the first to be
investigated, with a high priority being given to those that are known to be
expressed in the cochlea.
Several hundred of the cochlear ESTs have been mapped. Of these, 57
map to the genetic intervals of 22 different syndromic and nonsyndromic
hearing disorders (Skvorak et al. 1999), making them immediate positional
candidates for these disorders (Fig. 5.11). This approach successfully iden-
tified
COCH
as the defective gene in DFNA9 deafness (Robertson et al.
1998).
3.2 Other Cochlear Libraries
Several cochlear libraries have been constructed from various rodent or
avian cochlear tissues. Creating libraries from model organisms has two
advantages. First, because much research in the molecular biology of
hearing is conducted in model organisms such as rodents and birds, cDNA
