Biology Reference
In-Depth Information
ogy to known genes and proteins (Altschul et al. 1990; Altschul et al. 1994).
In addition, computer programs such as Gene Recognition Analysis
and Internet Link (GRAIL) (http://www.ncbi.nlm.nih.gov/genemap) and
GENSCAN can be used to interrogate sequence data for the presence of
features that suggest genes, such as splice-site consensus sequences.
9.6.1 In Silico Cloning
The burgeoning field of bioinformatics is a rapidly growing discipline as a
consequence of the large amount of DNA sequence information that is
available. It is now possible to clone genes from sequence data analysis
alone; this has been called “in silico cloning.” Two genes for inherited
hearing impairment, the gene for Pendred's syndrome (Everett et al. 1997)
and the
DFNA5
gene (Van Laer et al. 1998), have been identified this way.
This approach will almost certainly result in the identification of an increas-
ingly greater proportion of the genes for inherited hearing impairment with
the availability of the EST and human genome DNA sequence data.
10. Summary
Over the past six years, linkage studies of families with autosomal domi-
nant, autosomal recessive and X-linked syndromic and nonsyndromic sen-
sorineural hearing impairment have resulted in mapping of 30 autosomal
dominant, 28 autosomal recessive and 5 X-linked loci for nonsyndromic
hearing impairment. Physical mapping and the use of a variety of cloning
approaches over the same time period have led to the identification of 18
of these genes. Further progress in the mapping and cloning of genes for
inherited hearing impairment can only accelerate in the future.
There is an urgent need to document in detail the phenotypic features in
persons with inherited hearing impairment, and to correlate them with the
genotypic findings, both the particular gene involved and the specific muta-
tion responsible. In addition to the audiological findings (severity of hearing
impairment, age of onset, progression, audiological configuration, etc.), the
description of the phenotype should include documentation of the presence
or absence of associated vestibular abnormalities, and/or neuroradiological
findings in the inner ear. By this means, the results of the research findings
will rapidly translate into the development of directed and appropriate
mutation testing, not only for individuals with or at risk for inherited
hearing impairment, but also for the most common scenario, namely the
sporadic child with nonsyndromic sensorineural hearing impairment, for
whom limited diagnostic tests are available.
The identification of the normal function of the products of the genes
responsible for inherited hearing impairment will help us understand
how mutations in them result in hearing impairment, as well as identifying
