Biology Reference
In-Depth Information
Genes and Mutations in Hearing
Impairment
KAREN B. AVRAHAM and TAMA HASSON
1. Introduction
In the last five years, scientists have made great advances in deciphering
the genetic basis of hearing impairment. A fundamental knowledge of
the structure of chromosomes and genes is required to appreciate the
events leading to mutations causing hearing loss. This chapter covers the
organization of chromosomes and genes, discusses the flow of information
from DNA to RNA to protein, and delineates how different types of muta-
tions lead to abnormal gene expression or gene products. The mutations
described are a representative sampling, not an exhaustive list, of mutations
in genes that lead to hearing loss. Many more examples are described in
the literature and the list is growing monthly. The emphasis will be on muta-
tions associated with human deafness (Griffith and Friedman, Chapter 6),
although examples of mouse mutations will also be mentioned, because of
the relevance of mouse models to human hearing loss (Steel, Chapter 8).
For additional background information regarding the structure of chro-
mosomes and genes, the reader is referred to Lodish et al. (1995), Klug and
Cummings (1997), and Lewis (1999).
2. Chromosome Structure
Eukaryotic cells contain large linear chromosomes, which carry the genetic
material in the form of genes composed of DNA (Fig. 2.1). Most somatic
cells contain two copies of each chromosome derived from the germ cells
of each parent. Exceptions include: the haploid gametes, the sperm and egg
cells, which contain only one set of chromosomes; the platelets and red
blood cells, which lack a nucleus; and polyploid cells, such as liver regener-
ating cells and bone marrow megakaryocytes.
Chromosome size and number vary with species. In general, there is a
correlation between the complexity of the species and the genome size. The
yeast genome size is 14 megabases (Mb), whereas the genomes of the mouse
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