Biology Reference
In-Depth Information
providing a total of 46 chromosomes (22 autosomal pairs plus XX or XY)
in the nucleus of a cell. If both parents transmit an X chromosome, the off-
spring is female (XX); if the father transmits a Y chromosome, then the off-
spring is male (XY). The distribution of family members with hearing loss
may be consistent with autosomal or X-linked inheritance, which may be
further categorized as dominant or recessive. The symbol assigned to a non-
syndromic form of hearing loss reflects the mode of inheritance. DFNA*
and DFNB* (*the asterisk represents a number that is assigned when the
gene for the hearing loss is localized to a chromosome) indicate autosomal
dominant and autosomal recessive, respectively, while DFN* means X-
linked. The number does not reflect the chromosomal location;
DFNB7
,
for example, simply means that the gene for this form of autosomal reces-
sive hearing loss was the seventh to be localized (the
DFNB7
gene is on
chromosome 9). If the pattern of inheritance is consistent with maternal
transmission, the location of the gene may be the mitochondrial genome
(Fischel-Ghodsian, Chapter 7). For hearing loss, there is general agreement
that the pattern of inheritance is autosomal recessive in about 77% of cases,
autosomal dominant in about 22%, and X-linked or mitochondrial in the
remainder (Gorlin et al. 1995).
An individual has pairs of chromosomes and, therefore, pairs of genes
and pairs of genetic markers (fragments of DNA that have unique chro-
mosomal locations). The chromosomal location of a gene or genetic marker
is its locus. The different forms of genes and genetic markers are called
alleles; thus, at each locus an individual has two alleles, and this pair of
alleles is the genotype. The genotype of the individual is homozygous if the
two alleles are the same, and heterozygous if they are different.
1.2.1 Autosomal Dominant Inheritance
The pattern of inheritance is probably autosomal dominant if individuals
in each generation are affected; both males and females are equally likely
to be affected. Affected individuals are usually heterozygotes with one
normal and one deleterious copy of the gene for the disorder, and each
offspring of an affected individual has a 50% chance of inheriting the
deleterious allele. However, knowing the genotype may not be adequate in
predicting the phenotype. There may be variable expression among affected
individuals, and some who must have the deleterious allele (because, for
example, they have an affected parent and an affected child) may show no
phenotypic signs.
Penetrance is defined as the probability of expressing features of the
phenotype given the presence of a particular genotype. For a dominant
disorder, if 70% of individuals who have the deleterious allele show some
phenotypic expression of the disorder, then the penetrance value is 0.7. Pen-
etrance may also be age dependent, such as with adult-onset hearing loss.
In this case, the probability that a person who has the deleterious allele will
