Huntington's disease (HD) results from genetically programmed
degeneration of nerve cells, called
neurons,
in certain areas
of the brain. This degeneration causes uncontrolled movements, loss
of intellectual faculties, and emotional disturbance. Specifically
affected are cells of the basal ganglia, structures deep within the
brain that have many important functions, including coordinating
movement. Within the basal ganglia, HD especially targets neurons
of the striatum, particularly those in the caudate nuclei and the
pallidum. Also affected is the brain's outer surface, or cortex,
which controls thought, perception, and memory.
HD is found in every country of the world. It is a familial
disease, passed from parent to child through a mutation or
misspelling in the normal gene. A single abnormal gene, the basic
biological unit of heredity, produces HD.
Genetic structure
Genes are composed of
deoxyribonucleic acid (DNA)
, a
molecule shaped like a spiral ladder. Each rung of this ladder is
composed of two paired chemicals called bases. There are four types
of bases-
adenine
,
thymine
,
cytosine
, and
guanine
&151;each abbreviated by the first letter of its
name: A, T, C, and G. Certain bases always "pair" together, and
different combinations of base pairs join to form coded messages. A
gene is a long string of this DNA in various combinations of A, T,
C, and G. These unique combinations determine the gene's function,
much like letters join together to form words. Each person has
about 100,000 genes-three billion base pairs of DNA or bits of
information repeated in the nuclei of human cells-which determine
individual characteristics or traits.
Genes are arranged in precise locations along 23 rod-like pairs
of
chromosomes
. One chromosome from each pair comes from an
individual's mother, the other from the father. Each half of a
chromosome pair is similar to the other, except for one pair, which
determines the sex of the individual. This pair has two X
chromosomes in females and one X and one Y chromosome in males. The
gene that produces HD lies on chromosome 4, one of the 22
non-sex-linked, or "autosomal," pairs of chromosomes, placing men
and women at equal risk of acquiring the disease.
The impact of a gene depends partly on whether it is dominant or
recessive. If a gene is
dominant
, then only one of the
paired chromosomes is required to produce its called-for effect. If
the gene is
recessive
, both parents must provide chromosomal
copies for the trait to be present. HD is called an autosomal
dominant disorder because only one copy of the defective gene,
inherited from one parent, is necessary to produce the disease.
Genetic defect is responsible
The genetic defect responsible for HD is a small sequence of DNA
on chromosome 4 in which several base pairs are repeated many, many
times. The normal gene has three DNA bases, composed of the
sequence CAG. In people with HD, the sequence abnormally repeats
itself dozens of times. Over time-and with each successive
generation--the number of CAG repeats may expand further.
Each parent has two copies of every chromosome but gives only
one copy to each child. Each child of an HD parent has a 50-50
chance of inheriting the HD gene. If a child does not inherit the
HD gene, he or she will not develop the disease and cannot pass it
to subsequent generations. A person who inherits the HD gene, and
survives long enough, will sooner or later develop the disease. In
some families, all the children may inherit the HD gene; in others,
none do. Whether or not one child inherits the gene has no bearing
on whether others will or will not share the same fate.
A small number of cases of HD are sporadic. They occur even
though there is no family history of the disorder. These cases are
thought to be caused by a new genetic mutation-an alteration in the
gene that occurs during sperm development and that brings the
number of CAG repeats into the range that causes disease.
