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Why do genes cause
genetic diseases?
Tay-Sachs disease is a parent’s nightmare. Your
beautiful, bouncing, healthy, happy baby gradually
can no longer hold his head up, see, move, or eat.
His nervous system degenerates, and he will die by
the age of five. There is nothing you can do.
The tragedy of Tay-Sachs begins when a child receives a
copy of a faulty gene from each parent. Each of these parents
carries one faulty copy, but they each have a normal version
that keeps them healthy. Each of their children then has a
25% chance of inheriting the deadly double dose, according to
the typical recessive inheritance pattern. Also, each child has
a 50% chance of inheriting one faulty gene and thus becoming
a carrier for a future generation.
Why would there be such a disease?
Genes don’t exist to cause
disease. They perform functions in
the body. If they become mutated,
they sometimes can’t perform their
normal function. That’s the case with Tay-Sachs. Normally,
the healthy Tay-Sachs gene produces part of an enzyme.
(An enzyme is a protein that reacts with and reorganizes
other molecules.) This particular enzyme, called HexA
Healthy Neuron
Lysosome (waste disposal site)
Neuron Affected by Tay-Sachs
Lipids (GM2 ganglioside)
Bulging Lysosome
(lipid waste accumulation)
6 Cracking the Code of Life
In healthy neurons, lysosomes
contain enzymes that break
down wastes from the cell. In
Tay-Sachs, one of those
enzymes (HexA) is inactive, so
waste lipids build up and
eventually destroy the neuron.
a four
is
(b-hexosaminidase A), breaks down
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glass, aluminum, or paper. In the
a baby girl born with a random mutation. If she survives,
same way, the lysosome has specialeach of her children could inherit a copy of that mutation.
ized disposal enzymes assigned to
The more children, the more potential copies. If the children
different waste molecules. In this case, HexA
belong to a group that is isolated or marries only within itself for
breaks down a lipid (fatty substance) called GM2 ganglioside.
religious or social reasons, the mutation will become common in
This lipid is used in the cells of the brain and nervous system, so
that population. Soon carriers of the mutation will have children
that’s where HexA is needed.
with double copies of it … and a recessive disease is born.
In Tay-Sachs, the gene for the HexA enzyme is
Scientists call this pattern the “founder effect” because only a few
mutated, so the enzyme can’t degrade the
people start (“found”) the disease in their descendents. (We’ll see
lipid. It’s as if the worker assigned to
another founder effect in the article on Iceland.)
glass stops working, so glass builds up
This pattern explains why Tay-Sachs is common
in the warehouse. The lipids build up
among Ashkenazi Jews, who make up 80% of modern
about it
in the lysosome, and the bulging
Jews. (One in twenty-seven Ashkenazi Jews carry one
lysosomes damage the cell. The nerve
copy of the Tay-Sachs gene.) Ashkenazi Jews moved
cells degenerate and die.
from Russia to Europe to escape persecution in the
Would you use such a
1600s. In Europe, they were confined to crowded urban
matchmaker service?
ghettos for centuries. They formed a tight-knit group
Would you still marry your
and didn’t marry outsiders, so there was a greater chance
true love if you both
What Should
that two people with a Tay-Sachs gene would marry. In
shared a Tay-Sachs gene?
that way, the Tay-Sachs gene became concentrated.
Be Done?
Furthermore, tuberculosis (TB), an extremely
Would other less-deadly
Genetic tests have really reduced the
infectious
and deadly disease, ran through the ghetto
genes affect your decision
number of Tay-Sachs babies born in
like
a
wildfire.
It reduced the population and further
to marry?
high-risk populations. If both you and
concentrated the Tay-Sachs gene. Some scientists even
wonder whether the carriers (with just one Tay-Sachs
your spouse are Tay-Sachs carriers,
gene)
were
somehow protected from TB. If so, people with the
you can choose to not have children or to have prenatal
normal gene would die while the carriers survived, making the
testing for the fetus. But what then? Should prenatal
Tay-Sachs gene even more common among descendents.
testing be required? Tay-Sachs also exists in the general
population, even though it is rare. Should genetic
What can be done?
testing be for just high-risk groups or for everybody?
For now, there is nothing that parents can do for a baby with
Tay-Sachs. Doctors cannot give babies a dose of the missing
Orthodox Jews don’t believe in prenatal testing, birth
enzyme because the brain, which is the organ most damaged by
control, or abortion. Still, they want to spare their
the disease, has a protective barrier that would keep the enzymes
community from the tragedy of
out. But genomic research may someday help. Scientists might
Tay-Sachs. They created a
modify a specific bacterium that infects the brains. They might
voluntary program of anonydisable it so it can’t cause disease and have it carry the gene for
mously registering people’s
HexA to the brain. Or they might transplant neurons with the
healthy gene in the brain to replace the damaged cells. They
DNA with a “matchmaker”
might devise drugs that prevent brain cells from making so many
who stores information about
lipids, so the enzyme has less work to do.
whether they carry the recessive disease gene. When
Career Connection: Disease Researcher:
they’re ready to marry, they
Use genomics to understand how diseases like diabetes
can ask the matchmaker if they
and asthma develop and how to control them.
and their “intended” share the
Tay-Sachs genes.
Think
!
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