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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 How do recessive ow achs S y see h a o T t other molecules. It works inside diseases start? n i 5 age 1 ation p t e u n h the cell’s waste disposal center, Mutations happen all the o t m y t mmon he activit affec o n c a which is called the lysosome. time by chance, but only t c os es yt The m sertion. Tr and chang Imagine a recycling center some survive from generation in s, where different workers are to generation – depending on letter s, deletion n o i . assigned specific jobs for recycling environmental or social condit e r n inse f a ge o ” different types of waste, such as tions. A genetic disease starts with one person. Imagine g n i “mean 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 ! Your World 7