A slew of genes linked to brain disorders were among the highlights of another rich year in medical genetics:
Epilepsy and mental retardation: Usually, mutant genes on the X chromosome affect only men, because they, unlike women, don’t carry a second copy that can compensate. This past year researchers identified a mutant gene on the X that causes epilepsy and retardation only in women. Male carriers of the mutation are somehow spared its bad effects, but they pass on the disorder to their daughters.
Parkinson’s Disease: A mutant gene on chromosome 4 may give rise to some early-onset cases. The gene codes for the brain protein alpha-synuclein; a mutation is thought to produce misfolded proteins, which accumulate in the brain and may kill neurons that make dopamine. Loss of that neurotransmitter leads to tremors and muscle rigidity.
Boxer brain: Boxers with chronic brain injury—which has symptoms similar to Alzheimer’s and Parkinson’s diseases—are far more likely to carry a gene on chromosome 19 that has also been linked to Alzheimer’s. Repeated blows to the head may trigger the deposit of beta-amyloid, a brain protein associated with Alzheimer’s, and carriers of the gene may be less able to repair such injuries.
Breast cancer: Exposure to estrogen is a known risk factor for breast cancer. This past year researchers found that women with a variant form of a gene involved in estrogen production have over double the risk of developing advanced breast cancer—perhaps because they make more estrogen. The gene variant, on chromosome 10, may contribute to about 30 percent of all cases of the disease.
Familial Mediterranean fever: This disorder, which causes arthritis as well as fever, is prevalent among North African Jews, Armenians, Turks, and Arabs. This year researchers not only pinpointed the fmf gene on chromosome 16; they also traced the origin of two disease-inducing mutations back to two people who lived in the Middle East as long as 40,000 years ago. The gene codes for a protein in white blood cells; when mutated, it induces bouts of fever.
Fetal alcohol syndrome: High doses of alcohol early in pregnancy switch off a gene that controls the development of the brain, heart, limbs, and skull—of mouse embryos, anyway. But since the same gene is found in humans on chromosome 5, the researchers who made the discovery think it may account for the malformations characteristic of fetal alcohol syndrome.
Heroin addiction: Some cases have been linked to a gene on chromosome 11 that codes for a dopamine receptor on brain cells. An abnormally long form of the gene has turned up not only in drug addicts but in other people who exhibit novelty-seeking behavior.
Glaucoma: A mutant gene on chromosome 1 leads to juvenile-onset cases and some adult cases of this disease, which causes vision loss. The defective protein it makes may gum up the meshlike filter that drains water from the eyeball, allowing fluid to build up and damage the optic nerve. The discovery will permit doctors to look for the mutation in relatives of people with glaucoma and to treat them if necessary before they, too, go blind.
Obsessive-compulsive disorder: Between 1 and 3 percent of the population feel pathologically compelled to repeat certain behaviors, such as washing their hands. This year a gene on chromosome 22 was linked to some cases of the disorder in men. The gene codes for an enzyme that breaks down dopamine and another neurotransmitter, norepinephrine, after they have carried a signal across the gap between brain cells. Men with ocd are more likely to have a less active version of the enzyme—and thus perhaps an excess of the neurotransmitters.
