Michigan Team Links Pair of Gene Mutations to Rare Caribbean Disorder
Researchers at the University of Michigan Medical School said they have identified two gene mutations that appear to be responsible for a rare neurological disorder.
Certain people who are natives on Grand Cayman Island in the Caribbean have the debilitating disorder, called Cayman ataxia. The syndrome, which is found nowhere else in the world, is characterized by poor muscle coordination, mental retardation, uncontrollable head and eye movements, and difficulty speaking or walking.
“Because these disorders are so rare, it is difficult to collect DNA samples from enough affected individuals in different families with the same disorder to pinpoint the mutations that cause them,” Margit Burmeister, a senior associate research scientist at the U-M Mental Health Research Institute, said. “Unless we can identify the mutated gene, it’s hard to develop a diagnostic test or a therapy to help people with the disease.”
Before the U-M study, which was a collaboration between the University of Michigan, the University of Miami, the University of Iowa, and the National Human Genome Center at Howard University, scientists knew that Cayman ataxia was caused by a recessive mutant gene that originated in one of the early residents of Grand Cayman Island and then was passed on to the generations by his or her descendants. In 1994, a team of scientists at the University of Iowa narrowed the search to one region on human chromosome 19, which included between 50 and 100 genes. However, the researchers were unable to locate the specific gene they believed was responsible for the disorder.
At around the same time, Burmeister, who is also an associate professor of psychiatry and of human genetics in the U-M Medical School, was studying a strain of mutant mice she called “jittery,” which displayed similar neurological symptoms that sometimes were fatal. Suspecting that the mice and its human Cayman ataxia counterpart shared a genetic component, Burmeister compared overlapping DNA sequences between the region on mouse chromosome 10, defined by the jittery mice, and the region on human chromosome 19, which is implicated in Cayman ataxia.
This research “narrowed the interval down to a much smaller region that contained just seven genes,” Burmeister said. In one of these genes, she explained, her team discovered two mutations — a recessive mutation that caused “lethal ataxia” in jittery mice, and a mutation that caused “milder symptoms” in a different strain of mice she called “hesitant.”
Analyzing DNA samples from Cayman Island residents with ataxia, and from relatives who did not have the disorder, Burmeister found the same two mutations in the same gene, which her she named ATCAY—Ataxia, Cayman type. Both mutations were present in every patient with Cayman ataxia in the study, according to Burmeister, and neither mutation was found in 1,000 control chromosomes from people of African, European, or Jamaican ancestry, she said.
She went on to say that one of the mutations in the ATCAY gene changes an amino acid while the other is a splice mutation that expresses a “non-functional, truncated” form of the protein caytaxin. Analyzing gene expression in tissue from mice in the study, the Burmeister’s team noticed that caytaxin protein “was present throughout the brain and in neurons, but nowhere else in the mouse’s body.”
Burmeister is working with structural biologists to determine what molecules will fit into the binding pocket of the caytaxin protein, according to the university. “If we can determine caytaxin’s function, that will tell us why these people have ataxia, which would be a major step toward finding ways to prevent or treat the disorder,” she said. Her research appeared in the Oct. 12 Nature Genetics online, and will run in the November issue of the journal.
US Senate Passes Genetic Anti-Discrimination Bill
The United States Senate this week unanimously passed legislation that would prohibit employers and health insurers from discriminating against individuals based on genetic data.
The bill would ban employers from making hiring, firing, and compensation decisions based on genetic information, and would make it illegal for insurers to set premiums or deny coverage based on these data. It would also ban businesses and insurers from requiring individuals to submit genetic information, except in certain limited cases.
The bill now faces the House of Representatives. The House Education and the Workforce Committee will hold hearings on the bill’s employment-related provisions, but House passage this year “seems unlikely,” according to the Wall Street Journal.
Groups representing health insurers and employers said that banning genetic discrimination is not needed because “the problem isn’t occurring ... ,” the paper said.