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Two neurodegenerative diseases linked to location
on chromosome 9
Researchers used genome scans to find region; gene is still at large
  
By
Edward R. Winstead


Researchers have located a region of chromosome 9 that may contain a gene involved in two neurodegenerative diseases that arise concurrently. An inherited form of amyotrophic lateral sclerosis, or ALS, sometimes occurs along with dementia, and individuals with this disease appear to have a defective gene in common on chromosome 9. The target region is roughly one-tenth of the chromosome, and the gene has not been found.

Individuals with ALS progressively lose the ability to move until they are paralyzed. But most cases of ALS, also known as Lou Gehrig's disease, involve the deterioration of only motor neurons. This selectivity has long been a puzzle: Why is only one class of nerve cells affected? Researchers may be able to investigate the phenomenon in the families that have members with both ALS and dementia.

"There may be something on chromosome 9 that is killing motor neurons and neurons in the frontal temporal lobes," says Betsy Hosler, of Massachusetts General Hospital and Harvard University. "Once we identify what that thing is, we may figure out why it's specialized to a particular class of neurons." Hosler led the chromosome 9 study, which has recently appeared in The Journal of the American Medical Association.

Hosler and her colleagues screened the genomes of 16 ALS families in the Boston area. They reviewed the medical records and discovered that in each family several patients developed motor neuron disease concurrently with progressive dementia. The families are among hundreds that were recruited in the early and mid-1980s for ALS studies. Researchers at four centers (Harvard, Duke, Vanderbilt, and Northwestern universities) have been conducting genome scans of this population.

The importance of the chromosome 9 region was hypothesized following an analysis of data on the 16 Boston families. The researchers tested the hypothesis using data from 4 ALS families in the Chicago area, 3 of which had members with concurrent dementia. The 3 families with dementia showed linkage to location on chromosome 9, but the family without dementia did not. "We were surprised to see that the linkage was so distinct," says Hosler.

Only about 10 percent of the ALS cases are inherited. Of these, 25 percent are due to defects in a gene on chromosome 21 that was identified in 1993. ALS researchers have been using the genome scans to find genes involved in the majority of inherited cases, and several other chromosomal regions of interest have been identified.

But those regions may not be relevant, and Hosler points out that the pool of ALS families that are likely to be informative is shrinking. Finding new, large families with affected and unaffected members is difficult. "Unless a family is very large, we don't have much statistical power to determine whether a region of interest occurs by chance or is real," she says.

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Hosler, B.A. et al. Linkage of familial amyotrophic lateral sclerosis with frontotemporal dementia to chromosome 9q21-q22. JAMA 284, 1664-1669 (October 4, 2000).
 

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