Scientists announce two new genetic sites linked to familial ALS

July 23, 2003

Three independent groups of researchers have identified families with linkage to chromosome 16, providing strong evidence that another gene associated with familial ALS is close to being identified. There are four families linked to chromosome 16. The affected family members exhibit both upper and lower motor neuron involvement - classical ALS. In addition, one of the studies identified linkage in another family to chromosome 20.

These independent studies provide a powerful foundation from which to move in on the next ALS gene. This study has been greatly helped by the collaboration that has been of enormous value in consolidating the finding, according to Dr. Jackie de Belleroche, Imperial College London.

These findings are reported in three articles published in the August 2003 edition of the American Journal of Human Genetics. Among the research teams are currently ALSA-funded researchers Drs. Robert H. Brown, Massachusetts General Hospital, Jackie de Belleroche, Imperial College London, Charing Cross Hospital, and Christopher E. Shaw, King's College in London.

"The next step -- identification of the mutant gene -- will have an enormous impact on ALS research, similar to that of the SOD1 discovery in 1993," said Dr. Lucie Bruijn, science director and vice president, The ALS Association. "Because there is some overlap in linkage to a region on chromosome 16 in the four families, the region of special interest is reduced. That should expedite gene identification."

Several aggressive approaches are already underway to identify the specific gene. The ALS Association's Gene Identification Project is an accelerated approach. This $1.5 million collaborative study, launched last summer, is focused on chromosome 16. That project led by Drs. Robert Brown, Jackie de Belleroche, Guy Rouleau, Teepu Siddique, Eric Lander and Pieter de Jong applies techniques used in the Human Genome Project. In parallel, investigators are using the standard "candidate gene" approach, selecting genes in the area and sequencing them.

The ALS Association's interest in and support of ALS genetics studies dates back to the mid-1980s when other entities thought it too high risk. The payoff came in 1991 and 1993 with the discoveries of linkage of familial ALS to chromosome 21 and the mutant SOD1 gene respectively. Those discoveries have provided invaluable information about both familial and sporadic ALS, including models to study disease onset and progression as well as to test potential therapies.