Two articles in scientific journals this week reported findingsthat may have pinpointed the gene responsible forHuntington's disease (HD).
Researchers from the University of British Colombia andToronto's Hospital for Sick Children report in today's issue ofNature that they have identified a "strong candidate" gene forHD.
And the Huntington's Disease Collaborative Research Group(HDCRG) reports in Friday's issue of the journal Cell that it haslocated the HD gene.
Researchers the world over have spent the better part of 10years trying to pinpoint the exact location of the gene thatcauses this neuropsychiatric disorder, a disease often describedas relentless in its progression toward a certain death. About30,000 Americans suffer from the disease, and another150,000 are at risk.
Michael Hayden and his Canadian colleagues concentrated onthe 2.2 megabase interval of DNA on the tip of chromosome 4,the known address of the HD gene, which now contains animpressive number of mutational markers on the genetic map.
Hayden and his associates analyzed 250 HD families forrecombinational events between some of those markers(including D4S180, D4S95 and D4S182) to bring them closer totheir target. They then used a direct complementary DNA(cDNA) selection strategy to identify seven transcriptional unitswithin that candidate-gene region.
The researchers found a common transposable element (orjumping gene), the Alu insert, in genomic DNA from twoindividuals with the disease (but not in 1,000 controlchromosomes). And this Alu happens to occur in the HDcandidate region, near one end of the already-identified genethat codes for alpha-adducin.
But Hayden and his colleagues found that another gene --previously unknown -- in the region codes for a 12-kilobasetranscript that maps close to the Alu insertion site. And it's that12-kilobase transcript that "should be regarded as a strongcandidate for the HD gene," they concluded.
The HD Collaborative Research Group, led by James Gusella ofMassachusetts General Hospital in Boston, has identified a genemapping to this area (the 500 kb segment between markersD4S180 and D4S182) that contains a three-base-pair-repeatsequence (CAG) that is "expanded and unstable" on HDchromosomes. The researchers found the CAG repeat (whichvaries in the actual number of copies) on chromosomes from all75 HD families included in their analysis.
"The CAG repeat appears to be located within the codingsequence of a predicted 348 kd protein (they called the geneIT15) that is widely expressed but unrelated to any knowngene," the authors stated. The data suggest that "IT15 encodesthe HD gene."
Have the two groups of researchers hit the same bullseye? "Wedon't know yet," commented Johanna Rommens, a senior authoron the Nature paper. She explained that both groups haveidentified a genetic change associated with the disease inHuntington's families, but "theirs looks a little different thanours."
Rommens told BioWorld that it's possible that the HD genecould be disrupted in more than one way, or that "what wefound is an absolute association and not a cause." There's moreanalysis to come to answer such questions, she added.
-- Jennifer Van Brunt Senior Editor
(c) 1997 American Health Consultants. All rights reserved.