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A DNA segment encoding two genes very tightly linked to Huntington's disease
T C Gilliam1, M Bucan, M E MacDonald
1Neurogenetics Laboratory, Massachusetts General Hospital, Boston.
Science (New York, N.Y.)
|November 13, 1987
Summary
Researchers identified D4S43, a DNA marker tightly linked to Huntington's disease (HD). This discovery advances the potential for presymptomatic diagnosis and gene localization for this neurodegenerative disorder.
Area of Science:
- Genetics
- Neurodegenerative Disorders
- Molecular Biology
Background:
- Huntington's disease (HD) is a late-onset neurodegenerative disorder.
- Previous DNA marker D4S10 offered limited presymptomatic diagnosis for HD.
- Progress in understanding HD genetics was hindered by a lack of closely linked DNA markers.
Purpose of the Study:
- To identify novel DNA markers with extremely tight linkage to the Huntington's disease gene.
- To refine the chromosomal location of the HD defect.
- To identify candidate genes for Huntington's disease.
Main Methods:
- Screening for anonymous DNA loci on chromosome 4.
- Genetic linkage analysis in three extended Huntington's disease kindreds.
- Expansion of the D4S43 locus and identification of restriction fragment length polymorphisms (RFLPs) and coding segments.
Main Results:
- A novel DNA locus, D4S43, was identified with extremely tight linkage to HD.
- D4S43 is located in the distal region of chromosome 4 short arm, within 0 to 1.5 centimorgans of the HD gene.
- Eight RFLPs and at least two coding segments were identified within the expanded D4S43 region, with no observed recombination with HD.
Conclusions:
- The D4S43 locus represents a significant advancement for presymptomatic diagnosis and gene mapping of Huntington's disease.
- Candidate genes within the D4S43 region are strong contenders for the site of the HD defect.
- Further investigation is needed to confirm the causal mutations within the identified candidate genes.