Huntington's Disease: Two Families with Differing Clinical Features Show Linkage to the G8 Probe

• Published in: Science (American Association for the Advancement of Science) 1985-08, Vol.229 (4715), p.776-779
• Main Authors: Folstein, Susan E., Phillips, John A., Meyers, Deborah A., Chase, Gary A., Abbott, Margaret H., Franz, Mary L., Waber, Pamela G., Kazazian, Haig H., Conneally, P. Michael, Hobbs, Wendy, Tanzi, Rudolph, Faryniarz, Ann, Gibbons, Kerrin, Gusella, James
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Chromosomes, Human, 4-5; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; DNA probes; DNA Restriction Enzymes; DNA, Recombinant; Female; Fractions; Genetic Linkage; Genetic loci; Genotypes; Haplotypes; Humans; Huntington disease; Huntington Disease - genetics; Lod score; Male; Medical genetics; Medical sciences; Mothers; Neurology; Parents; Pedigree; Recombination, Genetic; Risk; Symptoms
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.2992086

To test the hypothesis that interfamily variability in Huntington's Disease (HD) is due to mutation at different loci, linkage analysis was undertaken in two large HD kindreds that differed in ethnicity, age-at-onset, and neurologic and psychiatric features. Both families showed linkage of the HD locus to the G8 probe. Several recombinants were documented in each family, and the best estimate of the recombination fraction for the two families was 6 percent with a 95 percent confidence interval of 0 to 12 percent. Although the data support the existence of a single HD locus, use of the G8 probe for presymptomatic testing in these kindreds would have resulted in a 12 percent error rate in genotype assignment at the HD locus.