A Huntington disease-like neurodegenerative disorder maps to chromosome 20p.
Huntington disease (HD) is an autosomal dominant neurodegenerative disorder characterized by motor disturbance, cognitive loss, and psychiatric manifestations. The disease is associated with a CAG trinucleotide-repeat expansion in the Huntington gene (IT15) on chromosome 4p16.3. One family with a history of HD was referred to us initially for predictive testing using linkage analysis. However, the chromosome 4p region was completely excluded by polymorphic markers, and later no CAG-repeat expansion in the HD gene was detected. To map the disease trait segregating in this family, whole-genome screening with highly polymorphic dinucleotide-, trinucleotide-, and tetranucleotide-repeat DNA markers was performed. A positive LOD score of 3.01 was obtained for the marker D20S482 on chromosome 20p, by two-point LOD-score analysis with the MLINK program. Haplotype analysis indicated that the gene responsible for the disease is likely located in a 2.7-cM region between the markers D20S193 and D20S895. Candidate genes from the mapping region were screened for mutations.
Xiang
F
F
Department of Molecular Medicine, Karolinska Hospital, Stockholm, Sweden.
Almqvist
E W
EW
Huq
M
M
Lundin
A
A
Hayden
M R
MR
Edström
L
L
Anvret
M
M
Zhang
Z
Z
D000328:Adult; D017668:Age of Onset; D001284:Atrophy; D001921:Brain / Q000473:pathology; D002874:Chromosome Mapping; D002890:Chromosomes, Human, Pair 20; D002894:Chromosomes, Human, Pair 4; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D006816:Huntington Disease / Q000235:genetics* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D013548:Sweden; D018911:Trinucleotide Repeats
D005819:Genetic Markers