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History of genetic disease

The molecular genetics of Huntington disease — a history

Abstract

The Huntington disease gene was mapped to human chromosome 4p in 1983 and 10 years later the pathogenic mutation was identified as a CAG-repeat expansion. Our current understanding of the molecular pathogenesis of Huntington disease could never have been achieved without the recent progress in the field of molecular genetics. We are now equipped with powerful genetic models that continue to uncover new aspects of the pathogenesis of Huntington disease and will be instrumental for the development of therapeutic approaches for this disease.

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Figure 1: George Huntington as a young man.
Figure 2: Max Perutz at the Royal Institution in London in 1994.

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Author information

Authors and Affiliations

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Related links

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DATABASES

Entrez Gene

DMPK

FMR1

HD

MedlinePlus

doxycycline

OMIM

Alzheimer disease

Fragile X syndrome

Huntington disease

Myotonic dystrophy

Parkinson disease

Spinal and bulbar muscular atrophy

FURTHER INFORMATION

Department of Medical and Molecular Genetics, King's College London

Euro-HD Network

HDbase

Hereditary Disease Foundation

High Q Foundation

Human Genome Project

Huntington Project

Huntington's Disease Society of America

Huntington Study Group

Glossary

ANTICIPATION

A phenomenon whereby a disease develops an earlier onset, or more severe symptoms, as it is transmitted through the generations.

BIALLELIC

A locus at which there are two possible variations of a given DNA sequence that are detectable in the human population.

CLONE CONTIG

A linear series of DNA clones with overlapping inserts.

EXCITOTOXICITY

The over-stimulation of excitatory neurotransmitter receptors, which causes an influx of calcium in the postsynaptic neuron.

EXON TRAPPING

A specialized vector containing splice sites that will splice to and isolate exons that are contained within the genomic insert.

FRAGILE X SYNDROME

The most common form of human X-chromosome-linked mental retardation that is associated with a folate-sensitive fragile site at Xq27.3.

HETEROGENEOUS

A description of a genetic disease that is caused by mutations in different genes.

LINKAGE DISEQUILIBRIUM

Non-random association of alleles at genetically linked loci.

LINKING LIBRARIES

Genomic libraries of rare cutter restriction sites and their flanking DNA.

MYOTONIC DYSTROPHY

An autosomal-dominant disease with variable symptoms. The mild form exhibits cataracts that develop in mid to old age, the adult form shows myotonia and muscle weakness, and the most severe form is congenital with a high rate of neonatal mortality. Myotonic dystrophy shows pronounced anticipation on maternal inheritance.

PULSED-FIELD GEL ELECTROPHORESIS

An electrophoretic technique that is used to separate large fragments of DNA (20 kb and up to 10 Mb) on an agarose gel by periodically changing the orientation of the electrical field that is applied to the gel.

RADIATION HYBRID

A type of somatic-cell hybrid in which fragments of chromosomes of one cell type are generated by exposure to X-rays and are subsequently allowed to integrate into the chromosomes of a second cell type.

RARE CUTTER RESTRICTION FRAGMENT

Fragments generated by restriction endonucleases that cut infrequently in the genome either because the recognition sequence is large or because it contains one or more copies of the CpG dinucleotide.

RESTRICTION FRAGMENT-LENGTH POLYMORPHISM

A fragment-length variant that is generated through the presence or absence of a restriction-enzyme recognition site. Restriction sites can be gained or lost by base substitutions, insertions or deletions.

SOMATIC-CELL HYBRID

An artificially constructed cell in which chromosomes have been stably introduced from cells of a different species.

SPINAL AND BULBAR MUSCULAR ATROPHY

An X-chromosome-linked mild form of motor neuron disease.

VARIABLE NUMBER OF TANDEM REPEATS LOCUS

A locus that contains a variable number of short tandemly repeated DNA sequences that vary in length and are highly polymorphic.

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Bates, G. The molecular genetics of Huntington disease — a history. Nat Rev Genet 6, 766–773 (2005). https://doi.org/10.1038/nrg1686

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