Presymptomatic, prenatal, and exclusion testing for Huntington disease using seven closely linked DNA markers
American Journal of Medical GeneticsPublished 1 May 1991
M. I. Skraastad, Aart Verwest, Egbert Bakker, M Vegter-van der Vlis, Inge van Leeuwen‐Cornelisse, Raymund A.C. Roos
Citations23
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TL;DR
The results of presymptomatic tests for 37 applicants including two prenatal and one exclusion test in 23 families are presented, with the overall informativity in the data set was 84% and in the most recent test the test achieved a 90-95% informativity.
Abstract
Presymptomatic, testing, prenatal diagnosis, or exclusion testing are now available for persons at risk for Huntington disease. These tests will reduce uncertainty, assist in life planning, and prevent the birth of potentially affected children. We present the results of presymptomatic tests for 37 applicants including two prenatal and one exclusion test in 23 families. We initially used the markers G8, H5.52, F5.53, and pTV20 (D4S10), p8 (D4S62), and pRB1.6 (D4S81) and extended the informativity of the test at a later stage with the markers pKP1.65, C4H, S1.5 (D4S43), 674 (D4S95), 157.9 (D4S111), and YNZ32 (D4S125). Applicants with an unsuitable family structure were not admitted to the test. Of the 37 applicants, 33 were informative. In our hands the most efficient strategy is first to use the markers H5.52 (D4S10), pRB1.6 (D4S81), 674 (D4S95), pKP1.65 (D4S43), 157.9 (D4S111), YNZ32 (D4S125), and 252.3 (D4S115). The overall informativity in our data set was 84% and in the most recent test we achieved a 90-95% informativity. The other markers are used only when the first set is not informative.
Keywords
NeuroscienceBiochemistry, Genetics and Molecular Biology
Nucleic Acids ResearchA simple salting out procedure for extracting DNA from human nucleated cells
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Proceedings of the National Academy of SciencesGenomic sequencing.
8,227 Citations1984George M. Church, W Gilbert
The genomic sequencing procedures are applicable to the analysis of genetic polymorphisms, DNA methylation at deoxycytidines, and nucleic acid-protein interactions at single nucleotide resolution.
NatureA polymorphic DNA marker genetically linked to Huntington's disease
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PubMedHuntington disease: genetics and epidemiology.
204 Citations1984Conneally Pm
The major pathological features of HD are a primary loss of cells in the caudate nucleus and putamen but other regions of the basal ganglia, hypothalamus, and brain stem are also involved.
American Journal of Medical GeneticsAttitudes of persons at risk for Huntington disease toward predictive testing
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NatureA highly polymorphic locus very tightly linked to the Huntington's disease gene
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American Journal of Medical GeneticsIntended use of predictive testing by those at risk for Huntington disease
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Results indicated that a majority (65%) favored using the presymptomatic test and would encourage their adult children to use it as well and the need for outreach and prevention efforts to prepare the at risk and specialized programs of genetic counseling and follow up to accompany predictive testing.
American Journal of Medical GeneticsAt‐risk Persons' attitudes toward presymptomatic and prenatal testing of Huntington disease in Michigan
124 Citations1987Dorene S. Markel, Anne B. Young +3 more
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ScienceA DNA Segment Encoding Two Genes Very Tightly Linked to Huntington's Disease
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Expansion of the D4S43 region to include 108 kilobases of cloned DNA has allowed identification of eight restriction fragment length polymorphisms and at least two independent coding segments, which must be considered candidates for the site of the HD defect.
NeuronRecombination events suggest potential sites for the Huntington's disease gene
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A fine-structure genetic map is produced that establishes the relative order of the clusters and further narrows the target area containing the HD gene.
Journal of Medical GeneticsLinkage disequilibrium in Huntington's disease: an improved localisation for the gene.
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Significant linkage disequilibrium is found between the markers D4S98 andD4S95, which supports a localisation for the gene proximal to D 4S90 and makes a telomeric localisation unlikely.
Journal of Medical GeneticsNon-random association between alleles detected at D4S95 and D4S98 and the Huntington's disease gene.
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It is suggested that it may be possible to construct high and low risk haplotypes, which may be helpful in DNA analysis and genetic counselling for HD, and independent evidence that the gene for HD is centromeric to more distally located DNA markers such as D4S90 is represented.
Clinical GeneticsThe motivation of at‐risk individuals and their partners in deciding for or against predictive testing for Huntington's disease
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BMJGenetic prediction and family structure in Huntington's chorea.
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Analysis of data from a population register for Huntington's chorea in south Wales showed that only a minority of subjects at risk had the appropriate members of their family living to allow the presence or absence of the gene to be definitively predicted.
Journal of Clinical InvestigationClustering of multiallele DNA markers near the Huntington's disease gene.
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PubMedImproved predictive testing for Huntington disease by using three linked DNA markers.
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Nucleic Acids ResearchMapping of<i>D4S98/S114/S113</i>confines the Huntington's defect to a reduced physical region at the telomere of chromosome 4
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The D4S98/S114/S113 cluster therefore represents the nearest cloned sequences to HD, and provides a valuable new point for launching directional cloning strategies to isolate and characterize this disease gene.
Proceedings of the National Academy of SciencesChromosome jumping from D4S10 (G8) toward the Huntington disease gene.
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JAMAPresymptomatic Testing for Huntington's Disease
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Journal of Medical GeneticsPrenatal exclusion testing for Huntington's disease: a problem of too much information.
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PubMedMapping of recombinants near the Huntington disease locus by using G8 (D4S10) and newly isolated markers in the D4S10 region.
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