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Title: Significant linkage disequilibrium between the Huntington disease gene and the loci D4S10 and D4S95 in the Dutch population

Abstract

Significant linkage disequilibrium has been found between the Huntington disease (HD) gene and DNA markers located around D4S95 and D4S98. The linkage-disequilibrium studies favor the proximal location of the HD gene, in contrast to the conflicting results of recombination analyses. The authors have analyzed 45 Dutch HD families with 19 DNA markers and have calculated the strength of linkage disequilibrium. Highly significant linkage disequilibrium has been detected with D4S95, consistent with the studies in other populations. In contrast with most other studies, however, the area of linkage disequilibrium extends from D4S10 proximally to D4S95, covering 1,100 kb. These results confirm that the HD gene most likely maps near D4S95. 28 refs., 1 fig., 2 tabs.

Authors:
; ; ; ; ; ;  [1];  [2]
  1. (Leiden Univ. (Netherlands))
  2. (Univ. Hospital Kijkzigt, Rotterdam (Netherlands))
Publication Date:
OSTI Identifier:
5053473
Alternate Identifier(s):
OSTI ID: 5053473
Resource Type:
Journal Article
Resource Relation:
Journal Name: American Journal of Human Genetics; (United States); Journal Volume: 51:4
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; BIOLOGICAL MARKERS; GENETIC MAPPING; HUMAN CHROMOSOMES; NERVOUS SYSTEM DISEASES; GENE MUTATIONS; CHROMOSOMES; DISEASES; MAPPING; MUTATIONS 550400* -- Genetics

Citation Formats

Skraastad, M.I., Van de Vosse, E., Belfroid, R., Hoeld, K., Vegter-van der Vlis, M., Bakker, E., van Ommen, G.J.B., and Sandkuijl, L.A.. Significant linkage disequilibrium between the Huntington disease gene and the loci D4S10 and D4S95 in the Dutch population. United States: N. p., 1992. Web.
Skraastad, M.I., Van de Vosse, E., Belfroid, R., Hoeld, K., Vegter-van der Vlis, M., Bakker, E., van Ommen, G.J.B., & Sandkuijl, L.A.. Significant linkage disequilibrium between the Huntington disease gene and the loci D4S10 and D4S95 in the Dutch population. United States.
Skraastad, M.I., Van de Vosse, E., Belfroid, R., Hoeld, K., Vegter-van der Vlis, M., Bakker, E., van Ommen, G.J.B., and Sandkuijl, L.A.. Thu . "Significant linkage disequilibrium between the Huntington disease gene and the loci D4S10 and D4S95 in the Dutch population". United States. doi:.
@article{osti_5053473,
title = {Significant linkage disequilibrium between the Huntington disease gene and the loci D4S10 and D4S95 in the Dutch population},
author = {Skraastad, M.I. and Van de Vosse, E. and Belfroid, R. and Hoeld, K. and Vegter-van der Vlis, M. and Bakker, E. and van Ommen, G.J.B. and Sandkuijl, L.A.},
abstractNote = {Significant linkage disequilibrium has been found between the Huntington disease (HD) gene and DNA markers located around D4S95 and D4S98. The linkage-disequilibrium studies favor the proximal location of the HD gene, in contrast to the conflicting results of recombination analyses. The authors have analyzed 45 Dutch HD families with 19 DNA markers and have calculated the strength of linkage disequilibrium. Highly significant linkage disequilibrium has been detected with D4S95, consistent with the studies in other populations. In contrast with most other studies, however, the area of linkage disequilibrium extends from D4S10 proximally to D4S95, covering 1,100 kb. These results confirm that the HD gene most likely maps near D4S95. 28 refs., 1 fig., 2 tabs.},
doi = {},
journal = {American Journal of Human Genetics; (United States)},
number = ,
volume = 51:4,
place = {United States},
year = {Thu Oct 01 00:00:00 EDT 1992},
month = {Thu Oct 01 00:00:00 EDT 1992}
}
  • The neuronal ceroid lipofuscinoses (NCL; Batten disease) are a collection of autosomal recessive disorders characterized by the accumulation of autofluorescent lipopigments in the neurons and other cell types. Clinically, these disorders are characterized by progressive encephalopathy, loss of vision, and seizures. CLN3, the gene responsible for juvenile NCL, has been mapped to a 15-cM region flanked by the marker loci D16S148 and D16S150 on human chromosome 16. CLN2, the gene causing the late-infantile form of NCL (LNCL), is not yet mapped. The authors have used highly informative dinucleoide repeat markers mapping between D16S148 and D16S150 to refine the localization ofmore » CLN3 and to test for linkage to CLN2. The authors find significant linkage disequilibrium between CLN3 and the dinucleotide repeat marker loci D16S288 (X[sup 2](7) = 46.5, P < .005), D16S298 (X[sup 2](6) = 36.6, P < .005), and D16S299 (X[sup 2](7) = 73.8, P < .005), and also a novel RFLP marker at the D16S272 locus (X[sup 2](1) = 5.7, P = .02). These markers all map to 16p12.1. The D16S298/D16S299 haplotype [open quotes]5/4[close quotes] is highly overrepresented, accounting for 54% of CLN3 chromosomes as compared with 8% of control chromosomes (X[sup 2] = 117, df = 1, P < .001). Examination of the haplotypes suggests that the CLN3 locus can be narrowed to the region immediately surrounding these markers in 16p12.1. Analysis of D16S299 in LNCL pedigrees supports the previous finding that CLN3 and CLN2 are different genetic loci. This study also indicates that dinucleotide repeat markers play a valuable role in disequilibrium studies. 23 refs., 1 fig., 4 tabs.« less
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  • The hemochromatosis gene (HFE) maps to 6p21.3 and is less than 1 cM from the HLA class I gene; however, the precise physical location of the gene has remained elusive and controversial. The unambiguous identification of a crossover event within hemochromatosis families is very difficult; it is particularly hampered by the variability of the phenotypic expression as well as by the sex- and age-related penetrance of the disease. For these considerations, traditional linkage analysis could prove of limited value in further refining the extrapolated physical position of HFE. The authors therefore embarked upon a linkage-disequilibrium analysis of HFE and normalmore » chromosomes for the Brittany population. In this report, 66 hemochromatosis families yielding 151 hemochromatosis chromosomes and 182 normal chromosomes were RFLP-typed with a battery of probes, including two newly derived polymorphic markers from the 6.7 and HLA-F loci located 150 and 250 kb telomeric to HLA-A, respectively. The results suggest a strong peak of existing linkage disequilibrium focused within the i82-to-6.7 interval (approximately 250 kb). The zone of linkage disequilibrium is flanked by the i97 locus, positioned 30 kb proximal to i82, and the HLA-F gene, found 250 kb distal to HLA-A, markers of which display no significant association with HFE. These data support the possibility that HFE resides within the 400-kb expanse of DNA between i97 and HLA-F. Alternatively, the very tight association of HLA-A3 and allele 1 of the 6.7 locus, both of which are comprised by the major ancestral or founder HFE haplotype in Brittany, supports the possibility that the disease gene may reside immediately telomeric to the 6.7 locus within the linkage-disequilibrium zone. Additionally, hemochromatosis haplotypes possessing HLA-A11 and the low-frequency HLA-F polymorphism (allele 2) are supportive of a separate founder chromosome containing a second, independently arising mutant allele. 69 refs., 1 fig., 5 tabs.« less
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