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| 2. |
- Ahmadi, Ahmad, et al.
(author)
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Association of a protective paraoxonase 1 (PON1) polymorphism in Parkinson's disease
- 2012
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In: Neuroscience Letters. - : Elsevier BV. - 0304-3940 .- 1872-7972. ; 522:1, s. 30-35
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Journal article (peer-reviewed)abstract
- Pesticide exposure has been suggested to increase the risk to develop Parkinson's disease (PD). The arylesterase paraoxonase 1 (PON1) is mainly expressed in the liver and hydrolyzes organophosphates such as pesticides. The polymorphism Leu54Met (rs854560) in PON1, impairing enzyme activity and leading to decreased PON1 expression levels, has been reported to be associated with Parkinson's disease (PD). PON1 is part of a cluster on chromosome 7q21.3 together with PON2 and PON3. We investigated the occurrence of four additional polymorphisms in PON1 and two in PON2 in a Swedish PD case-control material. We found a significant association (p = 0.007) with a PON1 promoter polymorphism, rs854571. The minor allele was more common among controls than PD cases which suggest a protective effect. This is strengthened by the fact that rs854571 is in strong linkage disequilibrium with another PON1 promoter polymorphism, rs854572, reported to increase PON1 gene expression. Our findings support the hypothesis that PON1 is involved in the etiology of PD and that higher PON1 levels are reducing the risk for PD. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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| 6. |
- Xiang, F, et al.
(author)
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A Huntington disease-like neurodegenerative disorder maps to chromosome 20p.
- 1998
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In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 63:5, s. 1431-8
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Journal article (peer-reviewed)abstract
- 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.
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| 7. |
- Zhang, ZP, et al.
(author)
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A new approach to gene therapy
- 1997
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In: Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis. - 0957-5235. ; 88 Suppl 2, s. S39-S42
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Journal article (peer-reviewed)
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| 11. |
- Andrew, S, et al.
(author)
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DNA analysis of distinct populations suggests multiple origins for the mutation causing Huntington disease.
- 1993
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In: Clinical Genetics. - 0009-9163 .- 1399-0004. ; 43:6, s. 286-94
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Journal article (peer-reviewed)abstract
- Results of association studies can be significantly biased if the ancestry of the control population is not similar to that of the affected population. One approach to overcome such a bias is to use distinct populations where controls and affected individuals are likely to be of similar descent. We have examined homogeneous populations of French, Danish and Swedish ancestry for nonrandom allelic association between Huntington disease (HD) and several markers previously shown to be in association with HD. No evidence for nonrandom allelic association between HD and these markers was shown in these populations. The demonstration of association in a United Kingdom (UK) sample of similar size, and lack of significant differences in allele frequencies between the French, Danish, Swedish and UK populations suggested that the absence of association was not predominantly a consequence of allele frequencies or sample size. To investigate further the number of potential HD chromosomes, DNA haplotypes were constructed for the Danish, French, Swedish and UK populations. The minimum of two HD haplotypes observed in each of the French, Danish and Swedish populations, compared to the one haplotype in the UK population of a similar size, is an important factor accounting for the absence of association between HD and the DNA markers in these populations. Furthermore, these data are in favour of multiple independent origins for the mutation causing HD.
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| 17. |
- Holmgren, G, et al.
(author)
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Linkage of G8 (D4S10) in two Swedish families with Huntington's disease.
- 1987
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In: Clinical Genetics. - 0009-9163 .- 1399-0004. ; 32:5, s. 289-94
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Journal article (peer-reviewed)abstract
- Two Swedish families with Huntington's disease (HD) have been investigated for linkage with G8 (D4S10). In one family from northern Sweden (Family 1) 48 family members were examined, and in another family from the southwestern part of Sweden (Family 2) 14 family members were examined. The lod scores were 1.531 for Family 1 and 2.057 for Family 2, and the combined lod score was 3.59. The HD gene was segregating with the haplotype C in Family 1 and with haplotype A in Family 2. The predictive value of the test was obvious. Before the testing with the G8 probe, 84.2% of the family members in Family 1 had a theoretical risk of 25% or 50% of having the HD gene. After the testing with the G8 probe, only 23.7% of the family members remained at the same risk, and it could also be certified that 63.2% had no or little risk of having the HD gene. Only one asymptomatic person was predicted to have HD.
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| 22. |
- Ran, C, et al.
(author)
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Genetic Variations and mRNA Expression of NRF2 in Parkinson's Disease
- 2017
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In: Parkinson's disease. - : Hindawi Limited. - 2090-8083 .- 2042-0080. ; 2017, s. 4020198-
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Journal article (peer-reviewed)abstract
- Nuclear factor erythroid 2-like 2 (NRF2) encodes a transcription factor regulating mechanisms of cellular protection and is activated by oxidative stress. NRF2 has therefore been hypothesized to confer protection against Parkinson’s disease and so far an NRF2 haplotype has been reported to decrease the risk of developing disease and delay disease onset. Also NRF2 adopts a nuclear localization in Parkinson’s disease, which is indicative of increased NRF2 activity. We have investigated the association between NRF2 and Parkinson’s disease in a Swedish case-control material and whether NRF2 expression levels correlate with NRF2 genetic variants, disease, or disease onset. Using pyrosequencing, we genotyped one intronic and three promoter variants in 504 patients and 509 control subjects from Stockholm. Further, we quantified NRF2 mRNA expression in EBV transfected human lymphocytes from patients and controls using quantitative real-time reverse transcription PCR. We found that one of the promoter variants, rs35652124, was associated with age of disease onset (Χ2 = 14.19, p value = 0.0067). NRF2 mRNA expression levels however did not correlate with the rs35652124 genotype, Parkinson’s disease, or age of onset in our material. More detailed studies on NRF2 are needed in order to elucidate how this gene affects pathophysiology of Parkinson’s disease.
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| 32. |
- Almqvist, E, et al.
(author)
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Ancestral differences in the distribution of the delta 2642 glutamic acid polymorphism is associated with varying CAG repeat lengths on normal chromosomes : insights into the genetic evolution of Huntington disease.
- 1995
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 4:2, s. 207-14
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Journal article (peer-reviewed)abstract
- This study addresses genetic factors associated with normal variation of the CAG repeat in the Huntington disease (HD) gene. To achieve this, we have studied patterns of variation of three trinucleotide repeats in the HD gene including the CAG and adjacent CCG repeats as well as a GAG polymorphism at residue 2642 (delta 2642). We have previously demonstrated that variation in the CCG repeat is associated with variation of the CAG repeat length on normal chromosomes. Here we show that differences in the GAG trinucleotide polymorphism at residue 2642 is also significantly correlated with CAG size on normal chromosomes. The B allele which is associated with higher CAG repeat lengths on normal chromosomes is markedly enriched on affected chromosomes. Furthermore, this glutamic acid polymorphism shows significant variation in different ancestries and is absent in chromosomes of Japanese, Black and Chinese descent. Haplotype analysis of both the CCG and delta 2642 polymorphisms have indicated that both are independently associated with differences in CAG length on normal chromosomes. These findings lead to a model for the genetic evolution of new mutations for HD preferentially occurring on normal chromosomes with higher CAG repeat lengths and a CCG repeat length of seven and/or a deletion of the glutamic acid residue at delta 2642. This study also provides additional evidence for genetic contributions to demographic differences in prevalence rates for HD.
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| 33. |
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| 34. |
- Andrew, S E, et al.
(author)
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Huntington disease without CAG expansion : phenocopies or errors in assignment?
- 1994
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In: American Journal of Human Genetics. - 0002-9297 .- 1537-6605. ; 54:5, s. 852-63
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Journal article (peer-reviewed)abstract
- Huntington disease (HD) has been shown to be associated with an expanded CAG repeat within a novel gene on 4p16.3 (IT15). A total of 30 of 1,022 affected persons (2.9% of our cohort) did not have an expanded CAG in the disease range. The reasons for not observing expansion in affected individuals are important for determining the sensitivity of using repeat length both for diagnosis of affected patients and for predictive testing programs and may have biological relevance for the understanding of the molecular mechanism underlying HD. Here we show that the majority (18) of the individuals with normal sized alleles represent misdiagnosis, sample mix-up, or clerical error. The remaining 12 patients represent possible phenocopies for HD. In at least four cases, family studies of these phenocopies excluded 4p16.3 as the region responsible for the phenotype. Mutations in the HD gene that are other than CAG expansion have not been excluded for the remaining eight cases; however, in as many as seven of these persons, retrospective review of these patients' clinical features identified characteristics not typical for HD. This study shows that on rare occasions mutations in other, as-yet-undefined genes can present with a clinical phenotype very similar to that of HD.
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