Association of Single-Nucleotide Polymorphisms of the Tau Gene With Late-Onset Parkinson Disease

Martin, Eden R.; Scott, William K.; Nance, Martha; Watts, Ray L.; Hubble, Jean; Koller, William C.; Lyons, Kelly; Pahwa, Rajesh; Stern, Matthew B.; Colcher, Amy; Hiner, Bradley C.; Jankovic, Joseph; Ondo, William G.; Allen, Fred H.; Goetz, Christopher G.; Small, Gary W.; Masterman, Donna; Mastaglia, Frank; Laing, Nigel G.; Stajich, Jeffrey M.; Ribble, R.; Booze, Michael W.; Rogala, Allison R.; Hauser, Michael A.; Zhang, Fengyu; Gibson, Rachel A.; Middleton, Lefkos; Roses, Allen D.; Haines, Jonathan L.; Scott, Burton L.; Pericak‐Vance, Margaret A.; Vance, Jeffery M.

doi:10.1001/jama.286.18.2245

Cited by 177 publications

(98 citation statements)

References 25 publications

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“…31 None of the SNP variations cause coding changes, but the exon 6 splice site SNP is predicted to have an effect on splice site choice. 31 The 5 0 UTR marker was genotyped using a modification of the gel-based oligonucleotide ligation assay (OLA), 44 as described by Martin et al 45 Genotyping of all SNPs was carried out with TaqMan assays from Applied Biosystems. 46 Table 2 gives positional information about the RELN markers, most of which are located in GenBank cosmid F19374.…”

Section: Molecular Analysesmentioning

confidence: 99%

Analysis of the RELN gene as a genetic risk factor for autism

et al. 2004

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Several genome-wide screens have indicated the presence of an autism susceptibility locus within the distal long arm of chromosome 7 (7q). Mapping at 7q22 within this region is the candidate gene reelin (RELN). RELN encodes a signaling protein that plays a pivotal role in the migration of several neuronal cell types and in the development of neural connections. Given these neurodevelopmental functions, recent reports that RELN influences genetic risk for autism are of significant interest. The total data set consists of 218 Caucasian families collected by our group, 85 Caucasian families collected by AGRE, and 68 Caucasian families collected at Tufts University were tested for genetic association of RELN variants to autism. Markers included five single-nucleotide polymorphisms (SNPs) and a repeat in the 5 0 -untranslated region (5 0 -UTR). Tests for association in Duke and AGRE families were also performed on four additional SNPs in the genes PSMC2 and ORC5L, which flank RELN. Familybased association analyses (PDT, Geno-PDT, and FBAT) were used to test for association of single-locus markers and multilocus haplotypes with autism. The most significant association identified from this combined data set was for the 5 0 -UTR repeat (PDT P-value ¼ 0.002). These analyses show the potential of RELN as an important contributor to genetic risk in autism.

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Section: Molecular Analysesmentioning

confidence: 99%

Analysis of the RELN gene as a genetic risk factor for autism

et al. 2004

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“…18,19 In contrast, the H2 haplotype seems to be related to familial FTD 20 -22 and it has been reported to anticipate the age at onset of sporadic FTD. 23,24 However, the role of MAPT regarding the fundamental disease process is still unclear.…”

Section: Introductionmentioning

confidence: 99%

H1 haplotype of the MAPT gene is associated with lower regional gray matter volume in healthy carriers

et al. 2008

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The microtubule-associated protein Tau (MAPT) gene codes for the protein Tau that is involved in the pathogenesis of neurodegenerative diseases. Recent studies have detected an over-representation of the H1 haplotype of the MAPT gene in neurodegenerative disorders such as progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), frontotemporal dementia (FTD) and Parkinson's disease (PD), whereas the H2 haplotype has been found to be related to familial FTD. We aimed to investigate the association between MAPT haplotype status and brain morphology in healthy adults. A total of 150 healthy subjects underwent 3D high-resolution magnetic resonance (MR). MR images were processed following an optimized protocol to perform the Voxel-based morphometry (VBM) comparisons of the gray matter (GM) in H1 carriers (n ¼ 141) in contrast to H2H2 homozygous (n ¼ 9), and H1H1 homozygous (n ¼ 85) in contrast to H2 carriers (n ¼ 65). The threshold for statistical significance was 0.005 uncorrected. Opposite comparisons were also carried out. The groups had similar demographic and cognitive features. Compared with H2H2, the H1 carriers showed up to 19% smaller GM volume in the head of the right caudate nucleus, in the right middle frontal gyrus, in the left insula and orbito-frontal cortex, and in the inferior temporal and inferior cerebellar lobes, bilaterally. Compared with all H2 carriers, H1H1 displayed lower GM in the same regions, but the effect was smaller (5%), possibly due to a dilution effect by H1 in the H2 carriers group. The data suggest that H1 haplotype is associated with a particular cerebral morphology that may increase the susceptibility of the healthy carriers to develop neurodegenerative diseases such as sporadic tauopathies.

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“…For example, in typical, late-onset Parkinson Disease, a neurodegenerative disorder that is associated with a reduction of dopaminergic activity in the substantia nigra, tracking down disease-causing genes has been elusive. However, the existence of "susceptibility" genes has been suggested (Martin et al, 2001), particularly in the context of the alleged disease-causing role of environmental toxins (Checkoway and Nelson, 1999). Several twin studies have so far been unable to identify genetic factors (Ward et al, 1983;Tanner et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Functional genomics of neural and behavioral plasticity

2002

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How does the environment, particularly the social environment, influence brain and behavior and what are the underlying physiologic, molecular, and genetic mechanisms? Adaptations of brain and behavior to changes in the social or physical environment are common in the animal world, either as short-term (i.e., modulatory) or as long-term modifications (e.g., via gene expression changes) in behavioral or physiologic properties. The study of the mechanisms and constraints underlying these dynamic changes requires model systems that offer plastic phenotypes as well as a sufficient level of quantifiable behavioral complexity while being accessible at the physiological and molecular level. In this article, I explore how the new field of functional genomics can contribute to an understanding of the complex relationship between genome and environment that results in highly plastic phenotypes. This approach will lead to the discovery of genes under environmental control and provide the basis for the study of the interrelationship between an individual's gene expression profile and its social phenotype in a given environmental context.

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Association of Single-Nucleotide Polymorphisms of the Tau Gene With Late-Onset Parkinson Disease

Abstract: This integrated approach of genetic linkage and positional association analyses implicates tau as a susceptibility gene for idiopathic PD.

Cited by 177 publications

References 25 publications

Analysis of the RELN gene as a genetic risk factor for autism

Analysis of the RELN gene as a genetic risk factor for autism

H1 haplotype of the MAPT gene is associated with lower regional gray matter volume in healthy carriers

Functional genomics of neural and behavioral plasticity

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