JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
African-American TOMM40'523-APOE haplotypes are admixture of West African and Caucasian alleles.
Alzheimers Dement
PUBLISHED: 05-01-2014
Show Abstract
Hide Abstract
Several studies have demonstrated a lower apolipoprotein E4 (APOE ?4) allele frequency in African-Americans, but yet an increased age-related prevalence of AD. An algorithm for prevention clinical trials incorporating TOMM40'523 (Translocase of Outer Mitochondria Membrane) and APOE depends on accurate TOMM40'523-APOE haplotypes.
Related JoVE Video
The genetic contributions of SNCA and LRRK2 genes to Lewy Body pathology in Alzheimer's disease.
Hum. Mol. Genet.
PUBLISHED: 04-28-2014
Show Abstract
Hide Abstract
The molecular genetic basis that leads to Lewy Body (LB) pathology in 15-20% of Alzheimer disease cases (LBV/AD) was largely unknown. Alpha-synuclein (SNCA) and Leucine-rich repeat kinase2 (LRRK2) have been implicated in the pathogenesis of Parkinson's disease (PD), the prototype of LB spectrum disorders. We tested the association of SNCA variants with LB pathology in AD. We then stratified the SNCA association analyses by LRRK2 genotype. We also investigated the expression regulation of SNCA and LRRK2 in relation to LB pathology. We evaluated the differences in SNCA-mRNA and LRRK2-mRNA levels as a function of LB pathology in the temporal cortex (TC) from autopsy-confirmed LBV/AD cases and AD controls. We further investigated the cis-effect of the LB pathology-associated genetic variants within the SNCA and LRRK2 loci on the mRNA expression of these genes. SNCA SNPs rs3857059 and rs2583988 showed significant associations with increased risk for LB pathology. When the analyses were stratified by LRRK2-rs1491923 genotype, the associations became stronger for both SNPs and an association was also observed with rs2619363. Expression analysis demonstrated that SNCA- and LRRK2-mRNA levels were significantly higher in TC from LBV/AD brains compared with AD controls. Furthermore, SNCA-mRNA expression level in the TC was associated with rs3857059; homozygotes for the minor allele showed significant higher expression. LRRK2-transcript levels were increased in carriers of rs1491923 minor allele. Our findings demonstrated that SNCA contributes to LB pathology in AD patients, possibly via interaction with LRRK2, and suggested that expression regulation of these genes may be the molecular basis underlying the observed LB associations.
Related JoVE Video
The cis-regulatory effect of an Alzheimer's disease-associated poly-T locus on expression of TOMM40 and apolipoprotein E genes.
Alzheimers Dement
PUBLISHED: 01-15-2014
Show Abstract
Hide Abstract
We investigated the genomic region spanning the Translocase of the Outer Mitochondrial Membrane 40-kD (TOMM40) and Apolipoprotein E (APOE) genes, that has been associated with the risk and age of onset of late-onset Alzheimer's disease (LOAD) to determine whether a highly polymorphic, intronic poly-T within this region (rs10524523; hereafter, 523) affects expression of the APOE and TOMM40 genes. Alleles of this locus are classified as S, short; L, long; and VL, very long based on the number of T residues.
Related JoVE Video
A comparison of the Cambridge Automated Neuropsychological Test Battery (CANTAB) with "traditional" neuropsychological testing instruments.
J Clin Exp Neuropsychol
PUBLISHED: 02-27-2013
Show Abstract
Hide Abstract
The Cambridge Neuropsychological Test Automated Battery (CANTAB) is frequently used in research protocols and increasingly in clinical practice. Despite the frequency of its use, important aspects of its measurement validity have yet to be established in healthy adults. Two hundred and fifty-five individuals completed the CANTAB and traditional neuropsychological tests commonly used in clinical practice, including selected subtests from the Wechsler Adult Intelligence Scale, Controlled Oral Word Association Test, Animal Naming, Trail Making Tests A and B, the Stroop test, and the Green Story Recall test. Results showed that CANTAB subtests were modestly correlated with traditional subtests. Correlations between CANTAB subtests and traditional subtests were less consistent when age and education were controlled for. In conclusion, the CANTAB shows modest associations with traditional neuropsychological test measures.
Related JoVE Video
Contribution of pastimes and testing strategies to the performance of healthy volunteers on cognitive tests.
Clin Neuropsychol
PUBLISHED: 07-04-2011
Show Abstract
Hide Abstract
Clinicians routinely query factors known to impact cognitive test scores, including age and education. However, without data delineating the impact of less-frequently tracked variables, clinicians are limited to educated inferences about their effect. We explored the relationship of demographics, pastimes, and strategies with cognitive scores in a sample of 499 healthy young volunteers. As expected, age, education, ethnicity, and native language were strongly associated with most tests, while gender and dysphoria were associated with only some. Interestingly, pastimes such as playing number games and word games, and doing activities similar to the tests, were strongly associated with many measures, and testing strategies with almost all. Importantly, at least an additional 50% of the variation in Digit Span Backward and Animals scores was explained by adding covariates about pastimes and strategies to demographic covariates. These results support the utility of querying these elements.
Related JoVE Video
The effect of SNCA 3 region on the levels of SNCA-112 splicing variant.
Neurogenetics
PUBLISHED: 08-16-2010
Show Abstract
Hide Abstract
Genetic variability at the 3 region of SNCA locus has been repeatedly associated with susceptibility to sporadic Parkinsons disease (PD). Accumulated evidence emphasizes the importance of SNCA dosage and expression levels in PD pathogenesis. However, the mechanism through which the 3 region of SNCA gene modulates the risk to develop sporadic PD remained elusive. We studied the effect of PD risk-associated variants at SNCA 3 regions on SNCA112-mRNA (exon 5 in-frame skipping) levels in vivo in 117 neuropathologically normal, human brain frontal cortex samples. SNPs tagging the SNCA 3 showed significant effects on the relative levels of SNCA112-mRNA from total SNCA transcripts levels. The "risk" alleles were correlated with increased expression ratio of SNCA112-mRNA from total. We provide evidence for functional consequences of PD-associated SNCA gene variants at the 3 region, suggesting that genetic regulation of SNCA splicing plays an important role in the development of the disease. Further studies to determine the definite functional variant/s within SNCA 3and to establish their association with PD pathology are necessary.
Related JoVE Video
The Alzheimers associated 5 region of the SORL1 gene cis regulates SORL1 transcripts expression.
Neurobiol. Aging
PUBLISHED: 06-03-2010
Show Abstract
Hide Abstract
SORL1 has been identified as a major contributor to late onset Alzheimers disease (LOAD). We test whether genetic variability in the 5 of SORL1 gene modulates the risk to develop LOAD via regulation of SORL1-messenger ribonucleic acid (mRNA) expression and splicing. Two brain structures, differentially vulnerable to LOAD pathology, were examined in 144 brain samples from 92 neurologically normal individuals. The temporal cortex, which is more susceptible to Alzheimers pathology, demonstrated ?2-fold increase in SORL1-mRNA levels in carriers of the minor alleles at single nucleotide polymorphisms (SNPs), rs7945931 and rs2298525, compared with noncarriers. No genetic effect on total-SORL1-mRNA levels was detected in the frontal cortex. However, rs11600875 minor allele was associated with significantly increased levels of exon-2 skipping, but only in frontal cortex. No correlation of SORL1-mRNAs expression was found between frontal and temporal cortexes. Collectively, these indicate the brain region specificity of the genetic regulation of SORL1 expression. Our results suggest that genetic regulation of SORL1 expression plays a role in disease risk and may be responsible for the reported LOAD associations. Further studies to detect the actual pathogenic variant/s are necessary.
Related JoVE Video
Impact of gene variants on sex-specific regulation of human Scavenger receptor class B type 1 (SR-BI) expression in liver and association with lipid levels in a population-based study.
BMC Med. Genet.
PUBLISHED: 01-19-2010
Show Abstract
Hide Abstract
Several studies have noted that genetic variants of SCARB1, a lipoprotein receptor involved in reverse cholesterol transport, are associated with serum lipid levels in a sex-dependent fashion. However, the mechanism underlying this gene by sex interaction has not been explored.
Related JoVE Video
Genetic regulation of alpha-synuclein mRNA expression in various human brain tissues.
PLoS ONE
PUBLISHED: 07-03-2009
Show Abstract
Hide Abstract
Genetic variability across the SNCA locus has been repeatedly associated with susceptibility to sporadic Parkinsons disease (PD). Accumulated evidence emphasizes the importance of SNCA dosage and expression levels in PD pathogenesis. However whether genetic variability in the SNCA gene modulates the risk to develop sporadic PD via regulation of SNCA expression remained elusive. We studied the effect of PD risk-associated variants at SNCA 5 and 3regions on SNCA-mRNA levels in vivo in 228 human brain samples from three structures differentially vulnerable to PD pathology (substantia-nigra, temporal- and frontal-cortex) obtained from 144 neurologically normal cadavers. The extensively characterized PD-associated promoter polymorphism, Rep1, had an effect on SNCA-mRNA levels. Homozygous genotype of the protective, Rep1-259 bp allele, was associated with lower levels of SNCA-mRNA relative to individuals that carried at least one copy of the PD-risk associated alleles, amounting to an average decrease of approximately 40% and >50% in temporal-cortex and substantia-nigra, respectively. Furthermore, SNPs tagging the SNCA 3-untranslated-region also showed effects on SNCA-mRNA levels in both the temporal-cortex and the substantia-nigra, although, in contrast to Rep1, the decreased-risk alleles were correlated with increased SNCA-mRNA levels. Similar to Rep1 findings, no difference in SNCA-mRNA level was seen with different SNCA 3SNP alleles in the frontal-cortex, indicating there is brain-region specificity of the genetic regulation of SNCA expression. We provide evidence for functional consequences of PD-associated SNCA gene variants in disease relevant brain tissues, suggesting that genetic regulation of SNCA expression plays an important role in the development of the disease.
Related JoVE Video
Expansion of the Parkinson disease-associated SNCA-Rep1 allele upregulates human alpha-synuclein in transgenic mouse brain.
Hum. Mol. Genet.
PUBLISHED: 06-04-2009
Show Abstract
Hide Abstract
Alpha-synuclein (SNCA) gene has been implicated in the development of rare forms of familial Parkinson disease (PD). Recently, it was shown that an increase in SNCA copy numbers leads to elevated levels of wild-type SNCA-mRNA and protein and is sufficient to cause early-onset, familial PD. A critical question concerning the molecular pathogenesis of PD is what contributory role, if any, is played by the SNCA gene in sporadic PD. The expansion of SNCA-Rep1, an upstream, polymorphic microsatellite of the SNCA gene, is associated with elevated risk for sporadic PD. However, whether SNCA-Rep1 is the causal variant and the underlying mechanism with which its effect is mediated by remained elusive. We report here the effects of three distinct SNCA-Rep1 variants in the brains of 72 mice transgenic for the entire human SNCA locus. Human SNCA-mRNA and protein levels were increased 1.7- and 1.25-fold, respectively, in homozygotes for the expanded, PD risk-conferring allele compared with homozygotes for the shorter, protective allele. When adjusting for the total SNCA-protein concentration (endogenous mouse and transgenic human) expressed in each brain, the expanded risk allele contributed 2.6-fold more to the SNCA steady-state than the shorter allele. Furthermore, targeted deletion of Rep1 resulted in the lowest human SNCA-mRNA and protein concentrations in murine brain. In contrast, the Rep1 effect was not observed in blood lysates from the same mice. These results demonstrate that Rep1 regulates human SNCA expression by enhancing its transcription in the adult nervous system and suggest that homozygosity for the expanded Rep1 allele may mimic locus multiplication, thereby elevating PD risk.
Related JoVE Video
Pleiotropy and allelic heterogeneity in the TOMM40-APOE genomic region related to clinical and metabolic features of hepatitis C infection.
Hum. Genet.
Show Abstract
Hide Abstract
Hepatitis C virus (HCV) modulates host lipid metabolism as part of its lifecycle and is dependent upon VLDL for co-assembly and secretion. HCV dyslipidemia is associated with steatosis, insulin resistance, IL28B genotype and disease progression. Apolipoprotein E (ApoE) is an important lipid transport protein, a key constituent of VLDL, and is involved in immunomodulation. Our aims were to determine the role of APOE regional polymorphisms on host lipids, IL28B genotype and disease severity in chronic HCV (CHC) patients. The study cohort included 732 CHC patients with available DNA for genotype determination of four polymorphisms in the chromosome 19 region that encompasses the TOMM40, APOE and APOC1 genes. Serum lipid analysis and apolipoproteins levels were measured using an immunoturbidimetric assay. APOE rs7412 polymorphism (capturing the ?2 isoform) was significantly associated with serum ApoE levels in both Caucasians and African-American patients (p = 2.3 × 10(-11)) and explained 7 % of variance in serum ApoE. Among IL28B-CC patients (n = 196), the rs429358 (defines ?4 isoform) and TOMM40 523 S polymorphisms were associated with 12 % of variance in ApoB levels. Patients homozygous for the APOE ?3 isoform had a greater than twofold increased odds of F2-F4 fibrosis (p = 1.8 × 10(-5)), independent of serum lipid and lipoprotein levels. There were no associations between APOE polymorphisms and serum HDL-C, APO-CIII and triglycerides. In CHC patients, genetic heterogeneity in the APOE/TOMM40 genomic region is significantly associated with variation in serum ApoE and ApoB levels, and also with fibrosis suggesting a pleiotropic attribute of this genomic region.
Related JoVE Video
Characterization of the poly-T variant in the TOMM40 gene in diverse populations.
PLoS ONE
Show Abstract
Hide Abstract
We previously discovered that a polymorphic, deoxythymidine-homopolymer (poly-T, rs10524523) in intron 6 of the TOMM40 gene is associated with age-of-onset of Alzheimers disease and with cognitive performance in elderly. Three allele groups were defined for rs10524523, hereafter 523, based on the number of T-residues: Short (S, T?19), Long (L, 20?T?29) and Very Long (VL, T?30). Homopolymers, particularly long homopolymers like 523, are difficult to genotype because slippage occurs during PCR-amplification. We initially genotyped this locus by PCR-amplification followed by Sanger-sequencing. However, we recognized the need to develop a higher-throughput genotyping method that is also accurate and reliable. Here we describe a new 523 genotyping assay that is simple and inexpensive to perform in a standard molecular genetics laboratory. The assay is based on the detection of differences in PCR-fragment length using capillary electrophoresis. We discuss technical problems, solutions, and the steps taken for validation. We employed the novel assay to investigate the 523 allele frequencies in different ethnicities. Whites and Hispanics have similar frequencies of S/L/VL alleles (0.45/0.11/0.44 and 0.43/0.09/0.48, respectively). In African-Americans, the frequency of the L-allele (0.10) is similar to Whites and Hispanics; however, the S-allele is more prevalent (0.65) and the VL-allele is concomitantly less frequent (0.25). The allele frequencies determined using the new methodology are compared to previous reports for Ghanaian, Japanese, Korean and Han Chinese cohorts. Finally, we studied the linkage pattern between TOMM40-523 and APOE alleles. In Whites and Hispanics, consistent with previous reports, the L is primarily linked to ?4, while the majority of the VL and S are linked to ?3. Interestingly, in African-Americans, Ghanaians and Japanese, there is an increased frequency of the 523S-APOE?4 haplotype. These data may be used as references for 523 allele and 523-APOE haplotype frequencies in diverse populations for the design of research studies and clinical trials.
Related JoVE Video

What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.