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Repeat Length (repeat + length)

Distribution by Scientific Domains

Medical Sciences	59%
Life Sciences	36%

Kinds of Repeat Length

cag repeat length

Selected Abstracts

Heart Rate Variability Declines with Increasing Age and CTG Repeat Length in Patients with Myotonic Dystrophy Type 1

ANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 3 2003
Bradley A. Hardin
Background: Cardiac myopathy manifesting as arrhythmias is common in the neurological disease, myotonic dystrophy type 1 (DM1). The purpose of the present study was to evaluate heart rate variability (HRV) in patients with DM1. Methods: In a multicenter study, history, ECG, and genetic testing were performed in DM1 patients. Results: In 289 patients in whom the diagnosis of DM1 was confirmed by a prolonged cytosine-thymine-guanine (CTG) repeat length the most common ambulatory ECG abnormality was frequent ventricular ectopy (16.3%). The 24-hour time domain parameters of SDNN (SD of the NN interval) and SDANN (SD of the mean NN, 5-minute interval) declined as age and CTG repeat length increased (SDNN: ,8.5 ms per decade, 95% confidence intervals [CI],12.9, ,4.2, ,8.7 ms per 500 CTG repeats, CI ,15.7, ,1.8, r = 0.24, P < 0.001; SDANN: ,8.1 ms per decade, CI ,12.4, ,3.8, ,8.8 ms per 500 CTG repeats, CI ,15.7, ,1.9, r = 0.23, P < 0.001). Short-term frequency domain parameters declined with age only (total power: ,658 ms2 per decade, CI: ,984, ,331, r = 0.23, P < 0.001; low frequency (LF) power ,287 ms2 per decade, CI: ,397, ,178, r = 0.30, P < 0.001; high frequency (HF) power: ,267 ms2 per decade, CI: ,386, ,144, r = 0.25, P < 0.001). The LF/HF ratio increased as the patient aged (0.5 per decade, CI: 0.1, 0.9, r = 0.13, P = 0.03). Conclusions: In DM1 patients a decline in HRV is observed as the patient ages and CTG repeat length increases. A.N.E. 2003; 8(3):227-232 [source]

TATA Box-Binding Protein gene is associated with risk for schizophrenia, age at onset and prefrontal function

GENES, BRAIN AND BEHAVIOR, Issue 4 2009
K. Ohi
Schizophrenia is a common polygenic disease in distinct populations, while spinocerebellar ataxia type 17 (SCA17) is a rare autosomal dominant neurodegenerative disorder. Both diseases involve psychotic symptoms. SCA17 is caused by an expanded polyglutamine tract in the TATA box-binding protein (TBP) gene. In the present study, we investigated the association between schizophrenia and CAG repeat length in common TBP alleles with fewer than 42 CAG repeats in a Japanese population (326 patients with schizophrenia and 116 healthy controls). We found that higher frequency of alleles with greater than 35 CAG repeats in patients with schizophrenia compared with that in controls (p = 0.042). We also examined the correlation between CAG repeats length and age at onset of schizophrenia. We observed a negative correlation between the number of CAG repeats in the chromosome with longer CAG repeats out of two chromosomes and age at onset of schizophrenia (p = 0.020). We further provided evidence that TBP genotypes with greater than 35 CAG repeats, which were enriched in patients with schizophrenia, were significantly associated with hypoactivation of the prefrontal cortex measured by near-infrared spectroscopy during the tower of Hanoi, a task of executive function (right PFC; p = 0.015, left PFC; p = 0.010). These findings suggest possible associations of the genetic variations of the TBP gene with risk for schizophrenia, age at onset and prefrontal function. [source]

Individual differences in allocation of funds in the dictator game associated with length of the arginine vasopressin 1a receptor RS3 promoter region and correlation between RS3 length and hippocampal mRNA

GENES, BRAIN AND BEHAVIOR, Issue 3 2008
A. Knafo
Human altruism is a widespread phenomenon that puzzled evolutionary biologists since Darwin. Economic games illustrate human altruism by showing that behavior deviates from economic predictions of profit maximization. A game that most plainly shows this altruistic tendency is the Dictator Game. We hypothesized that human altruistic behavior is to some extent hardwired and that a likely candidate that may contribute to individual differences in altruistic behavior is the arginine vasopressin 1a (AVPR1a) receptor that in some mammals such as the vole has a profound impact on affiliative behaviors. In the current investigation, 203 male and female university students played an online version of the Dictator Game, for real money payoffs. All subjects and their parents were genotyped for AVPR1a RS1 and RS3 promoter-region repeat polymorphisms. Parents did not participate in online game playing. As variation in the length of a repetitive element in the vole AVPR1a promoter region is associated with differences in social behavior, we examined the relationship between RS1 and RS3 repeat length (base pairs) and allocation sums. Participants with short versions (308,325 bp) of the AVPR1a RS3 repeat allocated significantly (likelihood ratio = 14.75, P = 0.001, df = 2) fewer shekels to the ,other' than participants with long versions (327,343 bp). We also implemented a family-based association test, UNPHASED, to confirm and validate the correlation between the AVPR1a RS3 repeat and monetary allocations in the dictator game. Dictator game allocations were significantly associated with the RS3 repeat (global P value: likelihood ratio ,2 = 11.73, df = 4, P = 0.019). The association between the AVPR1a RS3 repeat and altruism was also confirmed using two self-report scales (the Bardi,Schwartz Universalism and Benevolence Value-expressive Behavior scales). RS3 long alleles were associated with higher scores on both measures. Finally, long AVPR1a RS3 repeats were associated with higher AVPR1a human post-mortem hippocampal messenger RNA levels than short RS3 repeats (one-way analysis of variance (ANOVA): F = 15.04, P = 0.001, df = 14) suggesting a functional molecular genetic basis for the observation that participants with the long RS3 repeats allocate more money than participants with the short repeats. This is the first investigation showing that a common human polymorphism, with antecedents in lower mammals, contributes to decision making in an economic game. The finding that the same gene contributing to social bonding in lower animals also appears to operate similarly in human behavior suggests a common evolutionary mechanism. [source]

Androgen receptor exon 1 CAG repeat length and risk of hepatocellular carcinoma in women

HEPATOLOGY, Issue 1 2002
Ming-Whei Yu
The androgen receptor (AR) gene is localized on chromosome X, and shorter CAG repeats in exon 1 of the AR gene were recently suggested to increase hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) risk among men. To examine whether the relationship between the AR-CAG repeats and HCC was also evident among women, we conducted a case-control study in Taiwan. The number of AR-CAG repeats was determined for 238 women with HCC and 354 unrelated control subjects (comprising 188 first-degree and 166 nonbiological relatives) selected from female relatives of patients with HCC. Women harboring 2 AR alleles with more than 23 CAG repeats had an increased risk of HCC (age-adjusted odds ratio [OR], 1.82; 95% CI, 1.06-3.14), compared with women with only short alleles or a single long allele. The association between harboring 2 AR alleles containing longer CAG repeats and HCC was more striking among HBV carriers (age-adjusted OR for more than 22 repeats, 2.23; 95% CI, 1.14-4.34) and particularly prominent among HBV carriers under age 53 years (age-adjusted OR, 3.16; 95% CI, 1.13-8.82). When CAG repeats were analyzed as a continuous variable, the increase in HCC risk associated with each incremental repeat in the shorter of 2 alleles in a given genotype was statistically significant among women with a first-degree relative with HCC (age-adjusted OR, 1.18; 95% CI, 1.01-1.37). No such relationship was detected among women without the family history. In conclusion, our observations suggest that the AR-CAG alleles may contribute to HCC predisposition among women through a mechanism different from that for men. [source]

Androgen receptor gene polymorphism and the metabolic syndrome in 60,80 years old Norwegian men

INTERNATIONAL JOURNAL OF ANDROLOGY, Issue 3 2010
Paal André Skjærpe
Summary The metabolic syndrome (MS) includes a clustering of metabolic derangements. Low testosterone levels have been shown to be associated with both components of MS and MS per se. As most androgen-related effects are mediated thorough the androgen receptor (AR), we wanted to investigate to which degree the AR CAG and GGN repeat polymorphisms might be related to MS. Sixty-eight men, 60,80 years old, with subnormal total testosterone levels (,11.0 nmol/L) and 104 men with normal levels (>11.0 nmol/L), participating in a nested case,control study were investigated in this study. Body weight, height, waist circumferences and blood pressure were measured. Fasting blood samples were drawn and an oral glucose tolerance test (OGTT) was performed. The CAG and GGN polymorphisms in the AR gene were determined by direct sequencing of leucocyte DNA. Men with MS had lower CAG repeat number than healthy men (p = 0.007). There were, however, no difference in CAG or GGN repeats length between the groups with subnormal or normal testosterone concentrations. In cross-sectional analyses, men with CAG repeat lengths , 21 had significantly higher fasting glucose, C-peptide and glycosylated haemoglobin (HbA1c) levels (all p < 0.05). In multiple regression analyses, CAG repeat length was an inverse and independent predictor of glucose after an OGTT and of HbA1c levels. We also found that men with more than one component of MS had shorter CAG repeat number (p for trend 0.013) than those with only one component. In conclusion, there were no associations with GGN repeat length, while short CAG repeat length seems to be associated with increased risk of MS. [source]

The CAG repeat polymorphism within the androgen receptor gene and maleness,

INTERNATIONAL JOURNAL OF ANDROLOGY, Issue 2 2003
Michael Zitzmann
Summary The androgen testosterone and its metabolite dihydrotestosterone exert their effects on gene expression and thus effect maleness via the androgen receptor (AR). A diverse range of clinical conditions starting with complete androgen insensitivity has been correlated with mutations in the AR. Subtle modulations of the transcriptional activity induced by the AR have also been observed and frequently assigned to a polyglutamine stretch of variable length within the N-terminal domain of the receptor. This stretch is encoded by a variable number of CAG triplets in exon 1 of the AR gene located on the X chromosome. First observations of pathologically elongated AR CAG repeats in patients with X-linked spino-bulbar muscular atrophy showing marked hypoandrogenic traits were supplemented by partially conflicting findings of statistical significance also within the normal range of CAG repeat length: an involvement of prostate tissue, spermatogenesis, bone density, hair growth, cardiovascular risk factors and psychological factors has been demonstrated. The highly polymorphic nature of glutamine residues within the AR protein implies a subtle gradation of androgenicity among individuals within an environment of normal testosterone levels providing relevant ligand binding to ARs. This modulation of androgen effects may be small but continuously present during a man's lifetime and, hence, exerts effects that are measurable in many tissues as various degrees of androgenicity and represents a relevant effector of maleness. It remains to be elucidated whether these insights are important enough to become part of individually useful laboratory assessments. [source]

Bioenergetics in the pathogenesis of neurodegeneration

JOURNAL OF NEUROCHEMISTRY, Issue 2001
M. Flint Beal
Evidence implicating both mitochondria and bioenergetics as playing a crucial role in necrotic and apoptotic cell death is rapidly accumulating. Mitochondria are essential in controlling specific apoptosis cell death pathways and they are the major source of free radicals in the cell. Direct evidence for a role of mitochondria in neurodegenerative diseases comes from studies in Friedreich's Ataxia. Mutations in frataxin lead to an accumulation of iron within mitochondria. We found a three-fold increase in a marker of oxidative damage to DNA in the urine of patients with Friedreich's Ataxia. There is evidence for mitochondrial defects in patients with amyotrophic lateral sclerosis (ALS). There are mitochondrial abnormalities in liver biopsies and muscle biopsies from individuals with sporadic ALS. Muscle biopsies have shown reduced complex I activity in patients with sporadic ALS. A study of ALS cybrids showed a significant decrease in complex I activity as well as trends towards reduced complex 3 and 4 activities. We found increased levels of 8-hydroxy-2-deoxyguanosine, a marker of oxidative damage to DNA in the plasma, urine and CSF of sporadic ALS patients and increased numbers of point mutations in mtDNA of ALS spinal cord tissue. There is mitochondrial vacuolization in transgenic mouse models of ALS. We found substantial evidence for mitochondrial dysfunction in Huntington's Disease (HD). In HD postmortem brain tissue, there are significant reductions in complex 2, 3 activity. We also demonstrated increased brain lactate concentrations as well as reduced phosphocreatine to inorganic phosphate ratio in the resting muscle of patients with HD. More recent studies have demonstrated that there is abnormal depolarization of mitochondria of HD lymphoblasts, which directly correlates with CAG repeat length. There are reductions in ATP production in muscle are both presymptomatic and symptomatic HD patients. Transgenic mouse models of HD show significant reductions in N-acetylaspartate concentrations, which precede the onset of neuronal degeneration. We investigated a number of therapeutic interventions in both transgenic mouse models of ALS and HD. In transgenic ALS mice we found that oral administration of creatine dose-dependently extends survival and reduces the neuronal degeneration in the spinal cord. We found modest protection with ginkgo biloba and lipoic acid. In the HD mice we found significant improvement with oral administration of creatine in two different transgenic mouse models. Creatine not only extended survival but it also improved motor performance, delayed weight loss and attenuated striatal atrophy. Creatine significantly attenuated reductions in N-acetylaspartate concentrations as assessed using magnetic resonance spectroscopy. We also found significant neuroprotective effects with dichloroacetate, which stimulates pyruvate dehydrogenase. These findings implicate bioenergetic dysfunction in transgenic mouse models of both ALS and HD, and they suggest several novel therapeutic strategies aimed at energy replenishment. [source]

Automated binning of microsatellite alleles: problems and solutions

MOLECULAR ECOLOGY RESOURCES, Issue 1 2007
W. AMOS
Abstract As genotyping methods move ever closer to full automation, care must be taken to ensure that there is no equivalent rise in allele-calling error rates. One clear source of error lies with how raw allele lengths are converted into allele classes, a process referred to as binning. Standard automated approaches usually assume collinearity between expected and measured fragment length. Unfortunately, such collinearity is often only approximate, with the consequence that alleles do not conform to a perfect 2-, 3- or 4-base-pair periodicity. To account for these problems, we introduce a method that allows repeat units to be fractionally shorter or longer than their theoretical value. Tested on a large human data set, our algorithm performs well over a wide range of dinucleotide repeat loci. The size of the problem caused by sticking to whole numbers of bases is indicated by the fact that the effective repeat length was within 5% of the assumed length only 68.3% of the time. [source]

Performance measures in Friedreich ataxia: Potential utility as clinical outcome tools

MOVEMENT DISORDERS, Issue 7 2005
David R. Lynch MD
Abstract Although several neuroprotective agents have been proposed as potential therapies in Friedreich ataxia (FA), clinical trials of their efficacy are limited by a lack of sensitive outcome measures. We assessed whether performance measures (nine-hole peg test, the timed 25-foot walk, and low-contrast letter acuity) provide valid measures of disease status in FA. Scores for each measure correlated significantly with neurologic disability and disease duration. Rank correlations between scores for performance measures were moderate in magnitude, suggesting that the each test captures separate yet related dimensions of neurological function in FA. Linear regression models demonstrated that scores from the nine-hole peg test and the timed 25-foot walk (after reciprocal transformation) were predicted by age and triplet repeat length in patients with FA. In addition, comparison of the temporal courses of change for each performance measure demonstrated that scores from the timed 25-foot walk change early in the course of FA, nine-hole peg test scores change slowly over the full course of the disorder, and low-contrast letter acuity scores change in the later stages of the disease. Thus, a composite scale derived from these performance measures may provide the best overall measure for assessing disease progression throughout the illness. © 2005 Movement Disorder Society [source]

Androgen receptor CAG repeat length is not associated with the risk of incident symptomatic benign prostatic hyperplasia: Results from the prostate cancer prevention trial

THE PROSTATE, Issue 6 2010
Alan R. Kristal
Abstract BACKGROUND To examine whether androgen receptor (AR) CAG repeat length was associated with the risk of incident benign prostatic hyperplasia (BPH). METHODS A nested case-control study of 416 BPH cases and 527 controls drawn from Prostate Cancer Prevention Trial placebo-arm participants who were free of BPH at baseline. BPH was assessed over 7 years and was defined as receipt of medical or surgical treatment, two scores > 14 on the International Prostate Symptom Score (IPSS), or two increases in IPSS , 5 with at least one score , 12. RESULTS Compared to men with AR repeat length , 19, the covariate-adjusted odds ratios [95% CI] were 1.07 [0.73, 1.57] and 0.90 [0.55, 1.45]) for repeat length 20,24 and ,25, respectively. There was a weak association of AR repeat length with baseline serum testosterone (T) (Spearman r = 0.09, p < 0.02); however, control for or stratification by T did not change study results. Further, results did not differ when stratified by body mass index or baseline concentration of 3,-diol glucoronide, and were similar for all BPH definitions. CONCLUSIONS There were no associations of AR CAG repeat length and BPH risk. Knowledge of AR CAG repeat length provides no clinical useful information for the prevention of symptomatic BPH. Prostate 70: 584,590, 2010. © 2009 Wiley-Liss, Inc. [source]

The Relationship Between CAG Repeat Length and Age of Onset Differs for Huntington's Disease Patients with Juvenile Onset or Adult Onset

ANNALS OF HUMAN GENETICS, Issue 3 2007
J. Michael Andresen
Summary Age of onset for Huntington's disease (HD) varies inversely with the length of the disease-causing CAG repeat expansion in the HD gene. A simple exponential regression model yielded adjusted R-squared values of 0.728 in a large set of Venezuelan kindreds and 0.642 in a North American, European, and Australian sample (the HD MAPS cohort). We present evidence that a two-segment exponential regression curve provides a significantly better fit than the simple exponential regression. A plot of natural log-transformed age of onset against CAG repeat length reveals this segmental relationship. This two-segment exponential regression on age of onset data increases the adjusted R-squared values by 0.012 in the Venezuelan kindreds and by 0.035 in the HD MAPS cohort. Although the amount of additional variance explained by the segmental regression approach is modest, the two slopes of the two-segment regression are significantly different from each other in both the Venezuelan kindreds [F(2, 439) = 11.13, P= 2 × 10,5] and in the HD MAPS cohort [F(2, 688) = 38.27, P= 2 × 10,16]. In both populations, the influence of each CAG repeat on age of onset appears to be stronger in the adult-onset range of CAG repeats than in the juvenile-onset range. [source]

Huntington's disease,like 2 (HDL2) in North America and Japan

ANNALS OF NEUROLOGY, Issue 5 2004
Russell L. Margolis MD
Huntington's Disease,like 2 (HDL2) is a progressive, autosomal dominant, neurodegenerative disorder with marked clinical and pathological similarities to Huntington's disease (HD). The causal mutation is a CTG/CAG expansion mutation on chromosome 16q24.3, in a variably spliced exon of junctophilin-3. The frequency of HDL2 was determined in nine independent series of patients referred for HD testing or selected for the presence of an HD-like phenotype in North America or Japan. The repeat length, ancestry, and age of onset of all North American HDL2 cases were determined. The results show that HDL2 is very rare, with a frequency of 0 to 15% among patients in the nine case series with an HD-like presentation who do not have the HD mutation. HDL2 is predominantly, and perhaps exclusively, found in individuals of African ancestry. Repeat expansions ranged from 44 to 57 triplets, with length instability in maternal transmission detected in a repeat of 33 triplets. A younger age of onset is correlated with a longer repeat length (r2 = 0.29, p = 0.0098). The results further support the evidence that the repeat expansion at the chromosome 16q24.3 locus is the direct cause of HDL2 and provide preliminary guidelines for the genetic testing of patients with an HD-like phenotype. Ann Neurol 2004 An Erratum has been published for this article in Ann Neurol 56: 911, 2004. [source]

Heart Rate Variability Declines with Increasing Age and CTG Repeat Length in Patients with Myotonic Dystrophy Type 1

Chromatin dynamics of unfolding and refolding controlled by the nucleosome repeat length and the linker and core histones

BIOPOLYMERS, Issue 4 2007
Toshiro Kobori
Abstract Chromatin is composed of genomic DNA and histones, forming a hierarchical architecture in the nucleus. The chromatin hierarchy is common among eukaryotes despite different intrinsic properties of the genome. To investigate an effect of the differences in genome organization, chromatin unfolding processes were comparatively analyzed using Schizosaccaromyces pombe, Saccharomyces cerevisiae, and chicken erythrocyte. NaCl titration showed dynamic changes of the chromatin. 400,1000 mM NaCl facilitated beads with ,115 nm in diameter in S. pombe chromatin. A similar transition was also observed in S. cerevisiae chromatin. This process did not involve core histone dissociation from the chromatin, and the persistence length after the transition was ,26 nm for S. pombe and ,28 nm for S. cerevisiae, indicating a salt-induced unfolding to "beads-on-a-string" fibers. Reduced salt concentration recovered the original structure, suggesting that electrostatic interaction would regulate this discrete folding-unfolding process. On the other hand, the linker histone was extracted from chicken chromatin at 400 mM NaCl, and AFM observed the "beads-on-a-string" fibers around a nucleus. Unlike yeast chromatin, therefore, this unfolding was irreversible because of linker histone dissociation. These results indicate that the chromatin unfolding and refolding depend on the presence and absence of the linker histone, and the length of the linker DNA. © 2007 Wiley Periodicals, Inc. Biopolymers 85:295,307, 2007. This article was originally published online as an accepted preprint. The "Published Online" date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com [source]

Estimation of the age at onset in spinocerebellar ataxia type 2 Cuban patients by survival analysis

CLINICAL GENETICS, Issue 2 2010
LE Almaguer-Mederos
Almaguer-Mederosa LE, Falcón NS, Almira YR, Zaldivar YG, Almarales DC, Góngora EM, Herrera MP, Batallán KE, Armiñán RR, Manresa MV, Cruz GS, Laffita-Mesa J, Cyuz TM, Chang V, Auburger G, Gispert S, Pérez LV. Estimation of the age at onset in spinocerebellar ataxia type 2 Cuban patients by survival analysis. Previous studies have investigated the close association that exists between CAG repeat number and the age at onset in SCA2 = spinocerebellar ataxia type 2. These studies have focused on affected individuals. To further characterize this association and estimate the risk of a carrier developing SCA2 at a particular age as a function of a specific CAG repeat size, we have analyzed a large group of 924 individuals, including 394 presymptomatic and 530 affected individuals with a CAG repeat length of 32,79 units. Using a Kaplan,Meier survival analysis, we obtained cumulative probability curves for disease manifestation at a particular age for each CAG repeat length in the 34,45 range. These curves were significantly different (p < 0.001) and showed small overlap. All these information may be very valuable in predictive-testing programs, in the planning of studies for the identification of other genetic and environmental factors as modifiers of age at onset, and in the design of clinical trials for people at enlarged risk for SCA2. [source]

Androgen receptor gene polymorphism and the metabolic syndrome in 60,80 years old Norwegian men

FMR1 CGG Repeat Patterns and Flanking Haplotypes in Three Asian Populations and Their Relationship With Repeat Instability

ANNALS OF HUMAN GENETICS, Issue 6 2006
Youyou Zhou
Summary Hyper-expansion of a CGG repeat in the 5, untranslated region of the FMR1 gene followed by methylation and silencing is the predominant cause of Fragile X syndrome, the most common inherited mental retardation disorder. Most detailed studies of the FMR1 gene have focused on Caucasian populations and patients. We performed a detailed haplotype and linkage disequilibrium analysis of the FMR1 gene in a total of 454 unselected normal X chromosomes from three Asian populations, Chinese, Malay and Indian. Compared to Caucasians and African Americans, the diversity of normal FMR1 CGG repeat lengths, patterns and flanking haplotypes were lower in Asians. Strong linkage disequilibrium was observed between the CGG repeat and flanking FMR1 markers in all three Asian populations, with strong association between specific CGG repeat alleles and flanking marker alleles observed only in the Chinese and Malays. A test for randomness of distribution between FRAXA CGG repeat patterns and flanking FMR1 marker haplotypes also revealed a highly significant non-random distribution between CGG repeat patterns and flanking haplotypes in all three ethnic groups (P < 0.001). Extending previous findings in Caucasians and African Americans we present a novel statistical approach, using data from unselected population samples alone, to show an association between absence of at least one AGG interruption in any position (5,, 3,, or middle) and increased CGG repeat instability. [source]