scholarly journals Telomere Length and Bipolar Disorder

2017 ◽  
Vol 43 (2) ◽  
pp. 445-453 ◽  
Author(s):  
Timothy R Powell ◽  
Danai Dima ◽  
Sophia Frangou ◽  
Gerome Breen
Keyword(s):  
Bipolar Disorder ◽  
Telomere Length ◽  
Memory Function ◽  
Familial Risk ◽  
Single Copy ◽  
Hippocampal Volume ◽  
Ratio Method ◽  
Paired Associates ◽  
Psychiatric Status ◽  
Telomere Sequence

AbstractVariation in telomere length is heritable and is currently considered a promising biomarker of susceptibility for neuropsychiatric disorders, particularly because of its association with memory function and hippocampal morphology. Here, we investigate telomere length in connection to familial risk and disease expression in bipolar disorder (BD). We used quantitative PCRs and a telomere-sequence to single-copy-gene-sequence ratio method to determine telomere length in genomic DNA extracted from buccal smears from 63 patients with BD, 74 first-degree relatives (49 relatives had no lifetime psychopathology and 25 had a non-BD mood disorder), and 80 unrelated healthy individuals. Participants also underwent magnetic resonance imaging to determine hippocampal volumes and cognitive assessment to evaluate episodic memory using the verbal paired associates test. Telomere length was shorter in psychiatrically well relatives (p=0.007) compared with unrelated healthy participants. Telomere length was also shorter in relatives (regardless of psychiatric status;p<0.01) and patients with BD not on lithium (p=0.02) compared with lithium-treated patients with BD. In the entire sample, telomere length was positively associated with left and right hippocampal volume and with delayed recall. This study provides evidence that shortened telomere length is associated with familial risk for BD. Lithium may have neuroprotective properties that require further investigation using prospective designs.

scholarly journals A Synthetic Single-Stranded Dual-Template Oligonucleotide as a Reference Standard for Monochrome Multiplex qPCR Measurements of Average Telomere Length

2020 ◽  
Author(s):  
Richard M. Cawthon
Keyword(s):  
Telomere Length ◽  
Quantitative Pcr ◽  
Single Copy ◽  
Repeat Sequence ◽  
Experimental Sample ◽  
Single Copy Gene ◽  
Reference Standard ◽  
Standard Curve ◽  
Telomere Sequence ◽  
Copy Gene

ABSTRACTQuantitative PCR is frequently used to measure average telomere length (TL) relative to the TL of a reference DNA sample of the investigator’s choosing. This makes comparisons of TLs across studies and laboratories difficult. Here we demonstrate that a single synthetic single-stranded dual-template oligonucleotide (DTO) containing both a telomere repeat sequence (T) and a segment of the human beta-globin (HBB) single copy gene (S) can be used as a universal reference standard for monochrome multiplex quantitative PCR (MMqPCR) measurements of average TL using SYBR Green I as the only fluorescent reporter dye. A set of twelve concentrations of the DTO is prepared by serial 3-fold dilutions, to a lowest concentration of ~20 copies per μl. The 5 highest concentrations are used for the T standard curve, and the 5 lowest concentrations are used for the S standard curve. For each reaction 5 μl containing approximately 3 ng of genomic DNA (or one of the DTO dilutions) is mixed with 5 μl of a 2x MasterMix containing the primers for T and S amplification, and MMqPCR is performed. The design of the primers and thermal cycling profile allows all T amplification signals to be collected before exponential amplification of the S signal begins. Exponential amplification from S is then carried out in a temperature range that keeps the telomere product fully melted and therefore unable to influence the S amplification signal. The T value for each DNA sample is the Standard Curve DTO dilution that contains the same number of copies of the telomere sequence as the experimental sample, and the S value is the DTO dilution that contains the same number of copies of the single copy gene sequence as the experimental sample. Dividing the first dilution by the second dilution yields an absolute T/S ratio, since it is expressed relative to the fixed 1:1 T/S ratio that is built into the DTO by design. Absolute T/S ratios for average TL in 48 human DNA samples determined by this method correlated strongly with mean Terminal Restriction Fragment (mTRF) lengths for the same DNA samples determined by the Southern Blot method (R-squared = 0.801). This DTO and the accompanying protocol may facilitate the standardization of average telomere length measurements and analyses across laboratories.

scholarly journals Telomere Length as a Biomarker for Race-Related Health Disparities

Genes ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 78
Author(s):  
Vaithinathan Selvaraju ◽  
Megan Phillips ◽  
Anna Fouty ◽  
Jeganathan Ramesh Babu ◽  
Thangiah Geetha
Keyword(s):  
Blood Pressure ◽  
Telomere Length ◽  
Diastolic Pressure ◽  
Systolic Pressure ◽  
Single Copy ◽  
Normal Weight ◽  
Length Ratio ◽  
Hierarchical Regression ◽  
Significant Difference ◽  
The Usa

Disparities between the races have been well documented in health and disease in the USA. Recent studies show that telomere length, a marker of aging, is associated with obesity and obesity-related diseases, such as heart disease and diabetes. The current study aimed to evaluate the connection between telomere length ratio, blood pressure, and childhood obesity. The telomere length ratio was measured in 127 children from both European American (EA) and African American (AA) children, aged 6–10 years old. AA children had a significantly high relative telomere to the single copy gene (T/S) ratio compared to EA children. There was no significant difference in the T/S ratio between normal weight (NW) and overweight/obese (OW/OB) groups of either race. Blood pressure was significantly elevated in AA children with respect to EA children. Hierarchical regression analysis adjusted for race, gender, and age expressed a significant relationship between the T/S ratio and diastolic pressure. Low T/S ratio participants showed a significant increase in systolic pressure, while a high T/S ratio group showed an increase in diastolic pressure and heart rate of AA children. In conclusion, our findings show that AA children have high T/S ratio compared to EA children. The high T/S ratio is negatively associated with diastolic pressure.

scholarly journals A pooled sequencing approach identifies a candidate meiotic driver in Drosophila

2017 ◽  
Author(s):  
Kevin H-C Wei ◽  
Hemakumar M. Reddy ◽  
Chandramouli Rathnam ◽  
Jimin Lee ◽  
Deanna Lin ◽  
...  
Keyword(s):  
Telomere Length ◽  
Natural Populations ◽  
Meiotic Drive ◽  
Length Variation ◽  
Sequence Evolution ◽  
Nucleotide Polymorphisms ◽  
Mendelian Segregation ◽  
Transmission Frequency ◽  
Multiple Observations ◽  
Telomere Sequence

AbstractMeiotic drive occurs when a selfish element increases its transmission frequency above the Mendelian ratio by hijacking the asymmetric divisions of female meiosis. Meiotic drive causes genomic conflict and potentially has a major impact on genome evolution, but only a few drive loci of large effect have been described. New methods to reliably detect meiotic drive are therefore needed, particularly for discovering moderate-strength drivers that are likely to be more prevalent in natural populations than strong drivers. Here we report an efficient method that uses sequencing of large pools of backcross (BC1) progeny to test for deviations from Mendelian segregation genome-wide of single-nucleotide polymorphisms (SNPs) that distinguish the parental strains. We show that meiotic drive can be detected by a characteristic pattern of decay in distortion of SNP frequencies, caused by recombination unlinking the driver from distal loci. We further show that control crosses allow allele-frequency distortion caused by meiotic drive to be distinguished from distortion resulting from developmental effects. We used this approach to test whether chromosomes with extreme telomere-length differences segregate at Mendelian ratios, as telomeric regions are a potential hotspot for meiotic drive due to their roles in meiotic segregation and multiple observations of high rates of telomere sequence evolution. Using four different pairings of long and short telomere strains, we find no evidence that extreme telomere-length variation causes meiotic drive in Drosophila. However, we identify one candidate meiotic driver in a centromere-linked region that shows an ~8% increase in transmission frequency, corresponding to a ~54:46 segregation ratio. Our results show that candidate meiotic drivers of moderate strength can be readily detected and localized in pools of F1 progeny.

scholarly journals Multiple sclerosis and psychiatric disorders: Comorbidity and sibling risk in a nationwide Swedish cohort

2014 ◽  
Vol 20 (14) ◽  
pp. 1881-1891 ◽  
Author(s):  
Viktoria Johansson ◽  
Cecilia Lundholm ◽  
Jan Hillert ◽  
Thomas Masterman ◽  
Paul Lichtenstein ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Bipolar Disorder ◽  
Psychiatric Disorders ◽  
Psychiatric Patients ◽  
Familial Risk ◽  
Positive Association ◽  
Protective Mechanisms ◽  
Genetic Liability ◽  
Sibling Comparison ◽  
National Patient

Background: Psychiatric disorders are known to be prevalent in multiple sclerosis (MS). Objective: The objective of this paper is to study comorbidity between MS and bipolar disorder, schizophrenia and depression in a nationwide cohort and to determine whether shared genetic liability underlies the putative association. Methods: We identified ICD-diagnosed patients with MS ( n = 16,467), bipolar disorder ( n = 30,761), schizophrenia ( n = 22,781) and depression ( n = 172,479) in the Swedish National Patient Register and identified their siblings in the Multi-Generation Register. The risk of MS was compared in psychiatric patients and in matched unexposed individuals. Shared familial risk between MS and psychiatric disorders was estimated by sibling comparison. Results: The risk of MS was increased in patients with bipolar disorder (hazard ratio (HR) 1.8, 95% confidence interval (CI) 1.6–2.2, p < 0.0001) and depression (HR 1.9, 95% CI 1.7–2.0, p < 0.0001). MS risk in schizophrenia was decreased (HR 0.6, 95% CI 0.4–0.9, p = 0.005). The association between having a sibling with a psychiatric disorder and developing MS was not significant. Conclusion: We found a strong positive association between MS and bipolar disorder and depression that could not be explained by genetic liability. The unexpected negative association between MS and schizophrenia might be spurious or indicate possible protective mechanisms that warrant further exploration.

scholarly journals Relationship Between Leukocyte Telomere Length, Telomerase Activity, and Hippocampal Volume in Early Aging

2014 ◽  
Vol 71 (7) ◽  
pp. 921 ◽  
Author(s):  
Emily G. Jacobs ◽  
Elissa S. Epel ◽  
Jue Lin ◽  
Elizabeth H. Blackburn ◽  
Natalie L. Rasgon
Keyword(s):  
Telomere Length ◽  
Hippocampal Volume ◽  
Telomerase Activity ◽  
Leukocyte Telomere Length ◽  
Early Aging

Leukocyte telomere length in patients with bipolar disorder: An updated meta-analysis and subgroup analysis by mood status

2018 ◽  
Vol 270 ◽  
pp. 41-49 ◽  
Author(s):  
Yu-Chi Huang ◽  
Liang-Jen Wang ◽  
Ping-Tao Tseng ◽  
Chi-Fa Hung ◽  
Pao-Yen Lin
Keyword(s):  
Bipolar Disorder ◽  
Telomere Length ◽  
Subgroup Analysis ◽  
Meta Analysis ◽  
Leukocyte Telomere Length

scholarly journals 208. Behavioral and Neural Sustained Attention Deficits in Bipolar Disorder and Familial Risk of Bipolar Disorder

2018 ◽  
Vol 83 (9) ◽  
pp. S84 ◽  
Author(s):  
David Pagliaccio ◽  
Jillian Wiggins ◽  
Nancy Adleman ◽  
Elizabeth Harkins ◽  
Alexa Curhan ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Sustained Attention ◽  
Familial Risk ◽  
Attention Deficits

Abstract 278: Diet-Induced Leukocyte Telomere Shortening Correlates with Extent of Atherosclerosis

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
GENESIO KARERE ◽  
Shifra Birnbaum ◽  
Clint Christensen ◽  
Michael Mahaney ◽  
John VandeBerg ◽  
...  
Keyword(s):  
Telomere Length ◽  
Pearson Correlation ◽  
Single Copy ◽  
Developed Countries ◽  
Primate Model ◽  
Telomere Shortening ◽  
Atherosclerotic Lesions ◽  
Potential Biomarker ◽  
Significant Difference ◽  
Before And After

Introduction: Cardiovascular disease, the leading cause of death in developed countries, is commonly due to atherosclerosis. Studies have demonstrated association between leukocyte telomere shortening (LTS), extent of atherosclerotic lesions and accelerated cell senescence. Further LTS is associated with dietary intake. However, efforts to link LTS, diet and extent of lesions have been unsuccessful in humans due to difficulties controlling diet in large human population studies. To begin addressing these critical issues, we controlled dietary fat (high-fat, HF) in baboons for 2yrs - a well-developed primate model of human atherosclerosis. This is the first study in primates showing correlation of LTS with both chronic HF diet and atherosclerotic lesions. Hypothesis: We hypothesized that leukocyte telomere length decreased with chronic HF diet in baboons and is correlated with extent of atherosclerotic lesions. Methods and Results: A cohort of pedigreed baboons (n=107; females=46, males=61) was fed a HF diet for 2yrs. Absolute leukocyte telomere lengths (LTL; kb/diploid genome) were quantified by qPCR before and after diet challenge. Total telomere length was calculated by computing the ratio of telomere quantity per single copy gene quantity (baboon LIPG). Mean LTL was significantly shorter after feeding baboons a HF diet for 2 yrs (paired t test, p=0.03). Baboons (n=232) maintained on a low fat diet for 2yrs showed no significant difference in LTL (p=0.47). These findings suggest that a HF diet accelerates LTS. Further we quantified the extent of atherosclerotic lesions in baboons after 2yr HF diet and found that LTL, adjusted for age and sex, were correlated with lesions in descending aorta (Pearson correlation, r=0.19; p=0.03). Interestingly this correlation was significant in females but not in males after adjusting for age (r=0.27, p=0.03). Conclusions: LTS correlates with chronic feeding with a HF diet in baboons, is significantly correlated with arterial lesions and the correlation is sex-specific. These findings suggest that LTS may be a potential biomarker of extent of atherosclerosis.

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