Faculty Research and Publications
Permanent URI for this collectionhttps://digital.lib.washington.edu/handle/1773/27329
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Item type: Item , The paternal age at conception effect on offspring telomere length: mechanistic, comparative and adaptive perspectives(Philosophical Transactions B, 2017-10) Eisenberg, Dan T. A.; Kuzawa, Christopher W.Telomeres are repeating DNA found at the ends of chromosomes that, in the absence of restorative processes, shorten with cell replications and are implicated as a cause of senescence. It appears that sperm telomere length (TL) increases with age in humans, and as a result offspring of older fathers inherit longer telomeres. We review possible mechanisms underlying this paternal age at conception (PAC) effect on TL, including sperm telomere extension due to telomerase activity, age-dependent changes in the spermatogonial stem cell population (possibly driven by ‘selfish’ spermatogonia) and non-causal confounding. In contrast to the lengthening of TL with PAC, higher maternal age at conception appears to predict shorter offspring TL in humans. We review evidence for heterogeneity across species in the PAC effect on TL, which could relate to differences in statistical power, sperm production rates or testicular telomerase activity. Finally, we review the hypothesis that the PAC effect on TL may allow a gradual multi-generational adaptive calibration of maintenance effort, and reproductive lifespan, to local demographic conditions: descendants of males who reproduced at a later age are likely to find themselves in an environment where increased maintenance effort, allowing later reproduction, represents a fitness improving resource allocation.Item type: Item , Raw data for demographic analyses of the Willie and Martin Handcart Companies(2016-01) Grayson, Donald K.Raw data for demographic analyses of the Willie and Martin Handcart CompaniesItem type: Item , Improving qPCR telomere length assays: Controlling for well position effects increases statistical power(American Journal of Human Biology, 2015-01) Eisenberg, Dan T. A.; Kuzawa, Christopher W.; Hayes, M. GeoffreyObjectives: Telomere length (TL) is commonly measured using quantitative PCR (qPCR). Although easier than the southern blot of terminal restriction fragments (TRF) TL measurement method, one drawback of qPCR is that it introduces greater measurement error and thus reduces the statistical power of analyses. To address a potential source of measurement error, we consider the effect of well position on qPCR TL measurements. Methods: qPCR TL data from 3,638 people run on a Bio-Rad iCycler iQ are reanalyzed here. To evaluate measurement validity, correspondence with TRF, age and between mother and offspring are examined. Results: First, we present evidence for systematic variation in qPCR TL measurements in relation to thermocycler well position. Controlling for these well-position effects consistently improves measurement validity and yields estimated improvements in statistical power equivalent to increasing sample sizes by 16%. We additionally evaluated the linearity of the relationships between telomere and single copy gene control amplicons and between qPCR and TRF measures. We find that, unlike some previous reports, our data exhibit linear relationships. We introduce the standard error in percent, a superior method for quantifying measurement error compared to the commonly used coefficient of variation. Using this measure, we find that excluding samples with high measurement error does not improve measurement validity. Conclusions: Future studies using block-based thermocyclers should consider well position effects. Since additional information can be gleaned from well position corrections, re-running analyses of previous results with well position correction could serve as an independent test of the validity of these results.