Search

Abstract: Objectives: Telomere length (TL) is a biomarker of aging and age‐related decline. Although venous blood is considered the “gold standard” for TL measurement, its collection is often not feasible or desired in nonclinical settings. Saliva and dried blood spots (DBS) have been used as alternatives when venipuncture cannot be performed. However, it is not known whether these sample types yield TL measurements comparable to those obtained from venous blood. We sought to determine whether different samples from the same individual yield comparable TL measurements. Methods: We extracted DNA from matched buffy coat, saliva (Oragene and Oasis), and DBS (venous and capillary) samples from 40 women aged 18‐77 years. We used the monochrome multiplex qPCR (MMQPCR) assay to measure TL in all sample types for each participant and applied quality control measures to retain only high‐quality samples for analysis. We then compared TL from buffy coat and saliva to examine how these measurements differ and to test if TL is correlated across sample types. Results: TL differed significantly across buffy coat, Oragene saliva, and Oasis saliva samples. TL from buffy coat and Oragene saliva was moderately correlated (ρ = 0.48, P = .002) and the most similar in size. Oasis saliva TL was not correlated with buffy coat or Oragene saliva TL, and was the shortest. DBS DNA yields were inadequate for TL measurement using the MMQPCR assay. Conclusions: Using a matched dataset we demonstrate that sample type significantly influences the TL measurement obtained using the MMQPCR assay. [ABSTRACT FROM AUTHOR]

Few studies have combined genetic association analyses with functional characterization of infection-associated SNPs in natural populations of nonhuman primates. Here, we investigate the relationship between host genetic variation, parasitism and natural selection in a population of red colobus ( Procolobus rufomitratus tephrosceles) in Kibale National Park, Uganda. We collected parasitological, cellular and genomic data to test the following hypotheses: (i) MHC- DQA1 regulatory genetic variation is associated with control of whipworm ( Trichuris) infection in a natural population of red colobus; (ii) infection-associated SNPs are functional in driving differential gene expression in vitro; and (iii) balancing selection has shaped patterns of variation in the MHC- DQA1 promoter. We identified two SNPs in the MHC- DQA1 promoter, both in transcription factor binding sites, and both of which are associated with decreased control of Trichuris infection. We characterized the function of both SNPs by testing differences in gene expression between the two alleles of each SNP in two mammalian cell lines. Alleles of one of the SNPs drove differential gene expression in both cell lines, while the other SNP drove differences in expression in one of the cell lines. Additionally, we found evidence of balancing selection acting on the MHC- DQA1 promoter, including extensive trans-species polymorphisms between red colobus and other primates, and an excess of intermediate-frequency alleles relative to genome-wide, coding and noncoding RADseq data. Our data suggest that balancing selection provides adaptive regulatory flexibility that outweighs the consequences of increased parasite infection intensity in heterozygotes. [ABSTRACT FROM AUTHOR]

ABSTRACT The human brain and human cognitive abilities are strikingly different from those of other great apes despite relatively modest genome sequence divergence. However, little is presently known about the interspecies divergence in gene structure and transcription that might contribute to these phenotypic differences. To date, most comparative studies of gene structure in the brain have examined humans, chimpanzees, and macaque monkeys. To add to this body of knowledge, we analyze here the brain transcriptome of the western lowland gorilla ( Gorilla gorilla gorilla), an African great ape species that is phylogenetically closely related to humans, but with a brain that is approximately one-third the size. Manual transcriptome curation from a sample of the planum temporale region of the neocortex revealed 12 protein-coding genes and one noncoding-RNA gene with exons in the gorilla unmatched by public transcriptome data from the orthologous human loci. These interspecies gene structure differences accounted for a total of 134 amino acids in proteins found in the gorilla that were absent from protein products of the orthologous human genes. Proteins varying in structure between human and gorilla were involved in immunity and energy metabolism, suggesting their relevance to phenotypic differences. This gorilla neocortical transcriptome comprises an empirical, not homology- or prediction-driven, resource for orthologous gene comparisons between human and gorilla. These findings provide a unique repository of the sequences and structures of thousands of genes transcribed in the gorilla brain, pointing to candidate genes that may contribute to the traits distinguishing humans from other closely related great apes. J. Comp. Neurol. 524:288-308, 2016. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Objectives The obesity epidemic in Mexico is increasing and represents a considerable public health challenge. The population aged 50 years and older is also increasing and is not exempt from the obesity rise. We aimed to determine the current prevalence of Body Mass Index (BMI) categories in a sample of Mexicans aged 50 years and older and to test the associations of BMI with physical activity categories and related factors. Methods Data from 2,032 individuals aged 50 years and older who participated in SAGE Wave 1 (2009-2010) were analyzed. Representativeness of the sample was obtained by using weighted data. Descriptive statistics, chi square tests, simple regression analysis, and multiple regression analysis were performed in relation to BMI, self-reported physical activity categories, and several variables, including demographic characteristics and selected risk factors for non-communicable diseases. Results Among older adults, 0.6% was found to be underweight, 21.4% normal weight, 49.4% overweight, and 28.7% obese. It was also found that practicing vigorous intensity physical activity (−1.32) and being 80 years or older (−2.73) were significantly associated ( P < 0.05) with a lower mean BMI (28.3). In contrast, being in the lowest income quintile (1.35), and living in urban areas (0.86) were significantly associated with a higher mean BMI. Conclusions The study results contribute to the current understanding of obesity etiology in Mexico, and moreover confirm that overweight and obesity are current public health problems that must be addressed in specific subgroups of older adults. Am. J. Hum. Biol. 27:326-333, 2015. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Objectives Human brain development follows a unique pattern characterized by a prolonged period of postnatal growth and reorganization, and a postnatal peak in glucose utilization. The molecular processes underlying these developmental changes are poorly characterized. The objectives of this study were to determine developmental trajectories of gene expression and to examine the evolutionary history of genes differentially expressed as a function of age. Methods We used microarrays to determine age-related patterns of mRNA expression in human cerebral cortical samples ranging from infancy to adulthood. In contrast to previous developmental gene expression studies of human neocortex that relied on postmortem tissue, we measured mRNA expression from the nondiseased margins of surgically resected tissue. We used regression models designed to identify transcripts that followed significant linear or curvilinear functions of age and used population genetics techniques to examine the evolution of these genes. Results We identified 40 transcripts with significant age-related trajectories in expression. Ten genes have documented roles in nervous system development and energy metabolism, others are novel candidates in brain development. Sixteen transcripts showed similar patterns of expression, characterized by decreasing expression during childhood. Comparative genomic analyses revealed that the regulatory regions of three genes have evidence of adaptive evolution in recent human evolution. Conclusions These findings provide evidence that a subset of genes expressed in the human cerebral cortex broadly mirror developmental patterns of cortical glucose consumption. Whether there is a causal relationship between gene expression and glucose utilization remains to be determined. Am. J. Hum. Biol. 25:418-430, 2013. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Adrenarche is a developmental event involving differentiation of the adrenal gland and production of adrenal androgens, and has been hypothesized to play a role in the extension of the preadolescent phase of human ontogeny. It remains unclear whether any nonhuman primate species shows a similar suite of endocrine, biochemical, and morphological changes as are encompassed by human adrenarche. Here, we report serum concentrations of the adrenal androgens dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) measured in 698 cross-sectional and mixed longitudinal serum samples from catarrhine primates ranging from 0.6 to 47 years of age. DHEAS in Pan is most similar to that of humans in both age-related pattern and absolute levels, and a transient early increase appears to be present in Gorilla. DHEA levels are highest in Cercocebus, Cercopithecus, and Macaca. We also tested for evidence of adaptive evolution in six genes that code for proteins involved in DHEA/S synthesis. Our genetic analyses demonstrate the protein-coding regions of these genes are highly conserved among sampled primates. We describe a tandem gene duplication event probably mediated by a retrotransposon that resulted in two 3-β-hydroxysteroid dehydrogenase/Delta 5-Delta 4 genes ( HSD3B1 and HSD3B2) with tissue specific functions in catarrhines. In humans, HSD3B2 is expressed primarily in the adrenals, ovary, and testis, while HSD3B1 is expressed in the placenta. Taken together, our findings suggest that while adrenarche has been suggested to be unique to hominoids, the evolutionary roots for this developmental stage are more ancient. Am J Phys Anthropol, 2012. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]