112 research outputs found
Neon: An R Package to Estimate Human Effective Population Size and Divergence Time from Patterns of Linkage Disequilibrium between {SNPS}
No full textInsights into gene tissue specificity and protein-protein interactions in the context of purifying selection in humans
No full textBackground: How much are natural selection and gene characteristics, such as the number of protein-protein interactions (PPIs), tissue specificity (τ), and expression level, connected? Methods: In order to investigate these relationships, we combined different metrics linked to genetic constraints and analyzed their distribution concerning PPIs, τ and expression levels. Results: We discovered a positive correlation between genetic constraints, PPIs, and expression levels in all tissues. On the other hand, we obtained a negative correlation between genetic constraints and τ. Furthermore, the fraction of variance in PPI and τ explained by the constraints metrics is around 6% and 10%, respectively. Conclusions: We observed that the variance of expression of tissue-specific genes seems not related to their level of selection constraints, which is the opposite of what is found on non-tissue-specific genes. Overall these observations would help to elucidate the relationship between natural selection and gene features
Gone with the currents: lack of genetic differentiation at the circum-continental scale in the Antarctic krill <it>Euphausia superba</it>
No full textAbstract Background Southern Ocean fauna represent a significant amount of global biodiversity, whose origin may be linked to glacial cycles determining local extinction/eradication with ice advance, survival of refugee populations and post-glacial re-colonization. This pattern implies high potential for differentiation in benthic shelf species with limited dispersal, yet consequences for pelagic organisms are less clear. The present study investigates levels of genetic variation and population structure of the Antarctic krill Euphausia superba using mitochondrial DNA and EST-linked microsatellite markers for an unprecedentedly comprehensive sampling of its populations over a circum-Antarctic range. Results MtDNA (ND1) sequences and EST-linked microsatellite markers indicated no clear sign of genetic structure among populations over large geographic scales, despite considerable power to detect differences inferred from forward-time simulations. Based on ND1, few instances of genetic heterogeneity, not significant after correction for multiple tests, were detected between geographic or temporal samples. Neutrality tests and mismatch distribution based on mtDNA sequences revealed strong evidence of past population expansion. Significant positive values of the parameter g (a measure of population growth) were obtained from microsatellite markers using a coalescent-based genealogical method and suggested a recent start (60 000 - 40 000 years ago) for the expansion. Conclusions The results provide evidence of lack of genetic heterogeneity of Antarctic krill at large geographic scales and unequivocal support for recent population expansion. Lack of genetic structuring likely reflects the tight link between krill and circum-Antarctic ocean currents and is consistent with the hypothesis that differentiation processes in Antarctic species are largely influenced by dispersal potential, whereas small-scale spatial and temporal differentiation might be due to local conditions leading to genetic patchiness. The signal of recent population growth suggests differential impact of glacial cycles on pelagic Antarctic species, which experienced population expansion during glaciations with increased available habitat, versus sedentary benthic shelf species. EST-linked microsatellites provide new perspectives to complement the results based on mtDNA and suggest that data-mining of EST libraries will be a useful approach to facilitate use of microsatellites for additional species.</p
A “population-based approach” to study the link between TAS2R genes, taste perception and food liking.
No full textVariations at the TAS2R38 gene account for the major portion of differences in PROP (6-n-propylthiouracil) taste perception, which have been shown to influence food preferences and dietary behaviour. We examined the link between PROP taste responses, food preferences and TAS2R genes in six different populations of the Caucasus and Central Asia, located along the Silk Road. We reported, for the first time, genotypic frequencies of the TAS2R38 gene and PROP phenotype distribution in these populations. We found a strong relationship between PROP tasting and food preferences (r=0.67, p-value=0.009) using a “population-based approach”, in which we exploit phenotypic differences between populations comparing a distance matrix based on PROP taste responses and a matrix based on food preferences. No evidence of correlation was found between the distance matrix of food preference and the matrix of genetic distance based on TAS2R38 or the matrix based on the whole genome. Preliminary results of candidate gene analysis allowed us to identify others TAS2R genes that could cooperate with TAS2R38 in the modulation of PROP perception and as consequence food liking.
Besides increasing the knowledge of worldwide TAS2R38 prevalences and bitter taste, our results show that differences in food preferences among populations correlate with PROP status but not with the TAS2R38 gene, suggesting that PROP status is probably a marker for general taste sensitivity and as such is a major driver of food preferences. In addition, our work represent a starting point to study the involvement of multiple genes in bitter perception and food liking
MMAB, a novel candidate gene to be screened in the molecular diagnosis of Mevalonate Kinase Deficiency
No full textMevalonate kinase deficiency (MKD) is an autosomal recessive inflammatory disease. Mutations in MVK gene are associated
with MKD with modest genotype–phenotype correlation. In spite of recent guidelines indicating specific MVK mutations for
the more severe form or the milder one, little is known about MVK variability within and between populations. The aim of
this work is to provide supplementary information about MVK variability useful in the molecular diagnosis of MKD, as well
as to unravel the presence of novel genes potentially involved as involved in the clinical heterogeneity of MKD phenotype.
We used a population-based approach, coupled with Combined Annotation–Dependent Depletion (CADD) score, to analyze
the level of genetic variability for common and putatively deleterious MVK variants. We also performed Exome screening
with the Illumina Human Exome Bead Chip on 21 MKD patients to double-check our in silico findings. Haplotype block
detection in different populations revealed the existence of two blocks in MVK; interestingly, the first haploblock comprises
the promoter region shared with MMAB gene. Analyses of MMAB and MVK genetic variants in 21 MKD patients strengthen
our observations showing a novel scenario in which the same mutations commonly associated with MKD are found coupled
with different combination of MMAB rs7134594 SNP was already described as associated with HDL cholesterol level and
present in the haploblock promoter region. The rs7134594 SNP is reported as an eQTL for MVK and MMAB. Hypothesizing
the presence of genetic variants modulating the complex phenotypic spectrum of MKD, we suggest that future directions in
screening for MKD pathogenic variants should focus both MMAB and MVK genes
Author Correction: Establishment and equilibrium levels of deleterious mutations in large populations (Scientific Reports, (2019), 9, 1, (10384), 10.1038/s41598-019-46803-7)
No full textThe original version of this Article contained errors. Affiliations 1 and 2 were reversed. Secondly, Affiliation 7 was incorrectly given as ‘Institute for Cellular and Molecular Medicine, Department of Immunology, and SAMRC Extramural Unit for Stem Cell Research and Therapy, Faculty of Health Sciences, University of Pretoria, Pretoria, 0084, South Africa’. Thirdly, an affiliation was omitted for the author Michael S. Pepper, which is now listed as Affiliation 8. Fourthly, Affiliation 1 was omitted for the author Johan W. Viljoen. Finally, Augustinus J. van Zyl was incorrectly affiliated with ‘Institute for Maternal and Child Health, IRCCS ‘Burlo Garofolo’, Trieste, Italy.’ The correct author affiliations are listed below: Affiliation 1: Department of Electrical, Electronic and Computer Engineering, EBIT, University of Pretoria, Pretoria 0028, South Africa Johan W. Viljoen and J. Pieter de Villiers Affiliation 2: Development, Research and Technology Department, Hensoldt Optronics, Centu..
GBRAP: A Comprehensive Database and Tool for Exploring Genomic Diversity Across All Domains of Life
No full textEvolutionary studies require extensive examination of genomic information across all domains of life. Despite the availability of a large number of genomes through GenBank, the effective visualization or comparison of the information they contain is challenging due to many reasons, including their size. We introduce genome-based retrieval and analysis parser, a comprehensive software tool to analyze genome files, and an online database housing an extensive collection of carefully curated, high-quality genome statistics for all the organisms available in the RefSeq database of National Center for Biotechnology Information. Users can either directly search, or select from precategorized groups, the organisms of their choice and retrieve data, and the output is generated as tables containing more than 200 columns of useful genomic information (base counts, GC content, Shannon entropy, codon usage, etc.) separately calculated for different genomic elements (e.g. coding sequences, introns, transfer RNA, ribosomal RNA, noncoding RNA, etc.). The data are independently displayed (if applicable) for each chromosomal, mitochondrial, plastid, or plasmid sequence. All the data can be visualized on the database or downloaded as comma-separated value or Excel files. The genome-based retrieval and analysis parser database is free to access without any registration and is publicly available at http://tacclab.org/gbrap
Insight into genetic determinants of resting heart rate
No full textBackground
Recent studies suggested that resting heart rate (RHR) might be an independent predictor of cardiovascular mortality and morbidity. Nonetheless, the interrelation between RHR and cardiovascular diseases is not clear. In order to resolve this puzzle, the importance of genetic determinants of RHR has been recently suggested, but it needs to be further investigated.
Objective
The aim of this study was to estimate the contribution of common genetic variations on RHR using Genome Wide Association Study.
Methods
We performed a Genome Wide Association Study in an isolated population cohort of 1737 individuals, the Italian Network on Genetic Isolates — Friuli Venezia Giulia (INGI-FVG). Moreover, a haplotype analysis was performed. A regression tree analysis was run to highlight the effect of each haplotype combination on the phenotype.
Results
A significant level of association (p < 5 × 10− 8) was detected for Single Nucleotide Polymorphisms (SNPs) in two genes expressed in the heart: MAML1 and CANX. Founding that the three different variants of the haplotype, which encompass both genes, yielded a phenotypic correlation. Indeed, a haplotype in homozygosity is significantly associated with the lower quartile of RHR (RHR ≤ 58 bpm). Moreover no significant association was found between cardiovascular risk factors and the different haplotype combinations.
Conclusion
Mastermind-like 1 and Calnexin were found to be associated with RHR. We demonstrated a relation between a haplotype and the lower quartile of RHR in our populations. Our findings highlight that genetic determinants of RHR may be implicated in determining cardiovascular diseases and could allow a better risk stratification
Investigation of the link between PROP taste perception and vegetables consumption using FAOSTAT data
No full textIn this work we investigated, in populations located in Central Asia, the relationship between PROP taste perception and vegetables liking and consumption using FAOSTAT dataset. Collected data were analysed using distance matrices, Mantel test and Pearson correlation. Populations showing similar ability in tasting PROP bitterness are more similar as respect to vegetable consumption (r = 0.63, p-value = .05). Moreover, a significant negative correlation was found between the percentage of Non Taster (NT) in different countries and the percentage of vegetable consumption (r = -0.87, p-value = .02), while a significant positive correlation emerged between the percentage of Super Taster (ST) and the percentage of vegetable liking (r = 0.87, p-value = .02). In our work we showed that differences in bitter perception among populations contributes to differences in vegetable liking and vegetable consumption. More in detail, populations with higher percentage of ST consume more vegetables than population where the majority of individuals are NT
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