Influence of selection on the probability of fixation at a locus with multiple alleles.

Background: Genes exist in a population in a variety of forms (alleles), as a consequence of multiple mutation events that have arisen over the course of time. In this work we consider a locus that is subject to either multiplicative or additive selection, and has n alleles, where n can take the values 2, 3, 4, . We focus on determining the probability of fixation of each of the n alleles.

Clinical decision-making and dispensing performance in pharmacy students and its relationship to executive function and implicit memory.

Background: When providing pharmaceutical care, the pharmacist relies upon a clinical decision-making process that involves information gathering, clinical reasoning, and clinical judgment. Typically, pharmacists have to identify, retain and recall numerous pieces of key information arranged spatially in medical records and prescriptions or verbally from colleagues when making decisions. Executive function, including spatial working memory and verbal reasoning, along with other cognitive domains, will likely contribute to the elements that comprise this process.

Co-Occurrence of Domestic Dogs and Gastropod Molluscs in Public Dog-Walking Spaces and Implications for Infection with : A Preliminary Study.

is a helminth parasite of domestic dogs that is increasing in range and prevalence. Its lifecycle requires terrestrial gastropod mollusc ("gastropod") intermediate hosts, but research is lacking regarding contact risk in situ. We studied co-occurrence between dogs and gastropods in dog-walking spaces in an hotspot in southern England, United Kingdom, with the aim of quantifying environmental and spatio-temporal overlap.

Decreased 14-3-3 expression correlates with age-related regional reductions in CNS dopamine and motor function in the pond snail, Lymnaea.

Ageing is associated in many organisms with a reduction in motor movements. We have previously shown that the rate of feeding movements of the pond snail, Lymnaea, decreased with age but the underlying cause is not fully understood. Here, we show that dopamine in the cerebro-buccal complex is an important signalling molecule regulating feeding frequency in Lymnaea and that ageing is associated with a decrease in CNS dopamine.

Lethal mutations with fluctuating heterozygous effect: the lethal force of effective dominance.

The theory of population genetics leads to the expectation that in very large populations the frequencies of recessive lethal mutations are close to the square root of the mutation rate, corresponding to mutation-selection balance. There are numerous examples where the frequencies of such alleles are orders of magnitude larger than this result. In this work we theoretically investigate the role of temporal fluctuations in the heterozygous effect (h) for lethal mutations in very large populations.

Influence of Dominance and Drift on Lethal Mutations in Human Populations.

We consider disease-causing mutations that are lethal when homozygous. Lethality involves the very strongest form of negative selection, with the selection coefficient against the disease-carrying homozygote having its maximum value of unity. We determine results for the behavior of the frequency of a lethal allele in an effectively infinite population.

The Association of a Single-Nucleotide Polymorphism in the Nuclear Factor (Erythroid-Derived 2)-Like 2 Gene With Adverse Drug Reactions, Multimorbidity, and Frailty in Older People.

Susceptibility to adverse drug reactions (ADRs), multimorbidity, and frailty are associated with human aging, yet there is wide variation in the severity and age at which individuals are afflicted. Identifying genetic markers of increased risk of this phenotype would help stratify individuals to specialist interventions. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) regulates a cell's response to stressors, including the expression of enzymes involved in drug metabolism.

Correction: Population type influences the rate of ageing.

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Population type influences the rate of ageing.

Mutation accumulation is one of the major genetic theories of ageing and predicts that the frequencies of deleterious alleles that are neutral to selection until post-reproductive years are influenced by random genetic drift. The effective population size (N) determines the rate of drift and in age-structured populations is a function of generation time, the number of newborn individuals and reproductive value. We hypothesise that over the last 50,000 years, the human population survivorship curve has experienced a shift from one of constant mortality and no senescence (known as a Type-II population) to one of delayed, but strong senescence (known as a Type-I population).

Does the 5-HT rs6295 polymorphism influence the safety and efficacy of citalopram therapy in the oldest old?

Major depressive disorder (MDD) in older people is a relatively common, yet hard to treat problem. In this study, we aimed to establish if a single nucleotide polymorphism in the 5-HT receptor gene (rs6295) determines antidepressant response in patients aged > 80 years (the oldest old) with MDD. Nineteen patients aged at least 80 years with a new diagnosis of MDD were monitored for response to citalopram 20 mg daily over 4 weeks and genotyped for the rs6295 allele.

Development of a High-Throughput Burn Wound Model Using Porcine Skin, and Its Application to Evaluate New Approaches to Control Wound Infection.

Biofilm formation in wounds is considered a major barrier to successful treatment, and has been associated with the transition of wounds to a chronic non-healing state. Here, we present a novel laboratory model of wound biofilm formation using porcine skin and a custom burn wound array device. The model supports high-throughput studies of biofilm formation and is compatible with a range of established methods for monitoring bacterial growth, biofilm formation, and gene expression.

The potential role of the sodium iodide symporter gene polymorphism in the development of differentiated thyroid cancer.

The sodium iodide symporter (NIS) (solute carrier family 5; SLC5A), mediates the active transport of iodine anion (I(-)) into thyroid follicular cells to facilitate thyroid hormone biosynthesis. Considering its fundamental role in thyroid function, our objective in this study is to explore its potential involvement in the pathogenesis of differentiated thyroid cancer (DTC). Following a preliminary sequencing of the gene in a representative sample of the general population, five variants, (1) rs45602038, (2) rs4808708, (3) rs4808709, (4) rs7250346 and (5) rs12327843, were selected for a larger population-based association study consisting of 507 cases and 597 controls, of which only the rs45602038_TT [Odds ratio (95% confidence interval)=1.

Heterozygote deficits in cyst plant-parasitic nematodes: possible causes and consequences.

Deviations of genotypic frequencies from Hardy-Weinberg equilibrium (HWE) expectations could reveal important aspects of the biology of populations. Deviations from HWE due to heterozygote deficits have been recorded for three plant-parasitic nematode species. However, it has never been determined whether the observed deficits were due (i) to the presence of null alleles, (ii) to a high level of consanguinity and/or (iii) to a Wahlund effect.

The characteristic trajectory of a fixing allele: a consequence of fictitious selection that arises from conditioning.

This work is concerned with the historical progression, to fixation, of an allele in a finite population. This progression is characterized by the average frequency trajectory of alleles that achieve fixation before a given time, T. Under a diffusion analysis, the average trajectory, conditional on fixation by time T, is shown to be equivalent to the average trajectory in an unconditioned problem involving additional selection.

The association of hypertension with renin-angiotensin system gene polymorphisms in the Lebanese population.

Aim: The study objective was to examine the association of hypertension in the Lebanese population with three renin-angiotensin system gene polymorphisms (RAS): angiotensin-converting enzyme (ACE), angiotensinogen (AGT) and angiotensin-receptor type 1 (AT1R).

Methods: A total of 270 subjects (124 hypertensive vs 146 normotensive) were genotyped for ACE insertion (I)/deletion (D), AGT (M235T), and AT(1)R (A1166C) gene polymorphisms by polymerase chain reaction and restriction fragment length polymorphism.

Results: The studied genes showed no deviation from Hardy-Weinberg equilibrium.

Strain differences and the role of AT(1) receptor expression in anxiety.

This study investigated strain specific differences to the anxiolytic response to losartan focusing on genetic variation that may influence such responses. This included: AT(1) receptor sequence variation, angiotensin II receptor associated protein (ATRAP) and receptor expression between strains. Sequencing of exon 3 of AT(1a)R revealed no differences between BKW mice (n=6) and C57 and DBA(2) strains (n=3).

Strain differences in the effects of angiotensin IV on mouse cognition.

Angiotensin IV has been shown to improve learning and memory in rodents. Strain dependent variation in murine behaviour, aminopeptidase activity and inhibitory effect of Angiotensin IV, structural variation in insulin regulated aminopeptidase (IRAP) and aminopeptidase N (ApN) and expression of the encoding genes were explored. Strain differences in the behavioural response to Angiotensin IV were observed, where CD mice were refractory.

The geographic distribution of the ACE II genotype: a novel finding.

Angiotensin converting enzyme (ACE) gene polymorphism insertion (I) or deletion (D) has been widely studied in different populations, and linked to various functional effects and associated with common diseases. The purpose of the present study was to investigate the relationship between the ACE I/D frequency in different populations and geographic location; ACE I/D allele frequency in the Lebanese population and ACE II genotype contribution to the geographic trend were also identified. Five hundred and seventy healthy volunteers were recruited from the Lebanese population.

Heterozygosity, inbreeding and neonatal traits in Soay sheep on St Kilda.

We investigated whether birth weight and neonatal survival, a period within which 24% of all mortalities occur, were correlated with levels of inbreeding in St Kilda Soay sheep, using pedigree inbreeding coefficients and four marker-based estimators of inbreeding. None of the inbreeding estimators, either of the offspring, or of their mothers, explained significant variation in a lamb's birth weight or probability of surviving the neonatal period, suggesting low inbreeding depression for these traits. We evaluated the correlation between the marker-based measures of inbreeding and inbreeding coefficients obtained from the Soay pedigree, where paternal links were inferred using the same panel of microsatellite markers.

Selection on mothers and offspring: whose phenotype is it and does it matter?

Reproductive and early life-history traits can be considered aspects of either offspring or maternal phenotype, and their evolution will therefore depend on selection operating through offspring and maternal components of fitness. Furthermore, selection at these levels may be antagonistic, with optimal offspring and maternal fitness occurring at different phenotypic values. We examined selection regimes on the correlated traits of birth weight, birth date, and litter size in Soay sheep (Ovis aries) using data from a long-term study of a free-living population on the archipelago of St.

Maternal genetic effects set the potential for evolution in a free-living vertebrate population.

Heritable maternal effects have important consequences for the evolutionary dynamics of phenotypic traits under selection, but have only rarely been tested for or quantified in evolutionary studies. Here we estimate maternal effects on early-life traits in a feral population of Soay sheep (Ovis aries) from St Kilda, Scotland. We then partition the maternal effects into genetic and environmental components to obtain the first direct estimates of maternal genetic effects in a free-living population, and furthermore test for covariance between direct and maternal genetic effects.

An analysis of consanguinity and social structure within the UK Asian population using microsatellite data.

We analysed microsatellite genotypes sampled from the Pakistani and Indian communities in Nottingham, UK, to investigate the genetic consequences of substructuring mediated by traditional marriage customs. The application of a recently developed likelihood approach identified significant levels of population substructure within the Pakistani community as a whole, as well as within the finer divisions of castes and biradheri. In addition, high levels of cryptic or unacknowledged consanguinity were detected within subgroups of this community, including biradheri.

Population genetic structure of the lettuce root aphid, Pemphigus bursarius (L.), in relation to geographic distance, gene flow and host plant usage.

Microsatellite markers were used to examine the population structure of Pemphigus bursarius, a cyclically parthenogenetic aphid. Substantial allele frequency differences were observed between populations on the primary host plant (collected shortly after sexual reproduction) separated by distances as low as 14 km. This suggested that migratory movements occur over relatively short distances in this species.