4000 years of phenotypic change in an island bird: heterogeneity of selection over three microevolutionary timescales.

Pronounced phenotypic shifts in island populations are typically attributed to natural selection, but reconstructing heterogeneity in long-term selective regimes remains a challenge. We examined a scenario of divergence proposed for species colonizing a new environment, involving directional selection with a rapid shift to a new optimum and subsequent stabilization. We provide some of the first empirical evidence for this model of evolution using morphological data from three timescales in an island bird, Zosterops lateralis chlorocephalus. In less than four millennia since separation from its mainland counterpart, a substantial increase in body size has occurred and was probably achieved in fewer than 500 generations after colonization. Over four recent decades, morphological traits have fluctuated in size but showed no significant directional trends, suggesting maintenance of a relatively stable phenotype. Finally, estimates of contemporary selection gradients indicated generally weak directional selection. These results provide a rare description of heterogeneity in long-term natural regimes, and caution that observations of current selection may be of limited value in inferring mechanisms of past adaptation due to a lack of constancy even over short time-frames.

The association between pterygium and conjunctival ultraviolet autofluorescence : The Norfolk Island Eye Study

Purpose: To investigate the association between conjunctival ultraviolet autofluorescence (UVAF), a biomarker of ocular ultraviolet radiation (UVR) exposure, and prevalent pterygium. Methods: We conducted a cross-sectional study on Norfolk Island, South Pacific. All permanent residents aged ‡15 were invited to participate. Participants completed a sun exposure questionnaire and underwent autorefraction and slit lamp biomicroscope examination. Area of conjunctival UVAF (sum of temporal ⁄ nasal area in right and left eyes) was determined using computerized methods. Multivariate logistic and linear regression models were used to estimate the associations with pterygia and UVAF, respectively. Results: Of 641 participants, 70 people (10.9%) had pterygium in one or both eyes, and prevalence was higher in males (15.0% versus 7.7%, p = 0.003). Significant independent associations with pterygium in any eye were UVAF (per 10 mm2) [odds ratio (OR) 1.16, 95% confidence interval (CI) 1.16–1.28, p = 0.002], tanning skin phenotype (OR 2.17,1.20–3.92, p = 0.010) and spending more than three-quarters of the day outside (OR 2.22, 1.20–4.09, p = 0.011). Increasing quartile of UVAF was associated with increased risk of pterygium following adjustment of age, sex and time outdoors (pTrend = 0.002). Independent associations with increasing UVAF (per 10 mm2) were decreasing age, time outdoors, skin type and male gender (all p < 0.001). UVAF area correlated well with the duration of outdoor activity (pTrend < 0.001). Conclusion: Pterygium occurs in approximately one-tenth of Norfolk Islanders. Increasing conjunctival UVAF is associated with prevalent pterygia, confirming earlier epidemiological, laboratory and ray-tracing studies that pterygia are associated with UVR. Protection from the sun should be encouraged to reduce the prevalence of pterygium in the community.

Heritability and genome-wide linkage analysis of migraine in the genetic isolate of Norfolk Island

Migraine is a common neurovascular disorder with a complex envirogenomic aetiology. In an effort to identify migraine susceptibility genes, we conducted a study of the isolated population of Norfolk Island, Australia. A large portion of the permanent inhabitants of Norfolk Island are descended from 18th Century English sailors involved in the infamous mutiny on the Bounty and their Polynesian consorts. In total, 600 subjects were recruited including a large pedigree of 377 individuals with lineage to the founders. All individuals were phenotyped for migraine using International Classification of Headache Disorders-II criterion. All subjects were genotyped for a genome-wide panel of microsatellite markers. Genotype and phenotype data for the pedigree were analysed using heritability and linkage methods implemented in the programme SOLAR. Follow-up association analysis was performed using the CLUMP programme. A total of 154 migraine cases (25%) were identified indicating the Norfolk Island population is high-risk for migraine. Heritability estimation of the 377-member pedigree indicated a significant genetic component for migraine (h2 = 0.53, P = 0.016). Linkage analysis showed peaks on chromosome 13q33.1 (P = 0.003) and chromosome 9q22.32 (P = 0.008). Association analysis of the key microsatellites in the remaining 223 unrelated Norfolk Island individuals showed evidence of association, which strengthen support for the linkage findings (P ≤ 0.05). In conclusion, a genome-wide linkage analysis and follow-up association analysis of migraine in the genetic isolate of Norfolk Island provided evidence for migraine susceptibility loci on chromosomes 9q22.22 and 13q33.1.

Linkage mapping of CVD risk traits in the isolated Norfolk Island population

To understand the underlying genetic architecture of cardiovascular disease (CVD) risk traits, we undertook a genome-wide linkage scan to identify CVD quantitative trait loci (QTLs) in 377 individuals from the Norfolk Island population. The central aim of this research focused on the utilization of a genetically and geographically isolated population of individuals from Norfolk Island for the purposes of variance component linkage analysis to identify QTLs involved in CVD risk traits. Substantial evidence supports the involvement of traits such as systolic and diastolic blood pressures, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, body mass index and triglycerides as important risk factors for CVD pathogenesis. In addition to the environmental inXuences of poor diet, reduced physical activity, increasing age, cigarette smoking and alcohol consumption, many studies have illustrated a strong involvement of genetic components in the CVD phenotype through family and twin studies. We undertook a genome scan using 400 markers spaced approximately 10 cM in 600 individuals from Norfolk Island. Genotype data was analyzed using the variance components methods of SOLAR. Our results gave a peak LOD score of 2.01 localizing to chromosome 1p36 for systolic blood pressure and replicated previously implicated loci for other CVD relevant QTLs.

Identification of genetic variants contributing to the migraine phenotype in different Australian populations

This project aimed to identify novel genetic risk variants associated with migraine in the Norfolk Island population. Statistical analysis and bioinformatics approaches such as polygenic modeling and gene clustering methods were carried out to explore genotypic and expression data from high-throughput techniques. This project had a particular focus on hormonal genes and other genetic variants and identified a modest effect size on the migraine phenotype.

A Phenomic Scan of the Norfolk Island Genetic Isolate Identifies a Major Pleiotropic Effect Locus Associated with Metabolic and Renal Disorder Markers

Multiphenotype genome-wide association studies (GWAS) may reveal pleiotropic genes, which would remain undetected using single phenotype analyses. Analysis of large pedigrees offers the added advantage of more accurately assessing trait heritability, which can help prioritise genetically influenced phenotypes for GWAS analysis. In this study we performed a principal component analysis (PCA), heritability (h2) estimation and pedigree-based GWAS of 37 cardiovascular disease -related phenotypes in 330 related individuals forming a large pedigree from the Norfolk Island genetic isolate. PCA revealed 13 components explaining >75% of the total variance. Nine components yielded statistically significant h2 values ranging from 0.22 to 0.54 (P<0.05). The most heritable component was loaded with 7 phenotypic measures reflecting metabolic and renal dysfunction. A GWAS of this composite phenotype revealed statistically significant associations for 3 adjacent SNPs on chromosome 1p22.2 (P<1x10-8). These SNPs form a 42kb haplotype block and explain 11% of the genetic variance for this renal function phenotype. Replication analysis of the tagging SNP (rs1396315) in an independent US cohort supports the association (P = 0.000011). Blood transcript analysis showed 35 genes were associated with rs1396315 (P<0.05). Gene set enrichment analysis of these genes revealed the most enriched pathway was purine metabolism (P = 0.0015). Overall, our findings provide convincing evidence for a major pleiotropic effect locus on chromosome 1p22.2 influencing risk of renal dysfunction via purine metabolism pathways in the Norfolk Island population. Further studies are now warranted to interrogate the functional relevance of this locus in terms of renal pathology and cardiovascular disease risk.

Mutation frequency of non-ESBL phenotype SENTRY (Asia-Pacific) isolates of Klebsiella pneumoniae conversion to an ESBL positive phenotype

Extended spectrum β-lactamases or ESBLs, which are derived from non-ESBL precursors by point mutation of β-lactamase genes (bla), are spreading rapidly all over the world and have caused considerable problems in the treatment of infections caused by bacteria which harbour them. The mechanism of this resistance is not fully understood and a better understanding of these mechanisms might significantly impact on choosing proper diagnostic and treatment strategies. Previous work on SHV β-lactamase gene, blaSHV, has shown that only Klebsiella pneumoniae strains which contain plasmid-borne blaSHV are able to mutate to phenotypically ESBL-positive strains and there was also evidence of an increase in blaSHV copy number. Therefore, it was hypothesised that although specific point mutation is essential for acquisition of ESBL activity, it is not yet enough, and blaSHV copy number amplification is also essential for an ESBL-positive phenotype, with homologous recombination being the likely mechanism of blaSHV copy number expansion. In this study, we investigated the mutation rate of non-ESBL expressing K. pneumoniae isolates to an ESBL-positive status by using the MSS-maximum likelihood method. Our data showed that blaSHV mutation rate of a non-ESBL expressing isolate is lower than the mutation rate of the other single base changes on the chromosome, even with a plasmid-borne blaSHV gene. On the other hand, mutation rate from a low MIC ESBL-positive (≤ 8 µg/mL for cefotaxime) to high MIC ESBL-positive (≥16 µg/mL for cefotaxime) is very high. This is because only gene copy number increase is needed which is probably mediated by homologous recombination that typically takes place at a much higher frequencies than point mutations. Using a subinhibitory concentration of novobiocin, as a homologous recombination inhibitor, revealed that this is the case.

The Queensland study of melanoma : Environmental and genetic associations (Q-MEGA); Study design, baseline characteristics, and repeatability of phenotype and sun exposure measures

Cutaneous malignant melanoma (CMM) is a major health issue in Queensland, Australia, which has the world’s highest incidence. Recent molecular and epidemiologic studies suggest that CMM arises through multiple etiological pathways involving gene-environment interactions. Understanding the potential mechanisms leading to CMM requires larger studies than those previously conducted. This article describes the design and baseline characteristics of Q-MEGA, the Queensland Study of Melanoma: Environmental and Genetic Associations, which followed up 4 population-based samples of CMM patients in Queensland, including children, adolescents, men aged over 50, and a large sample of adult cases and their families, including twins. Q-MEGA aims to investigate the roles of genetic and environmental factors, and their interaction, in the etiology of melanoma. Three thousand, four hundred and seventy-one participants took part in the follow-up study and were administered a computer-assisted telephone interview in 2002-2005. Updated data on environmental and phenotypic risk factors, and 2777 blood samples were collected from interviewed participants as well as a subset of relatives. This study provides a large and well-described population-based sample of CMM cases with follow-up data. Characteristics of the cases and repeatability of sun exposure and phenotype measures between the baseline and the follow-up surveys, from 6 to 17 years later, are also described.

Torres Strait Island parents' involvement in their children's mathematics learning : a discussion paper

This paper is a beginning point for discussing what the literature states about parents’ involvement in their children’s mathematics education. Where possible it will focus on Torres Strait Islander Peoples. Little is known about how Torres Strait Islander parents approach their children’s learning of mathematics and how important early mathematics is to mothers. What is known is that is they are keen for their children to receive an education that provides them with opportunities for their present and future lives. However, gaining access to education is challenging given that the language of instruction in schools is written to English conventions, decontextualised and disconnected from the students’ culture, community and home language. This paper discusses some of the issues raised in the literature about what parents are confronted with when making decisions about their children’s education.

Info-gap theory and robust design of surveillance for invasive species : the case study of Barrow Island

Surveillance for invasive non-indigenous species (NIS) is an integral part of a quarantine system. Estimating the efficiency of a surveillance strategy relies on many uncertain parameters estimated by experts, such as the efficiency of its components in face of the specific NIS, the ability of the NIS to inhabit different environments, and so on. Due to the importance of detecting an invasive NIS within a critical period of time, it is crucial that these uncertainties be accounted for in the design of the surveillance system. We formulate a detection model that takes into account, in addition to structured sampling for incursive NIS, incidental detection by untrained workers. We use info-gap theory for satisficing (not minimizing) the probability of detection, while at the same time maximizing the robustness to uncertainty. We demonstrate the trade-off between robustness to uncertainty, and an increase in the required probability of detection. An empirical example based on the detection of Pheidole megacephala on Barrow Island demonstrates the use of info-gap analysis to select a surveillance strategy.