Demographic changes and marker properties affect detection of human population differentiation

<p>Abstract</p> <p>Background</p> <p>Differentiating genetically between populations is valuable for admixture and population stratification detection and in understanding population history. This is easy to achieve for major continental populations, but not for closely related populations. It has been claimed that a large marker panel is necessary to reliably distinguish populations within a continent. We investigated whether empirical genetic differentiation could be accomplished efficiently among three Asian populations (Hmong, Thai, and Chinese) using a small set of highly variable markers (15 tetranucleotide and 17 dinucleotide repeats).</p> <p>Results</p> <p>Hmong could be differentiated from Thai and Chinese based on multi-locus genotypes, but Thai and Chinese were indistinguishable from each other. We found significant evidence for a recent population bottleneck followed by expansion in the Hmong that was not present in the Thai or Chinese. Tetranucleotide repeats were less useful than dinucleotide repeat markers in distinguishing between major continental populations (Asian, European, and African) while both successfully distinguished Hmong from Thai and Chinese.</p> <p>Conclusion</p> <p>Demographic history contributes significantly to robust detection of intracontinental population structure. Populations having experienced a rapid size reduction may be reliably distinguished as a result of a genetic drift -driven redistribution of population allele frequencies. Tetranucleotide markers, which differ from dinucleotide markers in mutation mechanism and rate, are similar in information content to dinucleotide markers in this situation. These factors should be considered when identifying populations suitable for gene mapping studies and when interpreting interpopulation relationships based on microsatellite markers.</p

Dynamic Gene Expression in the Human Cerebral Cortex Distinguishes Children from Adults

In comparison with other primate species, humans have an extended juvenile period during which the brain is more plastic. In the current study we sought to examine gene expression in the cerebral cortex during development in the context of this adaptive plasticity. We introduce an approach designed to discriminate genes with variable as opposed to uniform patterns of gene expression and found that greater inter-individual variance is observed among children than among adults. For the 337 transcripts that show this pattern, we found a significant overrepresentation of genes annotated to the immune system process (pFDR≅0). Moreover, genes known to be important in neuronal function, such as brain-derived neurotrophic factor (BDNF), are included among the genes more variably expressed in childhood. We propose that the developmental period of heightened childhood neuronal plasticity is characterized by more dynamic patterns of gene expression in the cerebral cortex compared to adulthood when the brain is less plastic. That an overabundance of these genes are annotated to the immune system suggests that the functions of these genes can be thought of not only in the context of antigen processing and presentation, but also in the context of nervous system development

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Memories of vacant lots: how and why residents used informal urban green space as children and teenagers in Brisbane, Australia, and Sapporo, Japan

Contact with nature is vital for the development of children and teenagers. In the past, informal urban green spaces (IGS) such as vacant lots appear to have been used for such purposes. We need to better understand how previous generations used IGS to make sure young people today can also enjoy its social, mental, emotional and physical health benefits. This study quantitatively compared adult residents' memories of IGS use in their childhood and teenage years in two geographically and culturally distinct cities: Brisbane, Australia, and Sapporo, Japan. The results showed most respondents (>70%) remembered using IGS in the past, and preferred it over other green space because it was easily accessible. Most (>70%) recalled experiencing no problems (e.g. danger of injury) when using IGS, a contrast to recently increasing parental concern for children's safety. Such factors may limit present IGS use and prevent it from fulfilling the important role it played for previous generations' recreation

New SNP data for 64 Yemeni

Contains the complete unfiltered new genotype data from 64 Yemeni samples in a binary PED (BED) file format (compatible with PLINK). These samples were collected by Connie Mulligan, Ali Al-Meeri, and Ryan Raaum in the spring of 2007 in Yemen with grant support from NSF BCS-0518530 to Connie Mulligan. These samples were genotyped on the Illumina Human CNV370-Quad V3.0 Beadchip. The chromosome and map location information in the bed map file are as provided in the Illumina documentation for this chip. As of April 22, 2014, Illumina has information on this chip at: http://support.illumina.com/downloads/humancnv370-quad_v30_product_files.ilm

Tests of gene flow and population structure in the non-African ancestry of HOA populations.

<p>Using the non-African origin partition of the HOA data identified in a chromosome painting analysis, we evaluated the evidence for gene flow with MENA populations and for population structure within and between the HOA and MENA populations. (A) The only clear and statistically significant pattern of decreasing gene identity with geographic distance was between HOA populations and the Yemen and Saudi Arabia populations on the Arabian peninsula as evaluated by a Mantel test. This relationship only held for “as the crow flies” geographic distances; the relationship disappears using a waypoint through Egypt (<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004393#pgen.1004393.s003" target="_blank">Figure S3</a>). (B) Shared gene identity between the non-African ancestry partition of HOA populations and MENA populations presented in increasing order. (C) Structured population tree model within the non-African ancestry partition of HOA populations with the <i>F_ST</i> estimate from this tree model, the goodness-of-fit statistic Λ, and the likelihood ratio test statistic K for the improvement in model fit from the unstructured tree. (D) Structured population tree model within the non-African ancestry partition of MENA populations. (E) Structured population tree models for the non-African ancestry partitions of both HOA and MENA populations. Both are significantly better fits to the data than the unstructured tree and the regional structure (HOA vs MENA) is a slightly better fit to the data as measured by the goodness-of-fit Λ statistic.</p

Estimated mean proportion of ancestry (greater than 5%) in Horn of Africa populations.¹

1<p>None of the Horn of Africa populations have 5% or greater ancestry from Khoesan, Pygmy, Maghrebi, European, South Asian, or East Asian ancestral populations, so these ancestries are not shown in the table.</p

Estimates of admixture dates in Horn of Africa populations (ka).¹

1<p>Using 30 years per generation.</p>2<p>Single admixture fit.</p>3<p>Two admixtures fits that are significantly better than the single admixture fit.</p>†<p>ALDER test for admixture not significant.</p><p>* ALDER reports inconsistent decay rates.</p