Dataset Information

Validation of a cost-efficient multi-purpose SNP panel for disease based research.

ABSTRACT: Here we present convergent methodologies using theoretical calculations, empirical assessment on in-house and publicly available datasets as well as in silico simulations, that validate a panel of SNPs for a variety of necessary tasks in human genetics disease research before resources are committed to larger-scale genotyping studies on those samples. While large-scale well-funded human genetic studies routinely have up to a million SNP genotypes, samples in a human genetics laboratory that are not yet part of such studies may be productively utilized in pilot projects or as part of targeted follow-up work though such smaller scale applications require at least some genome-wide genotype data for quality control purposes such as DNA "barcoding" to detect swaps or contamination issues, determining familial relationships between samples and correcting biases due to population effects such as population stratification in pilot studies.Empirical performance in classification of relative types for any two given DNA samples (e.g., full siblings, parental, etc) indicated that for outbred populations the panel performs sufficiently to classify relationship in extended families and therefore also for smaller structures such as trios and for twin zygosity testing. Additionally, familial relationships do not significantly diminish the (mean match) probability of sharing SNP genotypes in pedigrees, further indicating the uniqueness of the "barcode." Simulation using these SNPs for an African American case-control disease association study demonstrated that population stratification, even in complex admixed samples, can be adequately corrected under a range of disease models using the SNP panel.The panel has been validated for use in a variety of human disease genetics research tasks including sample barcoding, relationship verification, population substructure detection and statistical correction. Given the ease of genotyping our specific assay contained herein, this panel represents a useful and economical panel for human geneticists.

SUBMITTER: Hou L

PROVIDER: S-EPMC3096622 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Validation of a cost-efficient multi-purpose SNP panel for disease based research.

Hou Liping L Phillips Christopher C Azaro Marco M Brzustowicz Linda M LM Bartlett Christopher W CW

PloS one 20110517 5

<h4>Background</h4>Here we present convergent methodologies using theoretical calculations, empirical assessment on in-house and publicly available datasets as well as in silico simulations, that validate a panel of SNPs for a variety of necessary tasks in human genetics disease research before resources are committed to larger-scale genotyping studies on those samples. While large-scale well-funded human genetic studies routinely have up to a million SNP genotypes, samples in a human genetics l ...[more]

PMID: 21611176

Similar Datasets

Project description:INTRODUCTION:A number of antiretroviral HIV prevention products are efficacious in preventing HIV infection. However, the sexual and reproductive health needs of many women extend beyond HIV prevention, and research is ongoing to develop multi-purpose prevention technologies (MPTs) that offer dual HIV and pregnancy protection. We do not yet know if these products will be an efficient use of constrained health resources. In this paper, we estimate the cost-effectiveness of combinations of candidate multi-purpose prevention technologies (MPTs), in South Africa among general population women and female sex workers (FSWs). METHODS:We combined a cost model with a static model of product impact based on incidence data in South Africa to estimate the cost-effectiveness of five candidate co-formulated or co-provided MPTs: oral PrEP, intravaginal ring, injectable ARV, microbicide gel and SILCS diaphragm used in concert with gel. We accounted for the preferences of end-users by predicting uptake using a discrete choice experiment (DCE). Product availability and protection were systematically varied in five potential rollout scenarios. The impact model estimated the number of infections averted through decreased incidence due to product use over one year. The comparator for each scenario was current levels of male condom use, while a health system perspective was used to estimate discounted lifetime treatment costs averted per HIV infection. Product benefit was estimated in disability-adjusted life years (DALYs) averted. Benefits from contraception were incorporated through adjusting the uptake of these products based on the DCE and through estimating the costs averted from avoiding unwanted pregnancies. We explore the additional impact of STI protection through increased uptake in a sensitivity analysis. RESULTS:At central incidence rates, all single- and multi-purpose scenarios modelled were cost-effective among FSWs and women aged 16-24, at a governmental willingness-to-pay threshold of $1175/DALY averted (range: $214-$810/DALY averted among non-dominant scenarios), however, none were cost-effective among women aged 25-49 (minimum $1706/DALY averted). The cost-effectiveness of products improved with additional protection from pregnancy. Estimates were sensitive to variation in incidence assumptions, but robust to other parameters. CONCLUSIONS:To the best of our knowledge, this is the first study to estimate the cost-effectiveness of a range of potential MPTs; suggesting that MPTs will be cost-effective among higher incidence FSWs or young women, but not among lower incidence older women. More work is needed to make attractive MPTs available to potential users who could use them effectively.

Project description:The objective of this study was to develop and validate a customized cost-effective single nucleotide polymorphism (SNP) panel for genetic improvement of feed efficiency in beef cattle. The SNPs identified in previous association studies and through extensive analysis of candidate genomic regions and genes, were screened for their functional impact and allele frequency in Angus and Hereford breeds used as validation candidates for the panel. Association analyses were performed on genotypes of 159 SNPs from new samples of Angus (n = 160), Hereford (n = 329), and Angus-Hereford crossbred (n = 382) cattle using allele substitution and genotypic models in ASReml. Genomic heritabilities were estimated for feed efficiency traits using the full set of SNPs, SNPs associated with at least one of the traits (at P ? 0.05 and P < 0.10), as well as the Illumina bovine 50K representing a widely used commercial genotyping panel. A total of 63 SNPs within 43 genes showed association (P ? 0.05) with at least one trait. The minor alleles of SNPs located in the GHR and CAST genes were associated with decreasing effects on residual feed intake (RFI) and/or RFI adjusted for backfat (RFIf), whereas minor alleles of SNPs within MKI67 gene were associated with increasing effects on RFI and RFIf. Additionally, the minor allele of rs137400016 SNP within CNTFR was associated with increasing average daily gain (ADG). The SNPs genotypes within UMPS, SMARCAL, CCSER1, and LMCD1 genes showed significant over-dominance effects whereas other SNPs located in SMARCAL1, ANXA2, CACNA1G, and PHYHIPL genes showed additive effects on RFI and RFIf. Gene enrichment analysis indicated that gland development, as well as ion and cation transport are important physiological mechanisms contributing to variation in feed efficiency traits. The study revealed the effect of the Jak-STAT signaling pathway on feed efficiency through the CNTFR, OSMR, and GHR genes. Genomic heritability using the 63 significant (P ? 0.05) SNPs was 0.09, 0.09, 0.13, 0.05, 0.05, and 0.07 for ADG, dry matter intake, midpoint metabolic weight, RFI, RFIf, and backfat, respectively. These SNPs contributed to genetic variation in the studied traits and thus can potentially be used or tested to generate cost-effective molecular breeding values for feed efficiency in beef cattle.

Project description:BackgroundMeaning in life is multidimensional. It encompasses different qualities of meaning, such as meaningfulness, crisis of meaning, or existential indifference, as well as the sources from which people draw meaning, or purpose. For both research and practice, it is of high value to know not only the extent of meaningfulness, or its absence, but also its sources. How do these relate to meaningfulness and mental health? Are they accessible to people of different sociodemographic and economic backgrounds alike? For therapeutic and counseling practice, knowledge of experiences and sources of meaning is needed to support a clearer self-understanding in patients or clients and to encourage them to make authentic life choices. The Meaning and Purpose Scales (MAPS) presented here enable researchers and practitioners to gain insights into these dimensions of meaning in life, and, with only 23 items, to do so in a short time.MethodsUsing five independent and two follow-up samples with a total N of 7,500, this paper examined the MAPS' internal consistency, test-retest reliability, and convergent, divergent, criterion, factorial, and predictive validity.ResultsPrincipal axis factoring identified two meaning scales, Meaningfulness and Crisis of Meaning, and five purpose scales, Sustainability, Faith, Security, Community, and Personal Growth. The scales proved consistent, stable over four weeks and two months, and valid in multiple respects. In a representative German population sample, Personal Growth, Sustainability, and Community exhibited large, Faith and Security medium positive relationships with Meaningfulness, whereas Crisis of Meaning showed small to moderate negative correlations. Meaningfulness was positively, and Crisis of Meaning negatively predicted by age, partnership, parenthood, and religious affiliation. Financial hardship correlated positively with Crisis of Meaning and negatively with Meaningfulness, Community, and Personal Growth. Meaningfulness and Crisis of Meaning explained 21%, the sources of purpose 6% of additional variance in general mental distress (PHQ-4), beyond sociodemographics. Except for Faith (unrelated), all sources exhibited moderate negative correlations with the PHQ-4.ConclusionAs this series of studies demonstrates, the MAPS provide a highly economic and valid assessment of two qualities of meaning, Meaningfulness and Crisis of Meaning, and five sources of purpose: Sustainability, Faith, Security, Community, and Personal Growth.

Dataset Information

Validation of a cost-efficient multi-purpose SNP panel for disease based research.

Publications

Validation of a cost-efficient multi-purpose SNP panel for disease based research.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets