Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Genomic testing costs”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3Linked to original sources
PubMed2004

Accurate multiplex gene synthesis from programmable DNA microchips.

Testing the many hypotheses from genomics and systems biology experiments demands accurate and cost-effective gene and genome synthesis. Here we describe a microchip-based technology for multiplex gene synthesis. Pools of thousands of 'construction' oligonucleotides and tagged complementary 'selection' oligonucleotides are synthesized on photo-programmable microfluidic chips, released, amplified and selected by hybridization to reduce synthesis errors ninefold. A one-step polymerase assembly multiplexing reaction assembles these into multiple genes. This technology enabled us to synthesize all 21 genes that encode the proteins of the Escherichia coli 30S ribosomal subunit, and to optimize their translation efficiency in vitro through alteration of codon bias. This is a significant step towards the synthesis of ribosomes in vitro and should have utility for synthetic biology in general.

Escherichia coli↗
PubMed1997

[Anti-hepatitis C prevalence and incidence in 2.8 million blood donors in Lower Saxony--residual transfusion-associated HCV risk].

561 out of 2,777,021 blood donations from 582,655 donors tested confirmed positive for anti-HCV (RIBA II or Matrix Dot), 549 of them at their first donation, in their first HCV test ever, or in the first HCV test with a new, more sensitive test generation. Thus, our anti-HCV prevalence is 0.037% or 1 in 2,679 donations; among first-time donations it is five times higher than among repeat donations. Twelve repeat donors seroconverted, yielding an anti-HCV incidence of 0.0008% or 1 in 122,570 repeat donations and a seroconversion rate of 2.32 per 10(5) repeat donor person-years. The residual risk associated with transfusion of blood for repeat donors amounts to 5.2 per 10(6) repeat donations. We estimate a risk reduction from introduction of direct virus genome testing after PCR to be at 3.7 per 10(6) repeat donations. Look-backs among recipients of the last seronegative blood products from 12 donors with subsequent seroconversion revealed no recipient infection. Thus, today the residual risk for HCV transmission through transfusion of blood components obtained from Lower Saxony blood donors is quite low. The added safety from direct virus genome testing after PCR is considered extremely low, which casts doubt on the cost-effectiveness of such a measure.

Blood Donors↗
PubMed2000

HIV-1 drug resistance genotyping. A review of clinical and economic issues.

The development of mutations associated with resistance to antiretroviral therapy (ART) has been shown to be a major cause of treatment failure in patients infected with HIV-1. These resistance mutations can be assessed by a genotyping test that probes for specific mutations within the HIV genome or sequences specific genes, at a cost $US500/test (2000 prices). The stated goal of HIV-1 genotyping is to target HIV therapy effectively. This, as shown in the preliminary research, should result in better clinical outcomes and a lower incidence of virological failure and may be associated with lower costs of treatment. Failure of ART may result in an increase in costs of at least $US250 per patient per month, as assessed in 1 study, with costs rising further as patients experience multiple virological failures. Therefore, there is an economic as well as a therapeutic premium on the prevention of ART failure. The actual economic cost of genotyping has been preliminarily explored in the context of the antiretroVIRal ADAPTation (VIRADAPT) trial, which found no significant difference in the 1-year treatment cost of patients with and without genotyping. There is some evidence of cost neutrality or savings with genotypic testing but it needs to be further explored within the context of carefully framed prospective trials.

Anti-HIV Agents↗
PubMed2000

A single, sequential, genome-wide test to identify simultaneously all promising areas in a linkage scan.

Inflation of type I error occurs when conducting a large number of statistical tests in genome-wide linkage scans. Stringent alpha-levels protect against the high numbers of expected false positives but at the cost of more false negatives. A more balanced tradeoff is provided by the theory of sequential analysis, which can be used in a genome scan even when the data are collected using a fixed-sample design. Sequential tests allow complete, simultaneous control of both the type I and II errors of each individual test while using the smallest possible sample size for analysis. For fixed samples, the excess N "saved" can be used in a confirmatory, replication phase of the original findings. Using the theory of sequential multiple decision procedures [Bechhoffer et al., 1968], we can replace the series of individual marker tests with a new single, simultaneous genome-wide test that has multiple possible outcomes and partitions all markers into two subsets: the "signal" versus the "noise," with an a priori specifiable genome-wide error rate. These tests are demonstrated for the Haseman-Elston approach, are applied to real data, and are contrasted with traditional fixed-sampling tests in Monte Carlo simulations of repeated genome-wide scans. The method allows efficient identification of the true signals in a genome scan, uses the smallest possible sample sizes, saves the excess to confirm those findings, controls both types of error, and provides one elegant solution to the debate over the best way to balance between false positives and negatives in genome scans.

Dopamine beta-Hydroxylase↗
PubMed2005

Detection of known haemophilia B mutations and carrier testing by microarray.

The molecular basis of haemophilia B is heterogeneous and many mutations of the Factor IX (FIX) gene have been characterised. Using the allele-specific arrayed primer extension (AS-APEX) technology, we have designed a FIX array to simultaneously analyse 69 mutations found in British, Thai and Chinese patients. This technology overcomes the problem of multiple reverse dot-blot analysis and has a 100% accuracy in the detection of both affected subjects and carriers in families with known mutations. In seven unknown mutations from Thailand, the array could detect the specific mutation in five and in the remainders the normal primer at specific spots failed to extend due to a mutation a few nucleotides upstream, thus allowing their identification. Hence this FIX array can detect 53% of the 2891 mutation entries in the FIX database. Each of the microarray slide can be used for three different test samples and would be useful for carrier testing for common mutations and prenatal diagnosis. It is simpler and more cost effective than genome sequencing and would be particularly useful in laboratories with limited technical capabilities.

Base Sequence↗
PubMed2006

Global pharmacogenetics: giving the genome to the masses.

With pharmacogenetics comes the promise of individualized therapy selection for many common diseases where multiple treatment options are available. Recent advances including the Human Genome Project, the International HapMap project, advances in throughput and reduction in cost of genetic testing, and the inclusion of genotype-related dosing recommendations into package inserts all point to the integration of pharmacogenetics into clinical practice. However, many countries will not have access to pharmacogenetics resources in the near future. Generation of global genotype profiles will provide a useful, but not perfect resource for incorporating pharmacogenetics into national drug formularies in the form of prioritization or surveillance where individual genotype data would not be attainable. The PharmacoGenetics for Every Nation Initiative is a first step to making pharmacogenetics applicable on a global level.

Drug Therapy↗
PubMed2001

[Host genetic epidemiology by single nucleotide polymorphism(SNP) analysis].

The completion of the whole human genome sequences is now a reality. Emphasis on the analysis of genetic variations on both an individual level and a population level is more important than ever. The identification and characterization of single nucleotide polymorphisms (SNPs) in target genes or candidate genes plays a crucial role in identification of disease genes and in expediting drug discovery/development. Identification of known SNPs can be easily accomplished by searching the ever-expanding public domain databases. However, discovery of new SNPs is best accomplished by sequencing a reasonable subset of the applicable population groups. Particular SNPs of interest will be the ones that affect coding changes and regulatory functions of genes. Once SNPs have been identified, the next step is to examine their frequency in disease models by accurate, cost-effective and high-throughput SNP genotyping methods. This presentation will cover the overview of principal techniques of SNP genotyping which have been developed so far. And also will be discussed the importance of well-defined disease model and error-free high-throughput SNP genotyping in candidate genes and genome-wide SNP screening in the near future.

Alleles↗
PubMed1996

The Human Genome Project and the clinician.

The Florida Supreme Court's decision in Pate v Threlkel is an early warning sing of the massive impact human genome research will have on medical practice. Genetic screening is a scientific tool whose widespread use in clinical medicine will expand due to the combined influences of the federally funded Human Genome Project, biotechnology market forces, and corporate and societal pressures to both use and further develop the technique. Once testing becomes cost-effective, clinicians, by virtue of their position as "knowledgeable professionals" and as the primary source of health information for patients with genetic disorders, will be required to act as gatekeepers to the genetic heritage of their patients. This will seriously impact the legal definitions of reasonable care, a physician's duty to warn, the concept of informed consent, and the confidentiality of medical records.

Biotechnology↗
PubMed2006

Optimal two-stage genotyping designs for genome-wide association scans.

The much-anticipated fixed-array, genome-wide SNP genotyping technologies make large-scale genome-wide association scans now possible for large numbers of subjects. In this paper we reconsider the problem (Satagopan and Elston [2003] Genet Epidemiol 25:149-157) of optimizing a two-stage genotyping design to deal with important new issues that are relevant when studies are expanded from candidate gene size to a genome-wide scale. We investigate how the basic two-stage genotyping approach, in which all markers are genotyped in an initial group of subjects (stage I) and only the promising markers are genotyped in additional subjects (stage II), can be used to reduce genotyping cost in a genome-wide case-control association study even after allowing for much higher per genotype costs using specially designed assays in stage II, compared to the fixed array of SNPs used in stage I. In addition, we consider the problem of using measured SNPs to make (imperfect) prediction of unmeasured SNPs for association tests of all SNPs (measured or unmeasured) genome wide and the utility of expanding genotyping densities in stage II in the regions where significant associations were detected in stage I. Under a set of reasonable but conservative assumptions, we derive optimal two-stage design configurations (sample sizes and the thresholds of significance in both stages) with these optimal designs depending both on the total number of markers tested and upon the ratios of cost in stage II versus stage I. In addition we show how existing software for power and sample size calculations can be used for the purpose of designing two-stage studies, for a wide range of assumptions about the number of markers genotyped and the costs of genotyping in each stage of the study.

Case-Control Studies↗
PubMed2005

Genome analysis of Coxiella burnetii species: insights into pathogenesis and evolution and implications for biodefense.

Coxiella burnetii, the etiological agent of Q fever, is a class B biodefense agent. We are continuing the momentum of discovery generated by the first Coxiella genome sequences by extending the breadth of genomics to include four additional heterogeneous C. burnetii strains. We are also sequencing the genome of Rickettsiella grylli, an intracellular parasite of grasshoppers and the closest known phylogenetic relative to the Coxiella group. These data will enable the investigation of fundamental questions about Coxiella pathogenicity and virulence as well as broader evolutionary questions about the transition to obligate intracellular life. Specifically, sequence comparisons will permit examination of genetic differences, allowing us to address key questions: What core genes are necessary for an obligate intracellular lifestyle and developmental cycle of the genus? What specific genetic determinants can be linked to virulence properties such as host preference, disease severity, and pathology (i.e., acute vs. chronic disease)? What are the frequencies of mutation and intragenomic recombination, and levels of genome reduction? What specific factors are relevant to colonization and virulence in human hosts (based on comparisons with R. grylli)? From a public health and biodefense perspective, exposure to different strains, either natural or due to illegitimate release, may have different outcomes. With extensive genomic-level information from diverse strains, investigators can determine effective drug and vaccine targets and design methods to accurately type Coxiella based on a subset of genes, opening the way for cost-effective targeted PCR- or antibody-based tests.

Biological Warfare↗
PubMed2006

Using linkage genome scans to improve power of association in genome scans.

Scanning the genome for association between markers and complex diseases typically requires testing hundreds of thousands of genetic polymorphisms. Testing such a large number of hypotheses exacerbates the trade-off between power to detect meaningful associations and the chance of making false discoveries. Even before the full genome is scanned, investigators often favor certain regions on the basis of the results of prior investigations, such as previous linkage scans. The remaining regions of the genome are investigated simultaneously because genotyping is relatively inexpensive compared with the cost of recruiting participants for a genetic study and because prior evidence is rarely sufficient to rule out these regions as harboring genes with variation of conferring liability (liability genes). However, the multiple testing inherent in broad genomic searches diminishes power to detect association, even for genes falling in regions of the genome favored a priori. Multiple testing problems of this nature are well suited for application of the false-discovery rate (FDR) principle, which can improve power. To enhance power further, a new FDR approach is proposed that involves weighting the hypotheses on the basis of prior data. We present a method for using linkage data to weight the association P values. Our investigations reveal that if the linkage study is informative, the procedure improves power considerably. Remarkably, the loss in power is small, even when the linkage study is uninformative. For a class of genetic models, we calculate the sample size required to obtain useful prior information from a linkage study. This inquiry reveals that, among genetic models that are seemingly equal in genetic information, some are much more promising than others for this mode of analysis.

Genetic Linkage↗
PubMed2005

Some statistical properties of regulatory DNA sequences, and their use in predicting regulatory regions in the Drosophila genome: the fluffy-tail test.

BACKGROUND: This paper addresses the problem of recognising DNA cis-regulatory modules which are located far from genes. Experimental procedures for this are slow and costly, and computational methods are hard, because they lack positional information. RESULTS: We present a novel statistical method, the "fluffy-tail test", to recognise regulatory DNA. We exploit one of the basic informational properties of regulatory DNA: abundance of over-represented transcription factor binding site (TFBS) motifs, although we do not look for specific TFBS motifs, per se . Though overrepresentation of TFBS motifs in regulatory DNA has been intensively exploited by many algorithms, it is still a difficult problem to distinguish regulatory from other genomic DNA. CONCLUSION: We show that, in the data used, our method is able to distinguish cis-regulatory modules by exploiting statistical differences between the probability distributions of similar words in regulatory and other DNA. The potential application of our method includes annotation of new genomic sequences and motif discovery.

Algorithms↗
PubMed2003

Detection of an early HIV-1 infection by HIV RNA testing in an Italian blood donor during the preseroconversion window period.

BACKGROUND: The implementation of NAT technologies for HIV screening has further reduced the diagnostic window in recent HIV infection. There is still a debate regarding the cost effectiveness of genomic screening of blood donations for transfusion-transmitted viruses (HBV, HCV, HIV). STUDY DESIGN AND METHODS: Since October 2001, at the Transfusion Service of Verona, single-donation NAT testing for HCV and HIV-1 (Procleix TMA HIV-1/HCV Assay) of all blood donations has been performed. CASE REPORT: A case of acute HIV-1 infection detected by HIV NAT in a repeat blood donor who donated during the preseroconversion window period is reported. All blood components donated were discarded, and the donor started antiretroviral therapy 2 weeks after blood donation. HIV-1 p24 antigen was still negative 10 days after the HIV-1 RNA-positive blood donation. Seroconversion was documented by Day 41 after donation. CONCLUSION: This case report testifies that HIV NAT screening of blood donation is effective in preventing the transmission of HIV infection through blood components.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Contributions of public health to genetics education for health care professionals.

With growing knowledge about the role of genetics in health, genetics education for health care professionals has taken on increasing importance. Many efforts are under way to develop new genetics curricula. Although such efforts are primarily the responsibility of health professional schools and professional societies, the public health system is an important stakeholder, and different sectors of public health have opportunities to enhance educational efforts. These include the development of authoritative information sources about the clinical utility of genetic susceptibility and pharmacogenetic tests, creation of networks that link professionals in underserved regions to educational materials and consultative backup, and sponsorship of forums for multidisciplinary discussion of controversial issues. Public health input can help to ensure an appropriate emphasis on health outcomes as new genomic tests and technologies come into use, thus helping to protect society from the social and medical costs of genetic tests with limited clinical value.

Genetic Predisposition to Disease↗
PubMed2006

Strategy for applying genome-wide selection in dairy cattle.

Animals can be genotyped for thousands of single nucleotide polymorphisms (SNPs) at one time, where the SNPs are located at roughly 1-cM intervals throughout the genome. For each contiguous pair of SNPs there are four possible haplotypes that could be inherited from the sire. The effects of each interval on a trait can be estimated for all intervals simultaneously in a model where interval effects are random factors. Given the estimated effects of each haplotype for every interval in the genome, and given an animal's genotype, a 'genomic' estimated breeding value is obtained by summing the estimated effects for that genotype. The accuracy of that estimator of breeding values is around 80%. Because the genomic estimated breeding values can be calculated at birth, and because it has a high accuracy, a strategy that utilizes these advantages was compared with a traditional progeny testing strategy under a typical Canadian-like dairy cattle situation. Costs of proving bulls were reduced by 92% and genetic change was increased by a factor of 2. Genome-wide selection may become a popular tool for genetic improvement in livestock.

Animals↗
PubMed2000

Will genome detection replace serology in blood screening for microbial agents?

The residual risk of transfusion-transmitted viral infection in developed countries is considered minimal or negligible. However, zero risk remains a strong political objective. Genomic screening for HCV, HIV and HBV represents a major advance, eliminating infectious blood donations collected during the pre-seroconversion window period, rare cases of immunosilent infections and, possibly, a large spectrum of viral variants. In Western countries, HCV RNA genomic screening started on pools of 16-400 plasma samples from individual donations. Pooling may produce false-positive and false-negative results. Individual donation testing is more suitable to blood screening but requires multiplexing, automation, and affordable cost. Because donations from individuals who are HBV DNA-negative/serologically positive, or those apparently recovered from HCV infection, may remain infectious, it is unlikely that HBsAg, anti-HCV, and anti-HIV will be discontinued when genomic screening is extended to all three viruses. HIV-1 p24 antigen may prove redundant with HIV RNA screening. Anti-HTLV-I and HTLV-II will remain more effective than genomic testing.

Antibodies, Viral↗
PubMed2001

Characterization of a minimal screening set of 172 microsatellite markers for genome-wide screens of the canine genome.

We have characterized a subset of 172 microsatellite markers from the canine map, termed 'Minimal Screening Set 1' (Canine MSS-1), which we propose be used for initial genome-wide genetic linkage studies. Three hierarchical criteria were used to select markers from the current meiotic linkage and radiation hybrid maps for MSS-1. Markers were selected that (1) provided as complete coverage as possible of the canine genome, (2) were highly informative, and (3) have been ordered in linkage groups with a high degree of statistical support. This resulting screening set spans all reported meiotic linkage and RH groups, leaving only 10 known gaps > or = 20 cM. The average polymorphic information content (PIC) value of markers tested is 0.74. Coverage estimates suggest 42% of the genome is within 5 cM of at least one marker in the minimal screening set, 77% of the genome is within 10 cM. This minimal mapping set therefore provides an efficient and cost effective way to begin screening pedigrees of interest for genetic linkage.

Animals↗
PubMed2005

Gametophytic selection in Arabidopsis thaliana supports the selective model of intron length reduction.

Why do highly expressed genes have small introns? This is an important issue, not least because it provides a testing ground to compare selectionist and neutralist models of genome evolution. Some argue that small introns are selectively favoured to reduce the costs of transcription. Alternatively, large introns might permit complex regulation, not needed for highly expressed genes. This "genome design" hypothesis evokes a regionalized model of control of expression and hence can explain why intron size covaries with intergene distance, a feature also consistent with the hypothesis that highly expressed genes cluster in genomic regions with high deletion rates. As some genes are expressed in the haploid stage and hence subject to especially strong purifying selection, the evolution of genes in Arabidopsis provides a novel testing ground to discriminate between these possibilities. Importantly, controlling for expression level, genes that are expressed in pollen have shorter introns than genes that are expressed in the sporophyte. That genes flanking pollen-expressed genes have average-sized introns and intergene distances argues against regional mutational biases and genomic design. These observations thus support the view that selection for efficiency contributes to the reduction in intron length and provide the first report of a molecular signature of strong gametophytic selection.

Arabidopsis↗