Biomedical subjects

K L Ayres

Publications and source records attributed to K L Ayres.

7 recordsLinked to original sources

PubMed2001

Short tandem repeat profiling provides an international reference standard for human cell lines.

Cross-contamination between cell lines is a longstanding and frequent cause of scientific misrepresentation. Estimates from national testing services indicate that up to 36% of cell lines are of a different origin or species to that claimed. To test a standard method of cell line authentication, 253 human cell lines from banks and research institutes worldwide were analyzed by short tandem repeat profiling. The short tandem repeat profile is a simple numerical code that is reproducible between laboratories, is inexpensive, and can provide an international reference standard for every cell line. If DNA profiling of cell lines is accepted and demanded internationally, scientific misrepresentation because of cross-contamination can be largely eliminated.

Cell Line↗

PubMed2001

Lipoprotein (a) as a predictor of myocardial infarction in middle-aged men.

PURPOSE: Whether serum lipoprotein (a) [Lp(a)] levels are an independent risk factor for coronary heart disease has been controversial. We have investigated its status in a prospective population survey, the Second Northwick Park Heart Study. METHODS: We recruited 2,616 men 50 to 61 years old from nine primary care practices in the United Kingdom. Baseline serum Lp(a) levels were measured by enzyme-linked immunosorbent assay (ELISA) and were analyzed in 3 groups (<25th percentile, 25th to 75th percentile, and >75th percentile) to overcome the problem of some measurements falling below the threshold of the assay. Coronary end points included sudden cardiac death, acute myocardial infarction, silent myocardial infarction on the electrocardiogram, and coronary artery bypass surgery. RESULTS: During a mean of 6 years of follow-up, 121 men had coronary events. In a multivariate analysis that also adjusted for fibrinogen, Apo-A1, Apo-B, and triglyceride levels, we identified several independent risk factors for coronary events, including cholesterol level (hazard ratio [HR] = 1.5 per SD 95% confidence interval [CI] 1.3 to 1.8), diabetes (HR = 4.1, 95% CI: 2. 0 to 8.4), current versus never smoking (HR = 2.5, 95% CI: 1.5 to 4.1), diastolic blood pressure (HR = 1.4 per SD, 95% CI: 1.1 to 1.7), Apo-A1 (HR = 0.8 per SD, 95% CI: 0.6 to 0.9), age (HR = 1.3 per SD, 95% CI: 1.1 to 1.6), and Lp(a) (>26.3 mg/dL [75th percentile] versus <2.9 mg/dL [25th percentile], HR = 1.9, 95% CI: 1.1 to 3.3]. There was a statistically significant (P = 0.01) difference in risk between the three levels of Lp(a). CONCLUSIONS: We found that a high Lp(a) level was an independent predictor of the development of coronary heart disease in middle-aged men.

Apolipoprotein A-I↗

PubMed2001

Measuring gametic disequilibrium from multilocus data.

We describe a Bayesian approach to analyzing multilocus genotype or haplotype data to assess departures from gametic (linkage) equilibrium. Our approach employs a Markov chain Monte Carlo (MCMC) algorithm to approximate the posterior probability distributions of disequilibrium parameters. The distributions are computed exactly in some simple settings. Among other advantages, posterior distributions can be presented visually, which allows the uncertainties in parameter estimates to be readily assessed. In addition, background knowledge can be incorporated, where available, to improve the precision of inferences. The method is illustrated by application to previously published datasets; implications for multilocus forensic match probabilities and for simple association-based gene mapping are also discussed.

Algorithms↗

PubMed2000

Relatedness testing in subdivided populations.

Assigning probabilities to alleged relationships, given DNA profiles, requires, among other things, calculation of a likelihood ratio (LR). Such calculations usually assume independence of genes: this assumption is not appropriate when the tested individuals share recent ancestry due to population substructure. Adjusted LR formulae, incorporating the coancestry coefficient F(ST), are presented here for various two-person relationships, and the issue of mutations in parentage testing is also addressed.

Family↗

PubMed2000

A two-locus forensic match probability for subdivided populations.

A two-locus match probability is presented that incorporates the effects of within-subpopulation inbreeding (consanguinity) in addition to population subdivision. The usual practice of calculating multi-locus match probabilities as the product of single-locus probabilities assumes independence between loci. There are a number of population genetics phenomena that can violate this assumption: in addition to consanguinity, which increases homozygosity at all loci simultaneously, gametic disequilibrium will introduce dependence into DNA profiles. However, in forensics the latter problem is usually addressed in part by the careful choice of unlinked loci. Hence, as is conventional, we assume gametic equilibrium here, and focus instead on between-locus dependence due to consanguinity. The resulting match probability formulae are an extension of existing methods in the literature, and are shown to be more conservative than these methods in the case of double homozygote matches. For two-locus profiles involving one or more heterozygous genotypes, results are similar to, or smaller than, the existing approaches.

Alleles↗

PubMed1999

Validation of short tandem repeat analysis for the investigation of cases of disputed paternity.

This study details validation of two separate multiplex STR systems for use in paternity investigations. These are the Second Generation Multiplex (SGM) developed by the UK Forensic Science Service and the PowerPlex 1 multiplex commercially available from Promega Inc. (Madison, WI, USA). These multiplexes contain 12 different STR systems (two are duplicated in the two systems). Population databases from Caucasian, Asian and Afro-Caribbean populations have been compiled for all loci. In all but two of the 36 STR/ethnic group combinations, no evidence was obtained to indicate inconsistency with Hardy-Weinberg (HW) proportions. Empirical and theoretical approaches have been taken to validate these systems for paternity testing. Samples from 121 cases of disputed paternity were analysed using established Single Locus Probe (SLP) tests currently in use, and also using the two multiplex STR systems. Results of all three test systems were compared and no non-conformities in the conclusions were observed, although four examples of apparent germ line mutations in the STR systems were identified. The data was analysed to give information on expected paternity indices and exclusion rates for these STR systems. The 12 systems combined comprise a highly discriminating test suitable for paternity testing. 99.96% of non-fathers are excluded from paternity on two or more STR systems. Where no exclusion is found, Paternity Index (PI) values of > 10,000 are expected in > 96% of cases.

Asian People↗

PubMed1998

Measuring departures from Hardy-Weinberg: a Markov chain Monte Carlo method for estimating the inbreeding coefficient.

Many well-established statistical methods in genetics were developed in a climate of severe constraints on computational power. Recent advances in simulation methodology now bring modern, flexible statistical methods within the reach of scientists having access to a desktop workstation. We illustrate the potential advantages now available by considering the problem of assessing departures from Hardy-Weinberg (HW) equilibrium. Several hypothesis tests of HW have been established, as well as a variety of point estimation methods for the parameter which measures departures from HW under the inbreeding model. We propose a computational, Bayesian method for assessing departures from HW, which has a number of important advantages over existing approaches. The method incorporates the effects-of uncertainty about the nuisance parameters--the allele frequencies--as well as the boundary constraints on f (which are functions of the nuisance parameters). Results are naturally presented visually, exploiting the graphics capabilities of modern computer environments to allow straightforward interpretation. Perhaps most importantly, the method is founded on a flexible, likelihood-based modelling framework, which can incorporate the inbreeding model if appropriate, but also allows the assumptions of the model to he investigated and, if necessary, relaxed. Under appropriate conditions, information can be shared across loci and, possibly, across populations, leading to more precise estimation. The advantages of the method are illustrated by application both to simulated data and to data analysed by alternative methods in the recent literature.

Algorithms↗