Assigning the LR
Jo-Anne Bright, Michael D. Coble in Forensic DNA Profiling, 2019
This chapter describes the assignment of the likelihood ratios (LR) to single-locus examples. It also describe the theory behind three common population genetic models and demonstrate their application. The chapter gives examples of LR calculations for profiles where peaks are the stochastic threshold and may have dropped out. It uses frequencies when referencing the sample estimate and probabilities for the population parameter. The product rule is the simplest method and assumes Hardy–Weinberg equilibrium (HWE) and linkage equilibrium (LE). HWE assumes a randomly mating population of infinite size with no selection, migration, or mutation. The Hardy–Weinberg law states that the single locus genotype probabilities may be assigned as the product of allele probabilities. The product rule implies independence of alleles within an individual and between individuals. It is likely that individuals from the same subpopulation share a common ancestor, and this is more likely for smaller subpopulations.
Genotypic traits
Daniel E. Brown in Human Biological Diversity, 2019
The genotypic traits have been frequently observed through the action of the human immune system. The discovery of the human ABO blood group by Landsteiner is usually considered the first characterization of a well understood human genotypic characteristic. Given the often-fatal consequences of sickle cell, at least until the presence of modern medical intervention, one would expect this mutation to be rare in human populations. Like sickle cell alleles, thalassemia mutations are sometimes found in fairly high frequencies in human populations, and all the populations with these high frequencies are located in areas that are/were associated with high rates of malaria. Traditionally, human biologists have examined phenotypic variation among humans and attempted to derive genetic variability that underlies the phenotypic differences. Human population genetic studies have also utilized variations in the DNA on chromosomes other than the Y chromosome.
DNA typing to identify suspects
M. Krawczka, J. Schmidtke in DNA Fingerprinting, 2020
All forensic applications of DNA typing are based on the same principle. Compound genotypes convey much more genetic information than do single-locus data, and would therefore allow a much more refined identification of individuals. The DNA is organized in chromosomes, long stretches of DNA that are wrapped in proteins and passed on to future generations almost intact. A population initially thought to represent a homogenous collection of intermarrying individuals may well turn out to be a mixture of separated sub-populations. Biological traces often contain DNA or proteins still amenable to molecular analysis, and genotypes usually present themselves in non-random relationship between parents and their offspring. Use of Bayes’ rule will be illustrated for an identification method that has been in common use long before DNA testing became feasible: the ABO blood group system. Various techniques are available for DNA typing at single loci. Thus, many polymorphisms are detected by virtue of sequence alterations at or around restriction enzyme recognition sites.
Dual daclatasvir and sofosbuvir for treatment of genotype 3 chronic hepatitis C virus infection
Published in Expert Review of Gastroenterology & Hepatology, 2016
Vinay Sundaram, Kris V. Kowdley
Chronic hepatitis C virus (HCV) infection is one of the most common etiologies of liver-related mortality throughout the world. Traditionally, therapy has been focused on pegylated interferon in combination with ribavirin, with clinical trials demonstrating that HCV genotype 1 had the lowest response rate (40–50%), while genotype 3 had an intermediate response rate (60–70%). Recently, significant advances have been made with all-oral direct-acting antiviral (DAA) therapy, which have significantly improved cure rates for HCV genotype 1. Accordingly, HCV genotype 3 is now potentially the most difficult to treat. One of the most potent DAA medications is sofosbuvir, a pan-genotypic nucleotide analogue that inhibits the NS5B polymerase of HCV. Daclatasvir, a pan-genotypic inhibitor of the HCV NS5A replication complex, was recently approved in the United States for treatment of HCV genotype 3 in conjunction with sofosbuvir. This combination may provide a powerful tool in the treatment of HCV genotype 3.
Dual sofosbuvir and ribavirin therapy for chronic hepatitis C infection
Published in Expert Review of Gastroenterology & Hepatology, 2016
L Tang, H Ward, S Kattakuzhy, E Wilson, S Kottilil
Sofosbuvir is the first pan-genotypic direct acting antiviral agent to be approved. This article provides an overview of the pharmacology of sofosbuvir and ribavirin and a comprehensive summary of the phase 2 and 3 studies supporting dual sofosbuvir and ribavirin therapy for chronic hepatitis C infection. With the production of generic formulations of sofosbuvir, we anticipate this regimen leading the first wave for widespread, IFN-free treatment and becoming first line for all genotypes (including genotype 1) for much of the world—in particular in developing and middle income countries. We discuss the continued challenges with this regimen including among patients with decompensated liver disease and post-liver transplant, and renal failure. We address concerns of emerging resistance. We also discuss the future prospects including the global uptake of sofosbuvir and ribavirin for the treatment of all genotypes.
Hepatitis B vaccine effectiveness in the face of global HBV genotype diversity
Published in Expert Review of Vaccines, 2011
Adrian Cassidy, Sally Mossman, Antonio Olivieri, Marc De Ridder, Geert Leroux-Roels
Recombinant hepatitis B vaccines are of the A2 genotype; one of ten known genotypes whose distribution varies globally. Reports of rare HBV infections in blood donors with an imbalance of non-A2 genotype HBV in vaccinated subjects have raised questions about the cross-protection afforded by HBV-A2 vaccines. Infections in HBV vaccinees were asymptomatic and transient, indicating that vaccination prevented clinical disease. Preclinical data demonstrate cross-reactivity and cross-protection by A2 vaccines against non-A2 HBV genotypes. Substantial improvements in HBV control have been demonstrated in countries with diverse genotype distribution that have introduced universal childhood HBV vaccination programs. Available data show that current HBV-A2 vaccines are highly effective in preventing infections and clinical disease caused by all known HBV genotypes.
Related Knowledge Centers
- Alleles
- Chromosome Deletion
- Gene Expression
- Major Histocompatibility Complex
- Genetic Phenomena
- Gene Dosage Compensation
- Genetic Locus