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Terminology, Concepts, and Models in Genetic Epidemiology

Genetic epidemiology brings together approaches and techniques developed in mathematical genetics and statistics, medical genetics, quantitative genetics, and epidemiology. In the 1980s, the focus was on the mapping and identification of genes where defects had large effects ...

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Genetic Distance and Markers Used in Linkage Mapping

In this chapter, we focus on maps and markers used for a linkage analysis. More detail regarding the actual linkage analysis methodology follows in Chapter 11. There are two major types of maps: genetic maps and physical maps. Genetic maps indicate the expected number of meiotic crossover events b ...

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Genome Variation: A Review of Web Resources

An enormous number of high-quality Web-based resources are now available to facilitate research into genome variation. Although identification of the most appropriate and informative resources can be challenging, a number of key sites provide links to more specialized resources t ...

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Approaches to Genetic Linkage Analysis

Genetic linkage analysis concerns the estimation of genetic distance between two or more genetic loci. In genetic epidemiology, it is predominantly used to identify, or map, a genetic locus that is associated with quantitative trait variation or, in the case of binary or discrete traits, modi ...

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The Genetic Epidemiology of Obesity: A Case Study

Obesity (OMIM #601665) is a disease where excessive stores of body fat impact negatively on health. The first law of thermodynamics dictates that energy cannot be created or destroyed so if energy is taken into the body, but not transformed to ATP for metabolic work or dissipated as heat, it will be stored ...

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Coronary Artery Disease: An Example Case Study

This chapter illustrates various general issues in genetic epidemiology in relation to coronary artery disease (CAD). This is a disease strongly influenced by environmental/lifestyle factors, such as smoking, but with substantial estimated heritability. Researchers aiming ...

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Modeling the Effect of Susceptibility Factors (HLA and PTPN22) in Rheumatoid Arthritis

Numerous genome-wide analyses on common multifactorial diseases have been recently published in providing, for each associated Single Nucleotide Polymorphism (SNP), an Odds Ratio (OR), either for one of the susceptibility variant allele versus none, or for two copies of it versus one co ...

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Epigenetic Variation

Epigenetics is a fast moving field and our understanding of epigenetic mechanisms has dramatically improved in recent decades. We present the role that epigenetics plays in genomic control in humans; the molecular basis of this control and the role that epigenetic aberrations play in the ae ...

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Copy Number Variation

Recent genetic epidemiology studies have been dominated by genome-wide association (GWA) studies using single nucleotide polymorphisms (SNPs). However, a form of structural genomic variation, termed copy number variation (CNV), is also widespread throughout the human genome, ...

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Mendelian Randomisation: A Tool for Assessing Causality in Observational Epidemiology

Detection and assessment of the effect of a modifiable risk factor on a disease with view to informing public health intervention policies are of fundamental concern in aetiological epidemiology. In order to have solid evidence that such a public health intervention has the desired effect, ...

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Advanced Methods in Twin Studies

While twin studies have been used to estimate the heritability of different traits and disorders since the beginning of the twentieth century, statistical developments over the past 20 years and more extensive and systematic data collection have greatly expanded the scope of twin studi ...

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Family-Based Association Studies

Family-based association methods are useful because they offer improved matching of controls to cases, with the result that they are not susceptible to confounding by population stratification. They also allow analysis of parent-of-origin effects and maternal–fetal interacti ...

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Candidate Gene Association Studies

Candidate gene association studies aim to establish or characterise association between the genetic �variation occurring within a specific gene or locus and a phenotype. If the phenotype is quantitative, then the effect size is often measured as the difference between the genotype spe ...

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Fine-Scale Structure of the Genome and Markers Used in Association Mapping

In this chapter, mutation (specifically single-nucleotide polymorphisms, SNPs) and recombination will be covered in more detail, and the concepts of genotype and haplotype will be reviewed. Linkage disequilibrium (LD) describes the strength of a relationship between alleles at d ...

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Single Cell RT-PCR on Mouse Embryos: A General Approach for Developmental Biology

Preimplantation development is a complicated process, which involves many genes. We have investigated the expression patterns of 17 developmentally important genes and isoforms in early mouse embryos as well as in single cells of the mouse embryo. The comparison is an excellent example ...

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RT-PCR Amplification and Cloning of Large Viral Sequences

A long reverse transcription polymerase chain reaction (LRP) protocol is described for the amplification of large RNA sequences. The amplification of near full-length hepatitis C virus (HCV) genome from serum samples is used as an example to detail each step in LRP procedure, including pri ...

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Mutagenesis of the Repeat Regions of Herpesviruses Cloned as Bacterial Artificial Chromosomes

Cloning of infectious and pathogenic herpesvirus genomes in a bacterial artificial chromosome (BAC) vector greatly facilitates genetic manipulation of their genomes. BAC-based mutagenesis strategies of viruses can advance our understanding of the viral gene functions and d ...

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Random Mutagenesis Strategies for Campylobacter and Helicobacter Species

Campylobacterand Helicobacterspecies are important pathogens in man and animals. The study of their virulence and physiology has been difficult due to the lack of tractable genetic tools, since many of the techniques established in Escherichia coliand related species were found to be ...

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Random Mutagenesis by Error-Prone PCR

In vitro selection coupled with directed evolution represents a powerful method for generating nucleic acids and proteins with desired functional properties. Creating high-quality libraries of random sequences is an important step in this process as it allows variants of individ ...

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Amplification of Orthologous Genes Using Degenerate Primers

This chapter describes the use of degenerate primers for PCR amplification of orthologous DNA from related species. While several methods for designing degenerate primers have been described, an important consideration is to base the design on a short region of highly conserved amino ac ...

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