Mapping complex disease phenotypes (Genomics)

1. Introduction Complex medical conditions such as obesity and diabetes, and psychiatric disorders such as depression and schizophrenia, are common disabling diseases. Their aetiology involves genetic factors, the environment, and their interaction, with genes typically explaining half or more of the variance. A complete model of causation would include all genetic and environmental factors, and […]

Haplotype mapping (Genomics)

1. Introduction: linkage, association, and linkage disequilibrium (LD) mapping Linkage mapping is based on coinheritance of large chromosomal stretches among members of a family sharing a common phenotype. This approach has been very successful for rare Mendelian diseases, but it has led to mixed results for common diseases (Lander and Kruglyak, 1995). Many factors, such […]

YAC-STS content mapping (Genomics)

1. STS marker Sequence tagged site (STS) markers represent short unique DNA sequences for which a specific PCR (polymerase chain reaction) assay can be designed, so that any DNA sample can be easily tested for the presence or absence of this specific DNA fragment. One of the hallmarks of an STS is that it maps […]

The construction and use of radiation hybrid maps in genomic research

1. Introduction At the beginning of the sixties, Barski et al. (1960) reported the occurrence of spontaneous cellular fusion events. A few years later, new methodologies using Sendai virus inactivated by UV (Yerganian and Nell, 1966) or polyethylene glycol (PEG) treatments made it possible to induce cell fusion and to produce heterocaryotic somatic hybrid cells […]

Linkage mapping (Genomics)

1. Introduction and scope The purpose of this chapter is to provide a practical guide to linkage mapping for the identification of genes predisposing to human disease (or other interesting phenotypes). The emphasis will be on technical issues and pedigree-based analysis. More theoretical concerns, particularly those relating to methods in statistical genetics, will be covered […]

Microarray comparative genome hybridization (Genomics)

1. Introduction and history Comparative genome hybridization (CGH) is a method for genome-wide detection of chromosomal differences (see Article 11, Human cytogenetics and human chromosome abnormalities, Volume 1) between a sample and control that are due to DNA copy number changes. Briefly, total genomic DNA from a “test” and a “reference” individual are labeled with […]

Linkage disequilibrium and whole-genome association studies (Genomics)

1. Introduction Complex diseases are those that involve multiple genetic loci as well as environmental or lifestyle effects (see Article 57, Genetics of complex diseases: lessons from type 2 diabetes, Volume 2). Such diseases often affect a substantial proportion of the population. Uncovering the genetic components of such diseases is a current challenge for human […]

Fingerprint mapping (Genomics)

1. Introduction Physical maps constructed from fingerprinted clones have been widely used in genomic research, for both genome-wide and region-specific analyses. As with other clone-based physical map construction strategies, one starts with a library of randomly arrayed clones, each clone containing an unknown fragment of DNA derived from the genome of interest, and identifies experimentally […]

Restriction fragment fingerprinting software (Genomics)

1. Introduction A physical map provides an ordering of clones, markers, or both. A physical map may be built using marker-clone associations (see Article 13, YAC-STS content mapping, Volume 3), where the markers are ordered such that they are contiguous for each clone (e.g., Alizadeh et al., 1995; Soderlund and Dunham, 1995). Alternatively, a physical […]

Synteny mapping (Genomics)

Comparisons between genomes reveal homologous sequences that reflect their common evolutionary origin and subsequent conservation. Segments of DNA that have function are more likely to retain their sequence than nonfunctional segments, as they are under the constraints of natural selection during evolution. Therefore, DNA segments that are conserved between species are more likely to encode […]