In asthma, as in many other common multifactorial diseases, the identification of the susceptibility genes has been challenging because consistent results at the genome-wide significance level have been scarce. So far, genome-wide scans have been reported in 17 study populations. By m ...
The etiology of type 2 diabetes (T2D) is complex and remains poorly understood. Differences in individual susceptibility to this condition reflect the action of multiple variants, each of which confers a modest effect, and their interactions with a variety of environmental exposures. S ...
The basis for recent developments on the characterization of the linkage-disequilibrium structure of the genome and the application of association mapping to genes for common human diseases is described. Patterns of linkage disequilibrium are now understood, for a number of human po ...
The current exciting developments in association mapping are founded on theory, which has been developed since the beginning of the last century. I hereby review these developments in their historical context.
Effective application of association mapping for complex traits requires characterization of linkage disequilibrium (LD) patterns that reflect the dominant process of recombination and its duration in addition to the more subtle influences of mutation, selection, and genet ...
The precise characterization of the linkage disequilibrium (LD) landscape from highdensity single-nucleotide polymorphism (SNP) data underpins the association mapping of diseases and other studies. We describe the algorithm and implementation of a powerful approach for co ...
Natural selection has been theoretically and empirically proven to alter patterns of linkage disequilibrium (LD). Reciprocally, recombination, the driving force behind LD, modifies the signature of natural selection by reintroducing variation in a punctuate manner across the ...
The goal of the Human Genome Project and the subsequent HapMap Project was to accelerate the pace at which genes for complex human traits were discovered. Elated by the early successes from cloning disease genes for monogenic disorders, the architects of the projects reasoned that complex hum ...
The physical mapping of functional genes and polymorphic markers is obviously important for understanding genome organization in higher organisms. Fluorescence in situ hybridization of labeled DNA to metaphase chromosome spreads has been a very effective means of accomplish ...
In situ hybridization and solution-phase PCR are suitable methods for DNA or RNA analysis. The first protocol for in situ hybridization was described almost 25 years ago (1). Since then, this technique has proven valuable to localize cellular DNA or mRNA. It has also been applied to detect viral DNA or R ...
The polymerase chain reaction (PCR) is an extraordinarily powerful tool that can amplify fragments of DNA or mRNA from a single cell (1). By combining PCR with other established methods, the reaction has been extended from isolated DNA in solution, to mRNA, to studies using tissue sections (2–5). In s ...
The polymerase chain reaction (PCR) (1,2) is extremely sensitive and flexible, and in theory, will detect a single copy of a specific DNA (or retrotranscribed RNA) sequence either in cell cultures or in clinical samples (3). PCR technology has, therefore, been applied to the diagnosis of a wide range of ...
The polymerase chain reaction (PCR) has revolutionized the manner in which molecular biologists are able to examine nucleic acids by offering an extremely sensitive mechanism for amplifying specific target sequences. The combination of increased sensitivity owing to the amplif ...
In contrast to the immediate and enormous impact that solution-phase polymerase chain reaction (PCR) had in molecular biology, morphologists have regarded the development of in situ PCR with cautious expectancy (1,2). The notion of employing a PCR-based amplification step to increase ...
Primed in situ (PRINS) labeling has become an alternative to in situ hybridization (ISH) for the localization of nucleic acid sequences in cell (1–4) and tissue preparations (5; see also. Chapter 5)In the PRINS method, an unlabeled primer (restriction fragment, PCR product, or oligonucleoti ...
Primed in situ (PRINS) labeling has become an alternative to in situ hybridization (ISH) for the localization of nucleic acid sequences in cell preparations (1–4). In the PRINS method, an unlabeled primer (restriction fragment, PCR product, or oligonucleotide) is annealed to its compleme ...
Conventional PRINS (if it is possible to use such a description for a relatively new technique) is capable of identifying and quantifying chromosomes or chromosome pairs in metaphase or interphase cells (1–4). Each PRINS reaction can only identify one pair of homologous chromosomes, beca ...
One of the inherent problems with conventional fluorescent in situ hybridization (FISH) on metaphase chromosomes has been the difficulty in resolving closely associated markers. Any targets separated by less than about 1 Mb (1 � 106 bp) tend to appear as a single locus on metaphase chromosomes. ...
Primed in situ (PRINS) labeling has become an alternative to in situ hybridization (ISH) for the localization of nucleic acid sequences in cell (1–4) and tissue preparations (5; see also Chapter 5). In the PRINS method, an unlabeled primer (restriction fragment, PCR product, or oligonucleotid ...
The technique of in situ hybridization developed initially by Pardue and Gall (1) and Jones (2) can be placed on a par with Southern (3) hybridization in the enormous contribution it has given to the fields of cellular and molecular biology in eukaryotes. Initially developed for repetitive DNAs in m ...
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