Abstract
Recent advances in the field of human molecular genetics have resulted in an exponential increase in the number of disease genes isolated and characterized. The identification of these disease genes has been the result of the development of specific strategies coupled with powerful and new technologies. Pivotal to these new technologies was the discovery and refinement of the polymerase chain reaction (PCR), and its application to linkage studies, mutation screening, and clone isolation. Mendelian Inheritance in Man lists all the known inherited human disorders and the defective genes associated with them, and to date there are 6000 traits listed (1) Most of the genes identified are those responsible for single-gene disorders. The more common and complex “disease-genes” to identify are those that act in combination to cause disease. These multigene diseases are called polygenic or multifactorial. In view of the advances made in the study of single-gene disorders, there is justifiable optimism that new methods in statistical analysis and laboratory methodologies will be developed to tackle this new challenge. An important stage in any cloning strategy is the generation of candidate clones. This stage is the end-point of one of four optional strategies:
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Positional cloning (PC), based on knowing nothing except subchromosomal location of the disease gene.
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Cloning based on an aspect of deduced or known function (CFK), dependent on the gene product being known or a functional assay being available.
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Cloning based on suggested animal homologues (CAH) or gene family similarities and independent of subchromosomal location.
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Cloning based on database searches (CDS) and known chromosomal location of the disease (“positional candidate”). The positional candidate approach, is becoming increasingly important as more human genes are being mapped to specific chromosomal locations.
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Rowe, P.S.N. (2000). Finding Mutations in Disease Genes. In: Econs, M.J. (eds) The Genetics of Osteoporosis and Metabolic Bone Disease. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-033-9_22
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DOI: https://doi.org/10.1007/978-1-59259-033-9_22
Publisher Name: Humana Press, Totowa, NJ
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