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Identification of Genes from Pattern Formation, Tyrosine Kinase, and Potassium Channel Families by DNA Amplification
Alexander Kamb, Michael Weir, Bernardo Rudy, Harold Varmus and Cynthia Kenyon
Proceedings of the National Academy of Sciences of the United States of America
Vol. 86, No. 12 (Jun. 15, 1989), pp. 4372-4376
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/33692
Page Count: 5
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The study of gene family members has been aided by the isolation of related genes on the basis of DNA homology. We have adapted the polymerase chain reaction to screen animal genomes very rapidly and reliably for likely gene family members. Using conserved amino acid sequences to design degenerate oligonucleotide primers, we have shown that the genome of the nematode Caenorhabditis elegans contains sequences homologous to many Drosophila genes involved in pattern formation, including the segment polarity gene wingless (vertebrate int-1), and homeobox sequences characteristic of the Antennapedia, engrailed, and paired families. In addition, we have used this method to show that C. elegans contains at least five different sequences homologous to genes in the tyrosine kinase family. Lastly, we have isolated six potassium channel sequences from humans, a result that validates the utility of the method with large genomes and suggests that human potassium channel gene diversity may be extensive. PCR screening was used to identify and classify a wide variety of distinct sequence motifs, demonstrating its utility in the study of gene families. In addition, assuming that many of the conserved sequences derive from functional genes, these results may have considerable biological significance. First, the study indicates that C. elegans contains sequences closely related to a number of genes involved in Drosophila anteroposterior patterning. Given the genetic tractability of C. elegans and Drosophila, and the resolution with which developmental events can be observed, these organisms offer a unique opportunity to compare and contrast the ways in which similar genes are used to generate different body patterns. Similarly, these results suggest that a large family of tyrosine kinases exists in C. elegans. Thus, it may be possible to use genetic strategies to define pathways within which tyrosine kinases function to control cell growth and differentiation of individual cells. Finally, the identification of six K+ channel sequences in human DNA suggests that multiple K+ channel genes exist in humans. Studies of proteins encoded by these human sequences should reveal whether they may account for some of the functional diversity displayed by K+ channels.
Proceedings of the National Academy of Sciences of the United States of America © 1989 National Academy of Sciences