The bithorax complex (BX-C) in Drosophila is a model system for studying how genes regulate growth and development. The complex spans over 300 kilobases of DNA and comprises at least nine genes that regulate other genes outside the complex to program much of the development of the thorax and abdomen of the organism. The broad objectives are (1) to determine how the individual genes of the complex are themselves regulated such that they become expressed along the body axis in an order that parallels their order in the chromosome; and (2) to understand the basis of the phenomenon of transvection (or pairing-dependent complementation) that involves an apparent coupling of cis- and trans-regulation. The specific goals are: (1) to identify as many as possible of the specific morphogenetic functions controlled by the BX-C genes and to correlate those functions with the genetic and molecular maps of the complex; [a new methodology, which uses X rays to derive transvection-suppressing rearrangements (TSRs), permits saturating the complex with chromosomal breakages that are unselected with respect to whether they do not or do not contain a mutant lesion in any of the BX-C genes; (2) to analyze regulation, especially in cis, of the BX-C genes themselves, by studying the conditions underlying the cis-inactivation (CIN) and cis-overexpression COE phenomena; (3) to identify the type of DNA-rearrangement involved in the Transabdominal mutant which results in misregulation of one or more genes located distally in the BX-C; and (4) to determine the extent to which transvection occurs throughout the entire complex and the specific conditions which promote or suppress transvection. Health-relatedness: (1) probes derived from portions of the BX-C might be able to identify within the human genome homeotic genes responsible for many types of congenital malformations such as gonadal dysgenesis, and (2) the molecular analysis of the Transabdominal mutant may uncover an important mechanism underlying the induction of certain types of benign tumors that depend upon misregulation of homeotic genes.
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