No description available.

No description available.

No description available.

No description available.

The extracted eye pigments of a number of Drosophila melanogaster eye colour mutant stocks, of various combinations of such mutants, and of a number of laboratory cage populations, were measured according to a modification of the method of Ephrussi and Herold. Full-sib studies and selection experiments showed that the brown eye pigment (xanthommatin) is a character of high heritability. Allelism tests suggested that variation at loci recognised by mutations contributes to the variation in the content of both red and brown eye pigments observed in wild populations. Studies of three of the intermediates of xanthonmatin synthesis, namely tryptophan, kynurenine and 3-hydroxykynurenine at several stages of pupal development showed these to be very sensitive to mutations affecting eye colour. These intermediates are also affected by variation found in wild populations. The red and brown eye pigments of a number of white locus alleles were studied in some detail in order to examine interactions between the two pathways at the level of the products of this locus.

No description available.

To determine the ability of the P-M hybrid dysgenesis system of Drosophila melanogaster to generate mutations affecting quantitative traits, X chromosome lines were constructed in which replicates of isogenic M and P strain X chromosomes were exposed to a dysgcnic cross, a nondys-genic cross, or a control cross, and recovered in common autosomal backgrounds. Mutational heritabilities of abdominal and sternopleural bristle score were in general exceptionally high. P strain chromosomes were eight times more mutable than M strain chromosomes, and dysgcnic crosses three times more effective than nondysgenic crosses in inducing polygenic variation. However, mutational heritabilities of the bristle traits were appreciable for P strain chromosomes passed through one nondysgenic cross, and for M strain chromosomes backcrossed for seven generations to inbred P strain females. The new variation resulting from one generation of mu-tagenesis was caused by a few lines, with large effects on bristles score, and all mutations reduced bristle number. Among eight of these mutant lines and two additional mutant lines which occurred spontaneously during stock maintenance, the range of additive effects for both abdominal and sternopleural bristle scores are 2 to 9.5 bristles (1.2-5.0ap) in females, and 3.7 to 15.7 bristles (2.3-9.1<7p) in males. The effects of nine mutant chromosomes (the exception is line NDC(19)) on sternopleural bristle scores are similar and close to l.3fff, well within the wildtype range. The effects of mutants NDC(19) for both bristle traits, and lines DP(146) and DP(146)NAB for abdominal bristle scores, are extreme (2.53-5.53<7«) compared with the wildtype. This result supports the hypothesis that the distribution of effects of mutant genes on quantitative characters is highly variable, and possibly leptokurtic. The overall degree of dominance of all mutant X chromosomes suggests they are partially recessive, but the effect of line NDC(19) on abdominal bristle score appears completely recessive. Six of the mutant lines have similar low sternopleural bristle scores of about 15, are caused by allelic mutations with a map distance of approximately 24.7 cM, 4.7 cM from the cflocus. Deficiency mapping shows they are within chromosomal bands 8A4-8C6 Lines NDC(19) and DP(146) have extremely low abdominal and sternopleural bristle scores of 11.5 and 14.9, and of 10.3 and 12.5 respectively, and map closely linked to the y locus. The test of allclism and deficiency mapping indicate they are closely linked but at separate loci within chromosomal bands !B2;lB4-6 and 1B4-6;1B10, respectively, with some epistatic effects. They are apparently single mutant alleles with pleiotropic effects on both bristle traits and viability. The mutation of line NDC(19) is probably at the scute locus. In situ hybridization analysis suggests these two mutants are associated with insertion of P elements within chromosomal region 1A-1B10, but the other six mutants probably resulted from excision of P elements at the site of 8C.

Vertebrate eye development requires the coordinate specification of a number of tissues and cell interactions which produce the precisely assembled organ of the adult. Careful observations of the developing eye in a variety of organisms, in addition to detailed descriptive cataloguing of its morphogenesis have provided a number of clues to the forces which direct its development. However, the advent of molecular biology has allowed analyses of the underlying forces which drive these events on a much finer level. The purpose of this project was therefore to isolate genes which are involved in eye development or maintenance, since relatively few genes have been identified which are involved in these processes. The identification of two groups of genes which are involved in programming developmental decisions has greatly aided the understanding of events which occur at the genetic level. These genes are the homeobox containing proteins and the zinc finger proteins which contain domains which are directly involved in specific DNA interaction. Originally identified in developmental and transcription regulators, the conservation of these DNA binding domains has provided an excellent tool to isolate similar genes from a variety of species. The role of three such genes has been characterised in the mammalian eye. A gene has been isolated from a human retinal cDNA library whichcontains a number of zinc-finger motifs. The expression of this gene (<i>Rox5</i>), is detected at low levels in all tissues examined. The level of expression varies between individual tissues with maximum expression in tumour cells. In serum deprived cells, the transcription of <i>Rox5</i> and a related gene is rapidly induced approximately five fold. Based on these observations, it is proposed that this gene is a transcriptional activator, which is stimulated in response to low serum conditions in cells. It is possible that this gene is a member of the stress protein family which are rapidly induced in response to various stimuli in all cells in the body.

No description available.

Variation at codon 132 of the <i>Cervus canadensis </i>(wapiti) <i>PRNP</i> has been claimed to modulate Chronic Wasting Disease (CWD), a relatively new TSE affecting cervid species and currently the only TSE naturally affecting both captive and free-ranging populations. Codon 132 corresponds to the human codon 129 and variation at this position has been associated with TSE-related balancing selection in humans. This thesis investigated the genetic variability and selective patterns of coding and non-coding regions of <i>PRNP</i> in free-ranging populations of <i>C. Canadensis </i>and <i>C. elaphus </i>(CWD-free species closely related to wapiti) to gain a better understanding of the possible functional or disease-related forces shaping PrP genetics. The study of codon 132 genotype patterns in CWD_+VEand CWD_-VE wapiti provided no evidence for genetic modulation of CWD susceptibility, challenging previously published data. Despite this, a modulatory role of this residue in CWD incubation time, as suggested by many, is still possible. The analysis of the variability patterns in the PrP gene of the two cervid species suggested the presence of purifying selection. This was also supported by analyses aimed at identifying positively selected sites, which showed that codon 100 was the only site under positive selection throughout mammalian evolution, while the rest of the protein was under strong purifying selection. These data provide further support for the hypothesis suggesting a key cellular role for the PrP protein. The adaptive pressures driving selection at codon 100 are unknown, although they are most likely to be related to PrP function. A role for variation at this position in the interaction of the PrP protein with cell membrane translocation factors is proposed. The study provided an insight into the possible forces shaping PrP genetics and revaluated the role of variation at codon 132 in the wapiti <i>PRNP</i> gene in relation to CWD susceptibility.