reported experiments in which we were able to transfer the phenotype of tumor metastasis via transfection of DNA extracted from a human metastatic cervical adenocarcinoma. This DNA induced the conversion of recipient tumorigenic cells from a nonmetastatic to a metastatic phenotype. Moreover, we associated this change with the transfer of a specific human DNA fragment. In the intervening time, we have tried to extend and solidify these results. These conversions to a metastatic phenotype were reproduced on some occasions but not on others. As we have reported at a number of scientific meetings, the initial reported linkage to a specific DNA fragment was incorrect, and we were unable to establish a linkage with another human DNA fragment. After 3 years of continuous efforts to clarify these initial observations, we must now conclude that they do not represent a reproducible biological phenomenon. Our reported observations on the association of the ras oncogene with the metastatic phenotype remain highly reproducible in our laboratory and others. We hope that experiments of this sort will eventually lead us and others to successfully identify genetic determinants of metastasis.
Heat-denaturation studies of xanthine de-hydrogenase have revealed many more additional alleles at the locus controlling this enzyme than are revealed by electrophoretic studies. In natural populations of species in the virilis group of the genus Drosophila, heat-denaturation studies of flies from the same locality revealed 1.74 times as many alleles as did electrophoretic studies. Similarly, studies of several species over their geographic range also revealed 1.74 times as many alleles. In addition, for the nine species studied, electrophoretic analysis had revealed only 11 alleles within the group, whereas heatdenaturation studies revealed a total of 32 alleles. These findings are discussed in the light of the continuing controversy over Darwinian and non-Darwinian theories of evolution.Since the advent of electrophoretic techniques for the analysis of genetic variation in natural populations (1-3), numerous studies have confirmed and extended the original findings that a large proportion of the genome is subject to variation (4).The average insect may be heterozygous for as many as 20% of its genes, though for humans this figure may be nearer 5%.The extent to which this value is underestimated is not precisely known, but some have suggested that electrophoretic techniques overlook from 2/9 to 8/4 of the genetic variability per locus (5,6).It is widely appreciated that techniques for determination of the sequence of amino-acid residues of proteins could precisely define the amount of genetic variability at a structural gene locus. For enzymes, however, as opposed to luxury proteins such as the hemoglobins, sequencing techniques are enormously time consuming and costly. In this report we show that the simple technique of heat denaturation, performed on extracts from single adult Drosophila, discloses from two to three times as many alleles at the xanthine dehydrogenase (XDH) locus as were estimated previously. Heat denaturation has been used by others to detect differences between allozymes having different electrophoretic mobility (2, 7, 8), and Harris (9) has documented other quantitative differences in allozymes. To our knowledge, however, this is the first extensive study of heat-stability differences among allozymes sharing the same electrophoretic mobility. MATERIALS AND METHODSIn this study we used 11 members of the virilis group of Drosophila. These included material from long-established laboratory cultures as well as freshly collected strains maintained as iso-female lines. Details of these collections will be published elsewhere (10). In this report we give results from 86 lines inbred from the original stocks to obtain strains exhibiting a single electrophoretic mobility for the enzyme xanthine dehydrogenase. This enzyme was chosen for several reasons. It seems to be representative of loci so far encountered in species of the virilis group. It is moderately polymorphic, certain of its alleles are widely shared among the species of the group, and many polymorphisms are common to several speci...
The prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency and sickle cell trait was determined in 371 Cameroonian males and 668 male blood donors in Chicago. The number of males with both sickle cell trait and G6PD deficiency was significantly greater than expected (p < 0.05) in Cameroon. The number of males with both sickle cell trait and G6PD deficiency in the Chicago population also exceeded the expected number, although this was not statistically significant (p > 0.30). A young red cell population associated with the sickle cell gene leading to elevated G6PD levels in G6PD-deficient males suggests that sickle hemoglobin may exert a beneficial effect on G6PD deficiency, rather than the opposite, as had previously been proposed. These red cells may be better able to deal with oxidative stress, which can precipitate severe hemolytic disease in G6PD deficiency.
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