Correction. In reference to the article "Correlations between development rates, enzyme activities, ribosomal DNA spacer-length phenotypes, and adaptation in Drosophila melanogaster" by P. D. Cluster, D. Marinkovic, R. W. Allard, and F. J. Ayala, which appeared in number 2, January 1987, of Proc. Natl. Acad. Sci. USA (84,[610][611][612][613][614], the following error should be noted. The first author's initials are correctly cited on the paper (P. D. Cluster) but are incorrect in the index (p. v) and the Contributed by R. W. Allard, September 26, 1986 ABSTRACT Selection for "fast" preadult development rate among the progeny offlies collected in a natural population of Drosophila melanogaster produced a line that developed more rapidly than a line selected for "slow" preadult development rate. Assays for enzyme activity levels showed that the activities of a-glycerophosphate dehydrogenase, alcohol dehydrogenase, and malic enzyme were higher in the fast than in the slow line, but that the activity of superoxide dismutase was lower in the fast line. Differences in the frequencies of spacerlength phenotypes of X chromosome-linked rRNA genes (rDNA), which developed between the lines during the selection process, are larger than can be explained on the basis of genetic drift alone. Long rDNA spacers had high frequency in the fast line; short spacers, in the slow line. We conclude that enzyme levels affected adaptation under the selective regimes imposed and that the different X-linked rDNA spacer-length phenotypes are either adaptive in themselves or that they mark chromosomal segments carrying genes relevant to adaptation.Interest in the role that regulatory genes play in adaptation has increased in recent years. In insects, regulatory variation for enzyme activities has frequently been found both within and among individuals (1-6); thus, for example, variation in the activity of six among seven enzymes studied has been reported to be correlated with preadult development rates in Drosophila melanogaster and Drosophila subobscura (7,8). Although allozyme variants have been implicated as sources of variation for enzyme activities (2,5,7,8) and for development rates (7-9), variation in enzyme activity has also been reported in stocks that are identical to each other for the chromosome carrying the structural locus but differ in other chromosomes, which demonstrates that regulatory genes other than structural allozymes may also be responsible for variation in enzyme activities (1, 5).rRNA gene (rDNA) mutants have been reported to be associated with retarded development in D. melanogaster (10), Drosophila hydei (11), and Drosophila mercatorum (12, 13), and it has been suggested that the slower rates of development may be due to decreased metabolic activity resulting from reduced numbers of functional rRNA genes. The transcriptional efficiency of the rDNA might also affect development rates. There is evidence that rDNA spacers may modify this transcriptional efficiency (14)(15)(16)(17)(18)(19) P.D.C., R.W.A., and A. A....

The influence of epistatic interactions of lethal and non-lethal genes upon viability of Drosophila inversion karyotypes is poorly known. In this paper we present comparative results for viabilities of 21 originally natural O-inversion homo- and 38 heterokaryotypes in a D. subobscura population. We observed strong heterotic effect in viability of O-lethal heterozygotes irrespective of different inversion backgrounds, which indicates a mechanism for protection of a great number of lethal genes. In O-non-lethal heterozygotes the heterotic effect in viability was absent irrespective of different inversion backgrounds. Our results showed a great extent of genetic load and high abundance of O-chromosomal arrangements in the population analyzed. It belongs to the set of central European populations. An epistasis of lethal genes present in O-inversion hetero- and not present in O-inversion homokaryotypes of moderate or low frequencies could be good example for co-adaptation of chromosomal inversions with regard to the genetic load. This represents a more efficient mechanism for limitation of genetic load than alternative mechanisms for protection of lethals. Except for lethal genes, possible epistatic interactions of mildly deleterious (subvital) genes, could also be responsible for limiting the extent of genetic load in natural D. subobscura populations. We demonstrated a non-random distribution of several combinations of viability classes among different O-inversion homo- and heterokaryotypes. As a consequence of that, the viabilities of the O-inversion homokaryotypes compared to heterokaryotypes were significantly higher at low frequencies than in moderate or high frequencies. This shows frequency-dependence as a mechanism of balancing selection for protection of O-chromosomal inversions in natural D. subobscura populations. In addition, the viabilities of the O-inversion homokaryotypes of lower frequency, compared to homokaryotypes of moderate or high frequency, were significantly higher. This again indicates the existence of supergene selection as another mechanism for protection of chromosomal inversions, as co-adapted complexes in natural D. subobscura populations.

Our study of genetic homozygosity degree includes an analysis of the presence, distribution, and individual combination of 20 selected genetically controlled morphophysiological traits in the group of patients ( N = 93) with congenital hip dislocation (CDH) and in control sample consisting of schoolchildren from Belgrade ( N = 200). Assuming that CDH is a genetically controlled disease, we made a hypothesis that an increased homozygosity level, as well as the changed variability among the patients, could be a population-genetic parameter for the prediction of the illness. Taking into consideration our experience, as well as the experience of numerous scientists who studied the nature of the inheritance of mono-and oligogenically controlled qualitative traits, we applied a methodology to estimate the proportion of such homozygously recessive characters (HRC-TEST). This population-genetic study did not only show statistically significant difference of the middle values of genetic homozygosity (CDH: 7.1 ± 0.2; control: 5.2 ± 0.1), but of the differences in the type of distribution too, as well as the differences in the presence of certain individual combinations of such traits. The described methodology can be used in further analyses, with hope that it can be applied as an early prognosis for decreased resistance to different diseases.The frequencies of ABO blood types in the sample of CDH patients were similar to the average value of the Serbian population, while the percentage of blood group A is slightly increased. Comparing frequencies of Rh blood groups, there is no difference between tested samples. HUMAN GENETICS* This text was submitted by the authors in English.

We have analysed the inversion polymorphism and genetic load of O-chromosomes in three populations of D. subobscura from southeastern Europe. As expected for a central populations the inversion polymorphism was extensive. In a like fashion, the genetic load, in particular the frequency of lethals, was heavy in all three populations. There were significant differences in the frequency of moderately deleterious genes. These differences in viability can be attributed to balancing selection. A comparison of these two kinds of genetic polymorphism indicates that there are differences in mean viability among different gene arrangements of O-chromosomes in the three populations. The differences observed are due to an unequal distribution of various viability classes among O-chromosome gene arrangements. We here show for the first time a specific distribution of lethal genes among these arrangements within the Palearctic distribution area of D. subobscura. The lethal allelism test showed lethals are non-randomly associated with the Ost gene arrangement. The amount of genetic load is heavy in gene arrangements with a high frequency, in comparison with the ones with a low frequency. Lethal genes may be protected in combinations of low and moderate frequency gene arrangements that harbor more lethal genes, as the Ost in the one population. Some arrangements that are less protected against recombination have a higher load than ones that are more protected against recombination. This can be taken as evidence for coadaptation.

Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial disease associated with urothelial cancer, which affects people living in the alluvial plains along the tributaries of the Danube River. Challenges of studying BEN using the epidemiological method are multiple. The natural history from exposure to occurrence of the disease may take many years. The early stages of BEN are not easily detectable clinically, as the disease is asymptomatic until a significant decline in function occurs, and even then symptoms are usually non-specific. The natural history of BEN is complex, possibly with multiple risk factors operating both at the stage of initiation of renal damage and in its progression. In BEN, genetic susceptibility is due to multiple genes of small effects, gene-gene interactions, and gene-environment interactions of complex nature that are difficult to assess with current study designs. BEN is now kidney disease of the old people, and many risk factors for disease such as smoking, alcohol consumption, obesity, and diabetes could contribute to the kidney damage. Evidence is presented that environmental rather than genetic factors play a decisive role in the etiopathogenesis of BEN. Aristolochic acid, described as a culprit of BEN in 1959, is confirmed in 2007 by the molecular biology methods. Mycotoxins and polycyclic aromatic hydrocarbons, leached from lignites and found in the vicinity of endemic settlements, deserve further investigation. Despite advances in understanding the epidemiology of BEN, more research is needed on the patterns of BEN over time and between places, and on identifying the contributions of modifiable risk factors in initiating and hastening progression of BEN in order to improve the scope for preventing BEN. Primary prevention is still at the beginning. Knowledge accumulated in the fifty years of BEN research and new data about prevention and treatment of chronic kidney disease reveal several effective methods in secondary and tertiary prevention of BEN. Genetic epidemiology could establish the relative size of the genetic effect in relation to other sources of variation in disease risk (i.e., environmental effects such as intrauterine environment, physical and chemical effects, as well as behavioral and social aspects). Public health authorities in the several countries having aristolochic acid nephropathy should take immediate measures for reducing dietary exposure of residents to Aristolochia.