Uridine monophosphate kinase polymorphism in two Venezuelan populations.

A study of the uridine monophosphate kinase (UMPK) electrophoretic patterns in Venezuelan individuals from the mestizo population of Caracas and from the Warao Indians of the Nabasanuka village in the Delta of the Orinoco River are reported. Among the mestizo population, the frequency of the UMPK1, UMPK2, and UMPK3 alleles was .979, .020, and .001, respectively. A higher frequency of the UMPK3 gene was seen in the highly inbred Warao Indians than any other population studied to date.     

Pseudodeficiency of arylsulfatase A: a common genetic polymorphism with possible disease implications

Summary The distribution and frequency of aphidicolin-induced common fragile sites were studied in chromosomes of cultured skin fibroblasts and PHA-stimulated lymphocytes from five normal individuals; 0.2 M aphidicolin was added for the last 26 h of culture. Skin fibroblasts from five fra(X)-positive patients were also studied in the same manner. Fragile sites most frequently found in fibroblasts from normal individuals were 3q26.2, 7q11.23, 16q23, 1p31, 10q11.2, 12q23 and 7q31, whereas those in lymphocytes from the same individuals were 3p14, 16q23, Xp22, 7q32 and 14q24. The distribution of fragile sites in fibroblasts from fra(X)-positive patients was essentially identical with that in normal individuals. The average number of gaps and breaks in 100 metaphases was 36.8 in fibroblasts from normal individuals, 113.8 in those from fra(X)-positive patients, and 279 in lymphocytes from normal individuals. Their rates of chromosome-type breaks and gaps were 7.9%, 29.7% and 54.5%, respectively. Thus, the distribution and frequency of aphidicolin-induced fragile sites were different between skin fibroblasts and lymphocytes, possibly reflecting differences in their DNA replication sequence or gene activity.     

Electrophoretic variation in human serum ceruloplasmin: A new genetic polymorphism

Through the application of a specific oxidase stain to results of starch gel electrophoresis of human serum, three different electrophoretic forms of ceruloplasmin—denoted CpA (fast), CpB (intermediate), and CpC (slow)—have been defined. The electrophoretic differences are small and were first recognized through a rare variant individual who had only the fast and slow forms. Five phenotypes displaying different combinations of the three electrophoretic forms have been defined in American Negroes; these are called CpA, CpAB, CpB, CpAC, and CpBC. Twin, family, and population studies have yielded evidence indicating that the A and B electrophoretic forms are controlled by a pair of autosomal codominant alleles, designated Cp ^A and Cp ^B , and suggesting that the C form may be determined by a third allele, Cp ^C , at the same locus. The variants constitute a genetic polymorphism in American Negroes, but occur only rarely in Caucasians.Supported by U.S. Atomic Energy Commission Contract AT(11-1)-1552, by U.S. Public Health Service Research Grants AM 09381 and HD 02083, and by U.S. Public Health Service Career Development Awards 6-K3-HE-24, 980 (DCS) and 1-K3-A-7959 (GJB).     

Cytidine deaminase: a new genetic polymorphism demonstrated in human granulocytes.

Cytidine deaminase in human white blood cells has three electrophoretic phenotypes representing the homozygous and heterozygous expression of two common alleles, CDA1 and CDA2, at an autosomal locus. To explain the multibanded pattern of the heterozygote, the enzyme is assumed to have a tetrameric structure.     

The polymorphism of red cell uridine monophosphate kinase in two samples of the Italian population.

Red cell uridine monophosphate kinase polymorphism has been studied on a total of 915 individuals from two different areas of Italy (Milan and Rome). The two groups of about the same size show very similar gene frequencies. The UMPK2 allele in the pooled sample has a frequency of 2.8% which is significantly lower than those observed in the two other Caucasian populations so far examined.     

Balanced reciprocal translocation mosaicism: clinical implications. Two new cases.

Two new cases of balanced reciprocal translocation mosaicism (BRTM) are described, one with early miscarriages and a polymalformed child and the second showing an abnormal phenotype resembling the three cases previously reported in literature. The frequency of this aberration in the population referred to in our laboratory is determined and compared with previous publications.     

Activation of rat liver pyrimidine nucleoside monophosphate kinase.

The activity of the pyrimidine nucleoside monophosphate kinase (ATP:dCMP phosphotransferase, EC 2.7.4.14) from rat liver is dependent upon the presence of sulfhydryl-reducing agents. Addition to the inactive enzyme of 2-mercaptoethanol (5 mM), a reagent specific for cleavage of disulfide bonds, effects a reduction in molecular weight from approx. 53 000 to 17 000, measured by molecular sieve chromatography. This low molecular weight form is partially active in the presence of 2-mercaptoethanol (f mM). In absence of 2-mercaptoethanol, the low molecular weight form is inactive. Higher concentrations of 2-mercaptoethanol (50 mM) fully reactivate the CMP(ATP) kinase activity followed by dCMP(ATP) and CMP(dCTP) kinase activities in a sequential manner, without further change in moelcular weight. Alkylation by iodoacetamide of the enzyme at different stages of reactivation in dithiothreitol suggests an ordered appearance of the various enzyme activities. Furthermore, iodoacetamide inactivates the fully active enzyme. Thioredoxin was found to activate the enzyme in a manner similar to 2-mercaptoethanol and dithiothreitol. These results are consistent with the interpretation that the mechanism of activation of the enzyme involves cleavage of inter- and intramolecular disulfide bonds.     

Uridine kinase activities in developing, adult and neoplastic rat tissues.

Uridine kinase activities were found chiefly in the soluble fractions of rat tissues. In normal adults the activities ranged from 13 munits/g in skeletal muscle to 178 munits/g in colon. Enzyme activities in several rat neoplasms were significantly higher (e.g. in a fibrosarcoma, mammary carcinoma, renal carcinoma, pancreatic carcinoma and lymphocytic lymphoma, but not in a fast-growing Morris hepatoma). The activities were not related to tumour growth rates or sizes. In normal foetal liver, lung, brain, heart and kidney, uridine kinase concentrations equalled or exceeded those in the adult homologous tissue, but maximal activities in liver were reached 3--5 days post partum. In suckling rats the intestinal activity decreased substantially immediately after birth and normally did not rise again until late in the third postnatal week. Premature upsurges could be evoked by an injection of cortisol or by starvation of the pups overnight. Pancreatic activity was absent from 1-day-old rats, and only about 5% of the adult activity was reached by day 20; adult activities were attained rapidly after weaning. In pancreas, precocious formation or uridine kinase was elicited by overnight starvation of 2-week-old rats.     

A multilocus model of the genetic architecture of autoimmune thyroid disorder, with clinical implications

We report here a preliminary model of the genetic architecture of Autoimmune Thyroid Disorder (AITD). Using a flexible class of mathematical modeling techniques, applied to an established set of data and supplemented with information both from candidate-gene and genome-wide-association studies and from basic bioinformatics, we find strong statistical support for a model in which AITD is the result of "hits" along three distinct genetic pathways: affected individuals have (1) a genetic susceptibility to clinical AITD, along with (2) a separate predisposition to develop the autoantibodies characteristic of AITD, and they also have (3) a predisposition to develop high levels of autoantibodies once they occur. Genes underlying each of these factors then appear to interact with one another to cause clinical AITD. We also find that a genetic variant in CTLA4 that increases risk for AITD in some people might actually protect against AITD in others, depending on which additional risk variants an individual carries. Our data show that the use of statistical methods for the incorporation of information from multiple sources, combined with careful modeling of distinct intermediate phenotypes, can provide insights into the genetic architecture of complex diseases. This model has several clinical implications, which we believe will prove relevant to other complex diseases as well.     

Dexhowardia tetraspora: A new hyphomycete with possible basidiomycete affinity

Dexhowardia tetraspora gen. et sp. nov. was isolated as a contaminant in a culture received asSporotrichum aureum. It produces conidiophores which resemble those infrequently observed in conidial states ofFomitopsis annosus andF. insularis. Because it entirely lacks ampullate conidiophores, it cannot be considered congeneric withOedocephalum glomerulosum. A perfect state is unknown.

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Zusammenfassung Dexhowardia tetraspora gen. et sp. nov. war als ein Kontaminant in einer Kultur die alsSporotrichum aureum erhalten worden ist, isoliert. Sie bringt Konidiophoren hervor, die denen ähnlich sind, wie man sie in der Konidialform vonFomitopsis annosus undF. insularis selten beobachtet. Da sie blasenförmige Konidiophoren völlig missen läßt, kann sie mitOedocephalum glomerulosum nicht als congenerisch betrachtet werden. Status perfectus ist unbekannt.