Model of ammonia volatilization from calcareous soils

A quantitative model of ammonia volatilization from the calcareous soil uppermost 1-cm layer was developed and tested. The model accounts for the following processes: ammonium-ammonia equilibration in the soil solution, cation exchange between calcium and ammonium which results in ammonium distribution between soil liquid and solid phases, nitrification of dissolved ammonium, distribution of ammonia between liquid and gaseous phases and diffusion of gaseous ammonia in the soil air. The combined effect of various characteristics such as soil pH, cation exchange capacity, water capacity and nitrification rate on ammonia losses from various soil types have been studied. The model was validated against experimental results of ammonia losses from different soils for its use as a predicting tool. The model shows that most of ammonia losses can be explained by the interactive effect of high soil pH and low cation exchange capacity. Computations show increased ammonia volatilization with decreasing soil water capacity. Increasing fertilizer application rate has a small effect on percentage of ammonia losses. Increased nitrification rate and shorter “lag” period of nitrification reduce ammonia losses considerably. Good agreement was obtained between model calculations and experimental results of ammonia volatilization from 13 soils.     

The frequency of the ΔF508 mutation on cystic fibrosis chromosomes in Israeli families: correlation to CF haplotypes in Jewish communities and Arabs

Summary We have analysed the distribution of the ΔF508 mutation and the haplotypes of cystic fibrosis (CF) bearing chromosomes among the Israeli CF population. The population was classified according to its ethnic origin and included 3 groups, Ashkenazi Jews, Sephardic/Oriental Jews and Arabs. Haplotype B (KM19 allele 2, XV2c allele 1) was found to be the predominant haplotype in all groups but in each of them the haplotype distribution was different. The ΔF508 mutation was present in all groups and accounts for 32% of the CF mutations. It was mainly associated with the B haplotype but only one third of the CF chromosomes with this haplotype carry the ΔF508 mutation. This work is dedicated to Dr. Ruth Voss who initiated the CF study in Israel and was tragically killed in a car accident on 7 August 1988     

Screening for five mutations detects 97% of cystic fibrosis (CF) chromosomes and predicts a carrier frequency of 1:29 in the Jewish Ashkenazi population.

To determine the distribution and frequency of cystic fibrosis (CF) mutations in the Israeli population, we have screened 96 patients for 11 relatively common mutations. Five mutations--delta F508, G542X, W1282X, N1303K, and 3849 + 10kb C-->T--were found to account for 97% of the CF alleles in the Ashkenazi Jews. In contrast, of the 11 mutations tested, only delta F508 was detected in Jewish patients of Sephardic or Oriental origin, accounting for 43% of the CF alleles. Four mutations--delta F508, G542X, W1282X, and N1303K--accounted for 55% of the CF alleles in Arab patients. In a pilot screening study, a random sample of 424 Ashkenazi individuals was analyzed for three mutations--delta F508, W1282X, and G542X. Thirteen individuals were detected as heterozygotes (six for delta F508 and seven for W1282X), predicting a heterozygote frequency of 1:29. This is similar to the frequency of carriers in the Caucasian population of northern European ancestry. On the basis of these data, the Ashkenazi population is considered to be a candidate for CF heterozygote screening.     

The 28-kb deletion spanning D15S63 is a polymorphic variant in the Ashkenazi Jewish population

D15S63 is one of the loci, on chromosome 15q11-q13, that exhibit parent-of-origin dependent methylation and that is commonly used in the diagnosis of Prader-Willi or Angelman syndromes (PWS/AS). A 28-kb deletion spanning the D15S63 locus was identified in five unrelated patients; in each of them the deletion was inherited from a normal parent. Three of the five families segregating the deletion were reported to be of Jewish Ashkenazi ancestry, and in the other two families the ancestral origin was unknown. To determine whether the 28-kb deletion is a benign variant, we screened for the deletion in 137 unselected Ashkenazi individuals and in 268 patients who were referred for molecular diagnosis of PWS/AS, of whom 89 were Ashkenazi and 47 were of mixed origin (Ashkenazi and non-Ashkenazi Jews). In the control group, three individuals were carriers of the deletion; among the patients, three were carriers, all of whom were Ashkenazi Jews. There was no significant difference between the control group and the Ashkenazi patients, indicating that the deletion is not a cause of PWS- and AS-like syndromes. The frequency of the 28-kb deletion in the Ashkenazi population was 1/75. Since methylation analysis at the D15S63 locus may lead to misdiagnosis, we suggest the use of SNRPN, either in a PCR-based assay or as a probe in Southern hybridization, as the method of choice in the diagnosis of PWS/AS.     

Support for association of schizophrenia with genetic variation in the 6p22.3 gene,dysbindin, in sib-pair families with linkage and in an additional sample of triad families

Genetic variants in a gene on 6p22.3, dysbindin, have been shown recently to be associated with schizophrenia (Straub et al. 2002a). There is no doubt that replication in other independent samples would enhance the significance of this finding considerably. Since the gene is located in the center of the linkage peak on chromosome 6p that we reported earlier, we decided to test six of the most positive DNA polymorphisms in a sib-pair sample and in an independently ascertained sample of triads comprising 203 families, including the families for which we detected linkage on chromosome 6p. Evidence for association was observed in the two samples separately as well as in the combined sample (P=.00068 for SNP rs760761). Multilocus haplotype analysis increased the significance further to .00002 for a two-locus haplotype and to .00001 for a three-locus haplotype. Estimation of frequencies for six-locus haplotypes revealed one common haplotype with a frequency of 73.4% in transmitted, and only 57.6% in nontransmitted, parental haplotypes. All other six-locus haplotypes occurring at a frequency of >1% were less often transmitted than nontransmitted. Our results represent a first successful replication of linkage disequilibrium in psychiatric genetics detected in a region with previous evidence of linkage and will encourage the search for causes of schizophrenia by the genetic approach.     

Mutations of the mitochondrial holocytochrome c-type synthase in X-linked dominant microphthalmia with linear skin defects syndrome

The microphthalmia with linear skin defects syndrome (MLS, or MIDAS) is an X-linked dominant male-lethal disorder almost invariably associated with segmental monosomy of the Xp22 region. In two female patients, from two families, with MLS and a normal karyotype, we identified heterozygous de novo point mutations--a missense mutation (p.R217C) and a nonsense mutation (p.R197X)--in the HCCS gene. HCCS encodes the mitochondrial holocytochrome c-type synthase that functions as heme lyase by covalently adding the prosthetic heme group to both apocytochrome c and c(1). We investigated a third family, displaying phenotypic variability, in which the mother and two of her daughters carry an 8.6-kb submicroscopic deletion encompassing part of the HCCS gene. Functional analysis demonstrates that both mutant proteins (R217C and Delta 197-268) were unable to complement a Saccharomyces cerevisiae mutant deficient for the HCCS orthologue Cyc3p, in contrast to wild-type HCCS. Moreover, ectopically expressed HCCS wild-type and the R217C mutant protein are targeted to mitochondria in CHO-K1 cells, whereas the C-terminal-truncated Delta 197-268 mutant failed to be sorted to mitochondria. Cytochrome c, the final product of holocytochrome c-type synthase activity, is implicated in both oxidative phosphorylation (OXPHOS) and apoptosis. We hypothesize that the inability of HCCS-deficient cells to undergo cytochrome c-mediated apoptosis may push cell death toward necrosis that gives rise to severe deterioration of the affected tissues. In summary, we suggest that disturbance of both OXPHOS and the balance between apoptosis and necrosis, as well as the X-inactivation pattern, may contribute to the variable phenotype observed in patients with MLS.     

A reexamination of the leucine tRNAs and the leucyl-tRNA synthetase in developing Tenebrio molitor.

The translational control mechanism previously proposed for the synthesis of adult cuticular proteins in Tenebrio molitor is dependent upon the appearance of a major, novel leucine tRNA and a change in leucyl-tRNA synthetase activity just prior to adult emergence. The properties of the leucyl-tRNA synthetase extracted from pupae were reexamined. Under optimal aminoacylation conditions, no new leucine isoaccepting tRNAs were observed during development. However, under suboptimal conditions, a differential charging of the leucine tRNA species was noted. The chromatographic profiles of leucyl-tRNAs aminoacylated in vivo in both early and late pupae were found to be the same and were identical to the profiles obtained by charging tRNAs in vitro. Previous evidence for a translational control system operating in Tenebrio is discussed in relation to these results.     

Sporadic imprinting defects in Prader-Willi syndrome and Angelman syndrome: implications for imprint-switch models, genetic counseling, and prenatal diagnosis.

The Prader-Willi syndrome (PWS) and the Angelman syndrome (AS) are caused by the loss of function of imprinted genes in proximal 15q. In approximately 2%-4% of patients, this loss of function is due to an imprinting defect. In some cases, the imprinting defect is the result of a parental imprint-switch failure caused by a microdeletion of the imprinting center (IC). Here we describe the molecular analysis of 13 PWS patients and 17 AS patients who have an imprinting defect but no IC deletion. Heteroduplex and partial sequence analysis did not reveal any point mutations of the known IC elements, either. Interestingly, all of these patients represent sporadic cases, and some share the paternal (PWS) or the maternal (AS) 15q11-q13 haplotype with an unaffected sib. In each of five PWS patients informative for the grandparental origin of the incorrectly imprinted chromosome region and four cases described elsewhere, the maternally imprinted paternal chromosome region was inherited from the paternal grandmother. This suggests that the grandmaternal imprint was not erased in the father's germ line. In seven informative AS patients reported here and in three previously reported patients, the paternally imprinted maternal chromosome region was inherited from either the maternal grandfather or the maternal grandmother. The latter finding is not compatible with an imprint-switch failure, but it suggests that a paternal imprint developed either in the maternal germ line or postzygotically. We conclude (1) that the incorrect imprint in non-IC-deletion cases is the result of a spontaneous prezygotic or postzygotic error, (2) that these cases have a low recurrence risk, and (3) that the paternal imprint may be the default imprint.