GIGYF2 mutations are not a frequent cause of familial Parkinson`s disease

Mutations in the Grb10-interacting GYF protein 2 (GIGYF2) gene, within the PARK11 locus, have been nominated as a cause of Parkinson`s disease in Italian and French populations. By sequencing the whole GIGYF2 coding region in forty-six probands (thirty-seven Italians) with familial Parkinson`s disease compatible with an autosomal dominant inheritance, we identified no mutations. Our data add to a growing body of evidence suggesting that GIGYF2 mutations are not a frequent cause of PD. (C) 2009 Elsevier Ltd. All rights reserved.

Expression of resistance by tetraploid and diploid lucerne genotypes to Phytophthora medicaginis is not influenced by inoculum level or by temperature

Phytophthora-resistant lucerne cultivars do not always perform well under conditions of high disease pressure in the field. To determine whether resistance expression remains stable under different infection intensities, tetraploid and diploid lucerne genotypes, genotypically defined for their reactions to Phytophthora medicaginis, were clonally propagated, and the influence of different reproducible inoculum levels (0 . 5 and 5 . 0 g dry weight mycelium/kg dry weight potting mix), the period of exposure to these levels (10-60 days), and temperature (16/22 degrees C and 24/30 degrees C) on disease expression was determined in controlled environments. Generally, expression of resistance by resistant genotypes, remained stable under these conditions. Biotic (e.g. Aphanomyces eutiches) or abiotic factors other than P. medicaginis may be responsible for the poorer than expected performance under field conditions in some instances, or the percentage of resistant plants in some cultivars currently classified as resistant is insufficient to provide buffering against productivity reductions under severe epidemics. Further research is needed to clarify the situation.

Strategies for genetic model specification in the screening of genome-wide meta-analysis signals for further replication

Background Meta-analysis is increasingly being employed as a screening procedure in large-scale association studies to select promising variants for follow-up studies. However, standard methods for meta-analysis require the assumption of an underlying genetic model, which is typically unknown a priori. This drawback can introduce model misspecifications, causing power to be suboptimal, or the evaluation of multiple genetic models, which augments the number of false-positive associations, ultimately leading to waste of resources with fruitless replication studies. We used simulated meta-analyses of large genetic association studies to investigate naive strategies of genetic model specification to optimize screenings of genome-wide meta-analysis signals for further replication. Methods Different methods, meta-analytical models and strategies were compared in terms of power and type-I error. Simulations were carried out for a binary trait in a wide range of true genetic models, genome-wide thresholds, minor allele frequencies (MAFs), odds ratios and between-study heterogeneity (tau(2)). Results Among the investigated strategies, a simple Bonferroni-corrected approach that fits both multiplicative and recessive models was found to be optimal in most examined scenarios, reducing the likelihood of false discoveries and enhancing power in scenarios with small MAFs either in the presence or in absence of heterogeneity. Nonetheless, this strategy is sensitive to tau(2) whenever the susceptibility allele is common (MAF epsilon 30%), resulting in an increased number of false-positive associations compared with an analysis that considers only the multiplicative model. Conclusion Invoking a simple Bonferroni adjustment and testing for both multiplicative and recessive models is fast and an optimal strategy in large meta-analysis-based screenings. However, care must be taken when examined variants are common, where specification of a multiplicative model alone may be preferable.

A high-resolution genetic map of the familial Mediterranean fever candidate region allows identification of haplotype-sharing among ethnic groups

Familial Mediterranean fever (FMF) is a recessive disorder of inflammation caused by mutations in a gene (designated MEFV) on chromosome 16p13.3, We have recently constructed a 1-Mb cosmid contig that includes the FMF critical region. Here we show genotype data for 12 markers from our physical map, including 5 newly identified microsatellites, in FMF families. Intrafamilial recombinations placed MEFV in the similar to 285 kb between D16S468/D16S3070 and D16S3376. We observed significant linkage disequilibrium in the North African Jewish population, and historical recombinants in the founder haplotype placed MEFV between D16S3082 and D16S3373 (similar to 200 kb). In smaller panels of Iraqi Jewish, Arab, and Armenian families, there were significant allelic associations only for D16S3370 and D16S2617 among the Armenians. A sizable minority of Iraqi Jewish and Armenian carrier chromosomes appeared to be derived from the North African Jewish ancestral haplotype. We observed a unique FMF haplotype common to Iraqi Jews, Arabs, and Armenians and two other haplotypes restricted to either the Iraqi Jewish or the Armenian population. These data support the view that a few major mutations account for a large percentage of the cases of FMF and suggest that same of these mutations arose before the affected Middle Eastern populations diverged from one another. (C) 1997 Academic Press.

Hepatitis Delta virus genotype 8 infection in Northeast Brazil: Inheritance from African slaves?

Hepatitis Delta virus (HDV) is endemic worldwide, but its prevalence varies in different geographical areas. While in the Brazilian Amazon, HDV is known to be endemic and to represent a significant public health problem, few studies have assessed its prevalence in other regions in the country. This study evaluated the seroprevalence of HDV among HBsAg chronic carriers from Maranhao state, a region located in the Northeast of Brazil. Among 133 patients, 5 had anti-HD, of whom 3 had HDV RNA. HDV genotypes were characterized by Bayesian phylogenetic analysis of nucleotide sequences from the HDAg coding region. HDV-3 was identified in one patient who lives in Maranhao, but was born in Amazonas state (Western Amazon basin). Phylogenetic analysis shows that this HDV-3 sequence grouped with other HDV-3 sequences isolated in this state, which suggests that the patient probably contracted HDV infection there. Surprisingly, the other two patients were infected with HDV-8, an African genotype. These patients were born and have always lived in Urbano Santos, a rural county of Maranhao state, moreover they had never been to Africa and denied any contact with people from that continent. This is the first description of the HDV-8 in non-native African populations. This genotype may have been introduced to Brazil through the slaves brought to the country from the West Africa regions during the 16-18th centuries. Our results indicate that the need of clinical and epidemiological studies to investigate the presence of this infection in other areas in Brazil. (C) 2011 Elsevier B.V. All rights reserved.

Identification of novel mutations of the WFS1 gene in Brazilian patients with Wolfram syndrome

Objective: Wolfram syndrome (WS) is a rare, progressive, neurodegenerative disorder with an autosomal recessive pattern of inheritance. The gene for WS, WFS1, was identified on chromosome 4p16 and most WS patients carry mutations in this gene. However. some studies have provided evidence for genetic heterogeneity and the genotype-phenotype relationships are not clear. Our aim was to ascertain the spectrum of WFS1 mutations in Brazilian patients with WS and to examine the phenotype-genotype relationships in these patients. Design and methods: Clinical characterization and analyses of the WFS1. gene were performed in 27 Brazilian patients with WS from 19 families. Results: We identified 15 different mutations in the WFS1 gene in 26 patients, among which nine are novel. All mutations occurred in exon 8, except for one missense mutation which was located in exon 5. Although we did not find any clear phenotype-genotype relationship in patients with mutations in exon 8, the homozygous missense mutation in exon 5 was associated with a mild phenotype: onset of diabetes mellitus and optic atrophy during adulthood with good metabolic control being achieved with low doses of sulfonylurea Conclusions: Our data show that WFS1 is the major gene involved in WS in Brazilian patients and most mutations are concentrated in exon 8. Also, our study increases the spectrum of WFS1 mutations. Although no clear phenotype-genotype relationship was found for mutations in exon 8, a mild phenotype was associated with a homozygous missense mutation in exon 5.

Transferability and characterization of nine microsatellite markers for the tropical tree species Tabebuia roseo-alba

Microsatellite loci that were previously developed in the tropical tree Tabebuia aurea were used for the genetic analysis of Tabebuia roseo-alba populations. Nine of 10 simple sequence repeat markers were amplified, and the polymorphism was assessed in 58 individuals sampled from two stands in southeastern Brazil. All loci were polymorphic with Mendelian inheritance. The allele numbers were high, ranging from 5 to 13 in population I and 3 to 7 in population II, with means of 8.9 and 5.5, respectively. We conclude that these markers can be efficiently used for parentage and gene-flow studies.

An electron microscopic study of nickel sulfide inclusions in toughened glass

It has been known since the early sixties that nickel sulfide inclusions cause spontaneous fracture of toughened (thermally tempered) glass, but despite the considerable amount of work done on this problem in the last four decades, failures still occur in the field with regularity. In this study we have classified (by viewing through a 60x optical microscope) inclusions into two groups, which are classic and atypical nickel sulfides. The classics look like the nickel sulfide inclusions found at the initiation-of-fracture of windows that have broken spontaneously. We have compared the structure and composition of the atypical inclusions with the structure and composition of the classics. All of the classic and atypical nickel sulfide inclusions studied in this work were found to have a composition in the range of Ni52S48 to Ni48S52. Inclusions on the nickel rich side of stoichiometric NiS were found to be two-phase assemblies, and inclusions on the sulphur rich side of NiS were single phase. It had been proposed that the atypicals were passive, and of a different composition to the classics. However, we found that the difference between passive and dangerous nickel sulfide inclusions was not a difference in composition but rather a difference in the type of material in the internal pore space. The passive's had carbon char in their internal pore space, whereas the pore space of dangerous inclusions contained Na2O. The presence of Na2O and carbon char with the inclusions indicates that the formation of the inclusions results from a reaction of a nickel-rich phase with sodium sulphate and carbon. (C) 2001 Kluwer Academic Publishers.

Histological evaluation of the effectiveness of increased apical enlargement for cleaning the apical third of curved canals

P>Objective To evaluate the influence of apical size on cleaning of the apical third of curved canals prepared with rotary instruments. Methodology Forty-four mesiobuccal canals of maxillary molars teeth were instrumented to different apical sizes (30, 0.02; 35, 0.02; 40, 0.02; 45, 0.02) using a crown-down technique. After canal preparation, the apical thirds of the roots were submitted to histological processing and examination. The specimens were analysed at 40x magnification and the images were submitted to morphometric analysis with an integration grid to evaluate the percentage of debris and uninstrumented root canal walls. The action of the instruments on the root canal walls was assessed based on the surface regularity, abrupt change on the continuity of root canal walls, and partial or total pre-dentine removal. The results were statistically compared using one-way anova with post hoc Tukey test. Pearson`s correlation was performed to identify potential correlations between values. Results The percentage of uninstrumented root canal dentine was higher when apical enlargement was performed with instruments 30, 0.02 taper (55.64 +/- 4.62%) and 35, 0.02 taper (49.03 +/- 5.70%) than with instruments 40, 0.02 taper (38.08 +/- 10.44%) and 45, 0.02 taper (32.65 +/- 8.51%) (P < 0.05). More debris were observed when apical enlargement was performed with instruments 30, 0.02 taper (34.62 +/- 9.49%) and 35, 0.02 taper (25.33 +/- 7.37%) (P < 0.05). There was a significant correlation between the amount of remaining debris and the perimeter of uninstrumented root canal dentine (r = 0.9130, P < 0.001). Conclusion No apical enlargement size allowed the root canal walls to be prepared completely. Apical third cleanliness could be predicted by instrument diameter.

Identification of an apolipoprotein(e) variant associated with type III hyperlipoproteinaemia in an indigenous Australian

As a result of testing for lipid and apolipoprotein(e) (apo E) phenotype status of an indigenous Australian community, an apo E variant associated with type III hyperlipoproteinaemia has been identified. Apo E phenotype was determined by analysis of VLDL by isoelectric focusing, and genotype on DNA amplified by polymerase chain reaction, using two different restriction enzyme isotyping assays. Phenotypes and genotypes were discordant in samples from two subjects and an abnormal-sized restriction fragment was also observed in their genotyping gel patterns. DNA sequencing studies revealed this was due to a single nucleotide deletion. 3817delC, at amino acid 136 on apo E. This resulted in a new reading frame and the premature termination of the apo E protein due to a stop codon (TGA) at nucleotide 4105. The variant apo E null allele showed a recessive mode of inheritance and, in combination with the E2 allele, resulted in the type III hyperlipoproteinaemic phenotype but when inherited with the E4 allele had no marked effect on plasma lipids.

Sexual recombination in Phytophthora cinnamomi in vitro and aggressiveness of single-oospore progeny to Eucalyptus

Fifty single oospore progeny were established from an in vitro mating of A1 and A2 mating type isolates of Phytophthora cinnamomi from South Africa. Forty-nine progeny were identified as F-1 hybrids using seven random amplified polymorphic DNA (RAPD) primers, and one was a selfed isolate of the A1 mating type parent. Among the hybrid progeny, 24 and 25 were A1 and A2 mating type, respectively. Aggressiveness of progeny and parental isolates was assessed on 1-year-old seedlings of Eucalyptus smithii. The mean aggressiveness of hybrid oosporic isolates, expressed as lesion length, was significantly (P = 0.0001) lower than that of the parental isolates. No significant difference in aggressiveness of A1 and A2 mating type F-1 hybrid isolates was observed. This is the first report demonstrating sexual recombination in vitro in P. cinnamomi.

Advances in the diagnosis of primary immunodeficiency disorders in childhood

Primary immunodeficiency disorders in childhood usually present as unusual, recurrent or severe infections, symptomatic infections with organisms of low pathogenicity, or as recognizable syndromes which are known to have associated immunological abnormalities. In many of the primary immunodeficiency disorders, there are known patterns of inheritance, and other family members may be affected. Some primary immunodeficiency disorders are relatively common, such as selective IgA deficiency, and often do not lead to major morbidity. Others, such as the severe combined immune deficiency syndromes, are relatively rare, and are fatal in early life if not recognized and treated early. Diagnosis of a primary immunodeficiency disorder depends on appropriate use of laboratory investigations. Often there will be abnormalities detected on a complete blood film and measurement of immunoglobulin isotypes. More complex investigations should be undertaken in conjunction with a paediatric immunology service. In recent years, many of the clinically defined primary immunodeficiency disorders have been shown to have associated specific gene defects. For some, this has led to the identification and characterization of defective or absent gene products. The consequences of this new knowledge are more accurate diagnosis, early diagnosis including antenatal diagnosis, detection of undiagnosed disease in other family members, and the potential for new therapies including gene or gene product therapy.

Renal pathology of polycystic kidney disease and concurrent hereditary nephritis in Bull Terriers

Objective To describe the renal lesions in Bull Terrier polycystic kidney disease (BTPKD), to confirm that the renal cysts in BTPKD arise from the nephron or collecting tubule, an to identify lesions consistent with concurrent BTPKD and Bull Terrier hereditary nephritis (BTHN). Design Renal tissue from five Bull Terriers with BTPKD and eight control dogs was examined by light and transmission electron microscopy. Clinical data were collected from all dogs, and family history of BTPKD and BTHN for all Bull Terriers. Results In BTPKD the renal cysts were lined by epithelial cells of nephron or collecting duct origin that were usually squamous or cuboidal, with few organelles. They had normal junctional complexes, and basal laminae of varying thicknesses. Glomeruli with small, atrophic tufts and dilated Bowman's capsules, tubular loss and dilation, and interstitial inflammation and fibrosis were common. Whereas the lesions seen in BTHN by light microscope were nonspecific, the presence of characteristic ultrastructural glomerular basement membrane (GMB) lesions and a family history of this disease indicated concurrent BTHN was likely in three of five cases of BTPKD. Conclusion This paper provides evidence that renal cysts in BTPKD are of nephron or collecting duct origin. In addition, GBM lesions are described that strongly suggest that BTPKD and BTHN may occur simultaneously.

Remitting behaviour of Nepalese rural-to-urban migrants: Implications for theory and policy

This article uses data for Nepal to test contemporary hypotheses about the remitting behaviour and associated motives of rural-to-urban migrants and to consider the likely impact of such remittances on rural development. Possibilities for inheritance, degree of family attachment, likelihood of eventual return to place of origin and family investment in the education of the migrants are found to be significant influences on levels of remittances by Nepalese migrants. However, in Nepal, remittances do not seem to result in long-term capital investment in rural areas and so may not promote long-term development of these areas.

Development and characterization of polymorphic microsatellite markers in taro (Colocasia esculenta)

Microsatellite-containing sequences were isolated from enriched genomic libraries of taro (Colocasia esculenta (L.) Schott). The sequencing of 269 clones yielded 77 inserts containing repeat motifs. The majority of these (81.7%) were dinucleotide or trinucleotide repeats. The GT/CA repeat motif was the most common, accounting for 42% of all repeat types. From a total of 43 primer pairs designed, 41 produced markers within the expected size range. Sixteen (39%) were polymorphic when screened against a restricted set of taro genotypes from Southeast Asia and Oceania, with an average of 3.2 alleles detected on each locus. These markers represent a useful resource for taro germplasm management, genome mapping, and marker-assisted selection.