A study of the association between schizophrenia and the dopamine D3 receptor gene

A study of the genetic association between schizophrenia and aBalI polymorphism in exon 1 of the dopamine D₃ (DRD3) gene, a candidate gene for schizophrenia, was conducted. The polymorphism was examined in 91 patients whose symptoms satisfied DSM-III-R for schizophrenia and 90 controls. There were no significant differences between the groups in allele frequencies or genotype counts. Contrary to a previous report, the patients were no more likely to be homozygous than controls. Moreover, no association with the presence of illness could be demonstrated when the patients were grouped according to sex, age of onset, history of admission to psychiatric institutions or positive family history.     

Paroxysmal kinesigenic choreoathetosis locus maps to chromosome 16p11.2-q12.1

Paroxysmal kinesigenic choreoathetosis (PKC), the most frequently described type of paroxysmal dyskinesia, is characterized by recurrent, brief attacks of involuntary movements induced by sudden voluntary movements. Some patients with PKC have a history of infantile afebrile convulsions with a favorable outcome. To localize the PKC locus, we performed genomewide linkage analysis on eight Japanese families with autosomal dominant PKC. Two-point linkage analysis provided a maximum LOD score of 10.27 (recombination fraction [theta] =.00; penetrance [p] =.7) at marker D16S3081, and a maximum multipoint LOD score for a subset of markers was calculated to be 11.51 (p = 0.8) at D16S3080. Haplotype analysis defined the disease locus within a region of approximately 12.4 cM between D16S3093 and D16S416. P1-derived artificial chromosome clones containing loci D16S3093 and D16S416 were mapped, by use of FISH, to 16p11.2 and 16q12.1, respectively. Thus, in the eight families studied, the chromosomal localization of the PKC critical region (PKCR) is 16p11.2-q12.1. The PKCR overlaps with a region responsible for "infantile convulsions and paroxysmal choreoathetosis" (MIM 602066), a recently recognized clinical entity with benign infantile convulsions and nonkinesigenic paroxysmal dyskinesias.     

Sequence and functional analyses of mtDNA in a maternally inherited family with bipolar disorder and depression

Recent studies suggest that mutations/polymorphisms of mitochondrial DNA (mtDNA) are associated with neuropsychiatric diseases. We identified a patient with major depression and epilepsy. Some family members in the pedigree of the proband had bipolar disorder, depression, suicide, or psychotic disorder not otherwise specified. The mode of inheritance was compatible with maternal inheritance with low penetration. We assumed that the mental disorder in this family might be associated with maternally inherited mitochondrial DNA (mtDNA) mutation. We sequenced the entire mtDNA of the proband. Among the 34 base substitutions detected in the proband, two homoplasmic, nonsynonymous single substitutions of mtDNA, T3394C in MT-ND1 and A9115G in MT-ATP6, were suspected to cause functional impairment, because the former was reported to be disease-related and the latter is vary rare. To study the functional outcome of these substitutions, we examined mitochondrial membrane potential and the activity of mitochondrial ATP synthesis in the transmitochondrial cybrids, but no significant impairment was detected. The data did not support our hypothesis that these disorders in this family are caused by mtDNA mutation(s).     

Functional polymorphisms of HSPA5: possible association with bipolar disorder

Altered endoplasmic reticulum stress (ER) response signaling is suggested in bipolar disorder. Previously, we preliminarily reported the genetic association of HSPA5 (GRP78/BiP) with bipolar disorder. Here, we extended our analysis by increasing the number of Japanese case-control samples and NIMH Genetics Initiative bipolar trio samples (NIMH trios), and also analyzed schizophrenia samples. In Japanese, nominally significant association of one haplotype was observed in extended samples of bipolar disorder but not in schizophrenia. In NIMH trios, no association was found in total samples. However, an exploratory analysis suggested that the other haplotype was significantly over-transmitted to probands only from the paternal side. The associated haplotype in Japanese or NIMH pedigrees shared three common polymorphisms in the promotor, which was found to alter promotor activity. These findings suggested promotor polymorphisms of HSPA5 may affect the interindividual variability of ER stress response and may confer a genetic risk factor for bipolar disorder.     

Genomewide high-density SNP linkage analysis of 236 Japanese families supports the existence of schizophrenia susceptibility loci on chromosomes 1p, 14q, and 20p

The Japanese Schizophrenia Sib-Pair Linkage Group (JSSLG) is a multisite collaborative study group that was organized to create a national resource for affected sib pair (ASP) studies of schizophrenia in Japan. We used a high-density single-nucleotide–polymorphism (SNP) genotyping assay, the Illumina BeadArray linkage mapping panel (version 4) comprising 5,861 SNPs, to perform a genomewide linkage analysis of JSSLG samples comprising 236 Japanese families with 268 nonindependent ASPs with schizophrenia. All subjects were Japanese. Among these families, 122 families comprised the same subjects analyzed with short tandem repeat markers. All the probands and their siblings, with the exception of seven siblings with schizoaffective disorder, had schizophrenia. After excluding SNPs with high linkage disequilibrium, we found significant evidence of linkage of schizophrenia to chromosome 1p21.2-1p13.2 (LOD=3.39) and suggestive evidence of linkage to 14q11.2 (LOD=2.87), 14q11.2-q13.2 (LOD=2.33), and 20p12.1-p11.2 (LOD=2.33). Although linkage to these regions has received little attention, these regions are included in or partially overlap the 10 regions reported by Lewis et al. that passed the two aggregate criteria of a meta-analysis. Results of the present study—which, to our knowledge, is the first genomewide analysis of schizophrenia in ASPs of a single Asian ethnicity that is comparable to the analyses done of ASPs of European descent—indicate the existence of schizophrenia susceptibility loci that are common to different ethnic groups but that likely have different ethnicity-specific effects.     

Cytogenetic studies in a Y-to-X translocation observed in three members of one family,with evidence of infertility in male carriers

Summary A family is reported in which the mother and two sons are carriers of a Y-to-X translocation, der(X)t(X;Y) (p22;q11). All of the three carriers have short statute and disproportion of extremities, but otherwise normal phenotype. One of the sons, the propositus, has been affected with schizophrenia. Evidence was obtained that male carriers are probable sterile; both sons aged 26 and 30 years had azoospermia and the biopsied specimens of the testis had histologic pictures showing spermatogenetic arrest. The mother was H-Y weakly positive, and the normal X chromosome was inactivated in the majority of the cells analyzed. Dermatoglyphics of the three carriers were unusual and dissimilar to the features of Turner's syndrome. The clinical and cytogenetic findings in the present study are compared with those of the previously reported familial cases, and the genetic background causing phenotypic abnormalities in the male and female carriers is discussed.     

A novel extracellular protease of Vibrio mimicus that mediates maturation of an endogenous hemolysin

Vibrio mimicus, a human pathogen that causes gastroenteritis, produces an enterotoxic hemolysin as a virulence factor. The hemolysin is secreted extracellularly as an inactive protoxin and converted to a mature toxin through removal of the N‐terminal propeptide, which comprises 151 amino acid residues. In this study, a novel protease having the trypsin‐like substrate specificity was purified from the bacterial culture supernatant. The N‐terminal amino acid sequence of the purified protein was identical with putative trypsin VMD27150 of V. mimicus strain VM573. The purified protease was found to cause maturation of the protoxin by cleavage of the Arg¹⁵¹? Ser¹⁵² bond. Deletion of the protease gene resulted in increased amounts of the protoxin in the culture supernatant. In addition, expression of the hemolysin and protease genes was detected during the logarithmic growth phase. These findings indicate that the protease purified may mediate maturation of the hemolysin.

     

Reductions in water,soil and nutrient losses and pesticide pollution in agroforestry practices: a review of evidence and processes

Plant and Soil - Agroforestry systems combining trees with crops or pastures have been widely used to reduce water, soil, and nutrient losses and associated water pollution from agricultural lands...