Homozygosity mapping of the locus responsible for renal tubular dysplasia of cattle on bovine Chromosome 1

Renal tubular dysplasia is a hereditary disease of Japanese black cattle showing renal failure and growth retardation with an autosomal recessive trait. In the present study, we mapped the locus responsible for the disease (RTD) by linkage analysis with an inbred paternal half-sib pedigree obtained from commercial herds. By analyzing segregation of microsatellite markers in the half-sibs, significant linkage was observed between the RTD locus and markers on bovine Chromosome (Chr) 1 with the highest lod score of 11.4. Homozygosity mapping with the inbred pedigree further defined the localization of the RTD locus in a 4-cM region between microsatellite markers BMS4003 and INRA119. Mapping of the RTD locus on bovine Chr 1 will facilitate cloning and characterization of the gene responsible for this disease. Received: 24 September 1999 / Accepted: 14 December 1999     

Depression and Anxiety Correlate Differently with Salivary Free Cortisol in the Morning in Patients with Functional Somatic Syndrome

Patients presenting with functional somatic syndrome (FSS) are common, and the symptoms are persistent and difficult to treat for doctors and costly for society. The aim of this study was to clarify the common pathophysiology of FSS, especially the relationship between hypothalamic-pituitary-adrenal (HPA) axis function and psychological characteristics of patients with FSS. The subjects were 45 patients with FSS and 29 healthy controls. Salivary free cortisol was measured in the morning, and psychological tests examining depression, anxiety and quality of life (QOL) were performed on the same day. In patients with FSS, depressive scores showed a significant negative correlation with salivary free cortisol in the morning, although in healthy controls, cortisol showed a significant positive correlation with depressive scores. In addition, the correlation between other psychological test scores and cortisol secretion in patients with FSS contrasted with that of controls. The relationship between cortisol and depression, anxiety or QOL, suggests that the HPA axis of patients with FSS is dysfunctional and does not function properly when patients with FSS are under stress. This dysfunction may explain the pathology of medically unexplained persistent symptoms of patients with FSS.     

Alignment of protein sequences using the hydrophobic core scores

Making an alignment of the amino acid sequences is an essential step in the prediction of an unknown protein structure by model building from the known structure of a protein of the same family. To improve the accuracy of the alignments, we introduced the concept of hydrophobic core scores, which restrains putting insertions/deletions in the hydrophobic core regions of the protein. Eight pairs of protein sequences were aligned by this method, and the quality of the alignments were assessed by reference to those obtained by the structural superposition. The introduction of the hydrophobic core scores derived from the knowledge of the tertiary structure of one of each pair resulted in an improvement of the accuracy of the alignments. The quality of the alignment was found to depend on the homology of the protein sequences.     

Molecular cloning, genetic mapping, and expression of the mouse Sf3b1 (SAP155) gene for the U2 snRNP component of spliceosome

SAP155, a subunit of the U2 snRNP, is essential for prespliceosome assembly and splicing catalysis of the major spliceosome. Moreover, the protein has been identified in the minor (U12-dependent) spliceosome. These facts strongly suggest that SAP155 is shared by two distinct complexes owing to its importance in the removal of any type of intron. Here we have isolated a cDNA encoding the 146-kDa mouse homolog, designated Sf3b1. The amino acid sequence of Sf3b1 is very highly conserved among homologs from Schizosaccharomyces pombe (52.4% identity) to human (99.6%), and the C-terminal 825 residues of these Sf3b1 homologs show even higher identities. This C-terminal region shows significant similarity to the PR65 subunit of protein phosphatase 2A, which is composed of 15 tandem repeats of a 39 amino acid sequence. Mouse genome analyses showed Sf3b1 to be a single-copy gene mapping to the central part of Chromosome (Chr) 1. Northern blot analysis and whole mount in situ hybridization revealed Sf3b1 to be ubiquitously expressed in a variety of adult tissues and mid-gestation embryos. Received: 14 June 2000 / Accepted: 19 October 2000