Comparison of GenFlex Tag array and Pyrosequencing in SNP genotyping.

With the completion of the Human Genome Project, over 2 million sequence-verified single nucleotide polymorphisms (SNPs) have been deposited in public databases. The challenge has shifted from SNP identification to high-throughput SNP genotyping. Although this has had little impact on molecular diagnostics, it provides the potential for future molecular diagnostics of complex traits to include SNP profiling.

Pilot investigations of surface parts of three closed landfills and factors affecting them.

Aftercare of closed sanitary landfills in a major environmental problem. Rehabilitation of the landfill with vegetation and reducing leachate production are two issues that must be dealt. For this reason, Finnish Environment Institute has conducted several projects on closed landfills.

Structurally and functionally important amino acids of the agonistic conformation of the human vitamin D receptor.

The crystal structures of the ligand binding domain of human vitamin D receptor (VDR) complexed with its natural ligand or the superagonists MC1288 or KH1060 have recently been reported. The crystallized ligand binding domain (LBD) of VDR, however, differs from the full-length VDR with respect to deletion of 50 amino acids between its helices 2 and 3. In this study, we investigated structurally and functionally important amino acid interactions within the ligand binding pocket of the full-length VDR in the presence of several synthetic vitamin D(3) analogs.

Fine mapping of a multiple sclerosis locus to 2.5 Mb on chromosome 17q22-q24.

Genome-wide linkage analyses performed in a Finnish study sample have identified four potential predisposing loci for multiple sclerosis (MS). Here we made an effort to restrict the wide linkage region on chromosome 17 with a dense set of 31 markers using multipoint linkage analyses and monitoring for shared marker alleles in MS chromosomes. We carried out the linkage analyses in 22 Finnish multiplex MS families originating from a regional subisolate that shows an exceptionally high prevalence of MS in order to minimize the genetic and environmental heterogeneity of the study sample.

Lymphatic endothelial reprogramming of vascular endothelial cells by the Prox-1 homeobox transcription factor.

Lymphatic vessels are essential for fluid homeostasis, immune surveillance and fat adsorption, and also serve as a major route for tumor metastasis in many types of cancer. We found that isolated human primary lymphatic and blood vascular endothelial cells (LECs and BECs, respectively) show interesting differences in gene expression relevant for their distinct functions in vivo. Although these phenotypes are stable in vitro and in vivo, overexpression of the homeobox transcription factor Prox-1 in the BECs was capable of inducing LEC-specific gene transcription in the BECs, and, surprisingly, Prox-1 suppressed the expression of approximately 40% of the BEC-specific genes.

Efficient discovery of single-nucleotide polymorphisms in coding regions of human genes.

Single nucleotide polymorphisms in protein coding regions (cSNPs) are of great interest for their effects on phenotype and potential for mapping disease genes. We have identified 5,400 novel exonic SNPs from alignments of public EST data to the draft human genome sequence, and approximately 12,000 more novel exonic SNPs from EST cluster alignments. We found 82% of the genomic-aligned SNPs and 63% of the EST-only SNPs to be detectably polymorphic in 20 Finnish DNA samples.

Chromosome 19q13 and multiple sclerosis susceptibility in Finland: a linkage and two-stage association study.

Several studies have previously provided some albeit weak evidence for linkage or association between chromosome 19q13 and multiple sclerosis (MS) susceptibility. We performed a two-stage association analysis with 19 markers spanning 7 Mb/5.5 cM of 19q13.

Correlative motions and memory effects in molecular dynamics simulations of molecules: principal components and rescaled range analysis suggest that the motions of native BPTI are more correlated than those of its mutants.

In this work MD simulations of the native bovine pancreatic trypsin inhibitor (BPTI) and 16 mutants were done in vacuum in order to study memory effects in the mutants using principal component analysis (PCA) and the rescaled range analysis (Hurst exponents). Both PCA and the rescaled range analysis support our previous proposition, based on PCA of lysozyme, that the motions of a native protein are more correlated than those of mutants. The methods are compared, the nature and applications of the rule and the role of the long-range correlations in MD time series (i.

Molecular pathogenesis of a disease: structural consequences of aspartylglucosaminuria mutations.

A deficiency of functional aspartylglucosaminidase (AGA) causes a lysosomal storage disease, aspartylglucosaminuria (AGU). The recessively inherited disease is enriched in the Finnish population, where 98% of AGU alleles contain one founder mutation, AGU(Fin). Elsewhere in the world, we and others have described 18 different sporadic AGU mutations.

Structure-function studies of new C-20 epimer pairs of vitamin D3 analogs.

A growing number of calcitriol (1alpha,25-dihydroxyvitamin D3) analogs have become available in recent years. Many of these analogs exhibit lower calcemic effects than calcitriol and inhibit cell proliferation and enhance cell differentation more efficiently than calcitriol. We have compared structure-function relationships of a series of new C-20 epimer (20-epi) vitamin D3 analogs with their natural C-20 counterparts.

A bovine dander allergen, comparative modeling, and similarities and differences in folding with related proteins.

The most important allergenic protein in cow dander and urine is Bos d 2. It is proposed to belong to the family of lipocalins, which are proteins capable of binding small hydrophobic molecules. The allergenic properties of Bos d 2 indicate an interaction between the accessible regions of the native protein and IgE.

Activation and oligomerization of aspartylglucosaminidase.

Secretory, membrane, and lysosomal proteins undergo covalent modifications and acquire their secondary and tertiary structure in the lumen of the endoplasmic reticulum (ER). In order to pass the ER quality control system and become transported to their final destinations, many of them are also assembled into oligomers. We have recently determined the three-dimensional structure of lysosomal aspartylglucosaminidase (AGA), which belongs to a newly discovered family of homologous amidohydrolases, the N-terminal nucleophile hydrolases.

The short and long forms of type XVIII collagen show clear tissue specificities in their expression and location in basement membrane zones in humans.

Two N-terminal ends of human type XVIII collagen chains have recently been identified. The two chains have different signal peptides and variant N-terminal noncollagenous NC1 domains of 493 (NC1-493) and 303 (NC1-303) amino acid residues, respectively, but share 301 residues of their NC1 domains as well as the collagenous and C-terminal noncollagenous portions of the molecule. Antibodies were produced against the NC1 region common to both human alpha1(XVIII) chain variants and against NC1 sequences specific to the long variant and were used in combination with in situ hybridization to localize this collagen in a number of human tissues.

Inhibition of proliferation and induction of differentiation of osteoblastic cells by a novel 1,25-dihydroxyvitamin D3 analog with an extensively modified side chain (CB1093).

1,25-Dihydroxyvitamin D3 (1,25D) is involved in the regulation of proliferation and differentiation of a variety of cell types including cancer cells. In recent years, numerous new vitamin D3 analogs have been developed in order to obtain favorable therapeutic properties. The effects of a new 20-epi analog, CB1093 (20-epi-22-ethoxy-23-yne-24a,26a,27a-trihomo+ ++-1alpha,25(OH)2D3), on the proliferation and differentiation of human MG-63 osteosarcoma cell line were compared here with those of the parent compound 1,25D.

Internal motions of native lysozyme are more organized than those of mutants: a principal component analysis of molecular dynamics data.

Principal component analysis (PCA) of molecular dynamics simulations of hen egg white lysozyme and its mutants indicate that even small changes in the amino acid sequence alter considerably the internal molecular motions and that the internal motions are more organized in the native enzyme than in the mutants.

Collagen XVIII is localized in sinusoids and basement membrane zones and expressed by hepatocytes and activated stellate cells in fibrotic human liver.

Type XVIII collagen is a recently discovered nonfibrillar collagen associated with basement membranes in mice and expressed at high levels in human liver. We studied the origin, distribution, and RNA levels of type XVIII collagen in normal and fibrotic human livers by in situ hybridization, immunohistochemistry, and Northern and dot blots and compared procollagen alpha1(XVIII) RNA levels with those of procollagen alpha1(IV) and laminin gamma1, the two major components of liver basement membranes. In normal liver, type XVIII collagen was heavily deposited in perisinusoidal spaces and basement membrane zones.

Complete primary structure of two variant forms of human type XVIII collagen and tissue-specific differences in the expression of the corresponding transcripts.

We report on full-length human type XVIII collagen cDNAs that encode 1516- or 1336-residue alpha 1 (XVIII) chains. The two chains have different signal peptides and variant N-terminal non-collagenous NC1 domains of 493 (NC1-493) and 303 (NC1-303) amino acid residues, respectively, but share 301 residues of their NC1 domains, a 688-residue highly interrupted collagenous portion, and a 312-residue C-terminal non-collagenous portion. Alternative splicing affecting a 43-residue stretch at the junction of the NC1 domain and the beginning of the collagenous portion was identified.

Expression of mRNAs for type I and type III procollagens in serous ovarian cystadenomas and cystadenocarcinomas.

Malignant ovarian tumors induce a strong fibro-proliferative reaction characterized by the active production of type I and type III procollagen both locally in the ovary as well as more remotely in the peritoneal cavity. Our purpose was to determine the origin of the increased collagen production observed in serous ovarian tumors with different histological grades of malignancy, ie, whether the malignant cells or the stromal fibroblasts are responsible for the synthesis of collagen fibers. We visualized the mRNAs corresponding to the pro alpha 1(I) and pro alpha 2(I) chains of type I procollagen and the pro alpha 1(III) chain of type III procollagen by in situ hybridization.

Distribution of type XV collagen transcripts in human tissue and their production by muscle cells and fibroblasts.

Type XV collagen is a recently identified member of the diverse family of collagens, its structure being characterized by extensive interruptions in the collagenous sequences. A combination of Northern blot hybridization of fetal and adult human tissues and in situ hybridization analyses of a fetus with Down's syndrome, several placentas, and adult skin were used to localize expression of its mRNAs. Northern blot analysis revealed marked expression in heart, skeletal muscle, and placenta tissues and moderate levels in the kidney and pancreas.

Changes in running speed, blood lactic acid concentration and hormone balance during sprint training performed at an altitude of 1860 metres.

The development of results of five national level sprinters (Group A) was followed up during a training period of two weeks at an altitude of 1860 m aiming at increase of strength and speed and after it. Changes in anaerobic capacity were monitored by making blood lactic acid determinations, and occurrence of any overstrain by serum testosterone, cortisol, growth hormone and SHBG (sex hormone binding globulin) determinations. A control group (Group B) trained simultaneously according to a similar programme at sea level.