Biomedical subjects

Maija Parkkonen

Publications and source records attributed to Maija Parkkonen.

5 recordsLinked to original sources

PubMed2006

Diagnosing diabetic nephropathy by 1H NMR metabonomics of serum.

OBJECT: The most severe complication of type 1 diabetes (T1DM) is diabetic nephropathy. It is associated with a high risk of cardiovascular complications and premature death and requires early detection to be efficiently treated. The clinical practice to diagnose diabetic nephropathy is also a non-optimal and tedious set up based on albumin excretion rate in multiple overnight or 24h urine samples. Conversely, in this study, these independent diagnostic data are used to provide a realistic testing case for applying (1)H NMR metabonomics of serum in a diagnostic fashion. MATERIALS AND METHODS: 182 T1DM and 21 non-diabetic (non-T1DM) individuals were studied. The (1)H NMR of serum at 500 MHz was targeted at two molecular windows: lipoprotein lipids and low-molecular-weight metabolites. RESULTS: T1DM and non-T1DM individuals were exclusively separated by (1)H NMR. For diabetic nephropathy diagnosis in the T1DM patients, (1)H NMR data (and clinical biochemistry data) gave a sensitivity of 87.1% (83.9%) and a specificity of 87.7% (95.9%). The predictive values of positive and negative tests were 89.0% (95.5%) and 83.6% (79.2%), respectively. CONCLUSIONS: (1)H NMR metabonomics clearly distinguishes metabolic characteristics of T1DM and appears approximately as good a means to diagnose diabetic nephropathy from serum as an advanced set of biochemical variables.

Biomarkers↗

PubMed2006

Association analysis of the AIRE and insulin genes in Finnish type 1 diabetic patients.

Mutations in the autoimmune regulator (AIRE) gene cause a recessive Mendelian disorder autoimmune polyendocrinopathy syndrome type 1 (APS-1 or autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy). APS-1 patients develop multiorgan autoimmune diseases including type 1 diabetes (prevalence 12%). The AIRE protein controls the central tolerance induction in the thymus by regulating the expression levels of tissue-specific peripheral antigens, such as insulin. We hypothesized that the insulin gene (INS) polymorphisms together with the AIRE variations may predispose individuals to diabetes. The role of the AIRE gene was tested both independently and on the condition of the INS risk genotype in the Finnish type 1 diabetes sample. A total of 733 type 1 diabetic cases and 735 age- and sex-matched healthy controls were used in the analysis. Five common single nucleotide polymorphisms (SNPs) in the AIRE gene were selected from the public database (dbSNP). The -23HphI polymorphism was used as a surrogate marker for the INS gene promoter repeat. The five genotyped SNPs in the AIRE gene showed no evidence of association with type 1 diabetes. As expected, the INS gene polymorphism -23HphI was significantly associated with susceptibility to type 1 diabetes (P=6.8 x 10(-12), chi(2) test). When the subclass of patients carrying the homozygote genotype of the INS gene was used in the analysis, the AIRE polymorphisms showed no association with the disease. In conclusion, the AIRE gene does not seem to contribute to disease susceptibility in Finnish type 1 diabetic patients, whereas the insulin gene represents a notable risk factor for disease in this population.

Adult↗

PubMed2006

A quality assessment survey of SNP genotyping laboratories.

To survey the quality of SNP genotyping, a joint Nordic quality assessment (QA) round was organized between 11 laboratories in the Nordic and Baltic countries. The QA round involved blinded genotyping of 47 DNA samples for 18 or six randomly selected SNPs. The methods used by the participating laboratories included all major platforms for small- to medium-size SNP genotyping. The laboratories used their standard procedures for SNP assay design, genotyping, and quality control. Based on the joint results from all laboratories, a consensus genotype for each DNA sample and SNP was determined by the coordinator of the survey, and the results from each laboratory were compared to this genotype. The overall genotyping accuracy achieved in the survey was excellent. Six laboratories delivered genotype data that were in full agreement with the consensus genotype. The average accuracy per SNP varied from 99.1 to 100% between the laboratories, and it was frequently 100% for the majority of the assays for which SNP genotypes were reported. Lessons from the survey are that special attention should be given to the quality of the DNA samples prior to genotyping, and that a conservative approach for calling the genotypes should be used to achieve a high accuracy.

Clinical Laboratory Techniques↗

PubMed2005

Fine mapping of the multiple sclerosis susceptibility locus on 5p14-p12.

Linkage analyses have identified four major MS susceptibility loci in Finns. Here we have fine mapped the region on chromosome 5p in 28 Finnish MS families. Marker D5S416 provided the highest pairwise LOD score, and multipoint and haplotype analyses restrict the critical region to about 5.3 Mb on 5p15 between markers D5S1987 and D5S416. Ascertaining for HLA type and geographical origin indicated that families with and without the HLA DR15 risk haplotype, as well as families within and outside an internal high-risk region, contributed to the linkage to 5p, implying the general significance for this locus in Finnish MS families.

Chromosome Mapping↗

PubMed2005

High-throughput pedigree drawing.

Family trees have long been a valuable visual tool for geneticists in identifying clusters of inherited traits and genotypes. As more data are collected, drawing the graphs by hand becomes impractical and, for this reason, we have developed the pedigree software CraneFoot. It can process any family graph with minimal computational cost by making a pedigree transformation that enables the use of a linear node positioning algorithm. The program is designed for automated drawing to printed media and efficient visual classification of genetically interesting families from large data sets. It also incorporates a robust pedigree topology check with detailed error messages.

Algorithms↗