Biomedical subjects

Petter Lindgren

Publications and source records attributed to Petter Lindgren.

6 recordsLinked to original sources

PubMed2006

Genome-wide linkage scan of common stroke in families from northern Sweden.

BACKGROUND AND PURPOSE: Taking advantage of low genetic variations in northern Sweden, we performed a genome-wide linkage scan to investigate the susceptibility loci for common forms of stroke. METHODS: Fifty-six families, containing multiple cases of stroke and whose data had been previously used to replicate linkage to the phosphodiesterase 4D locus on chromosome 5q, were genotyped in a genome-wide scan. Fine mapping was performed, and subsequently 53 additional families from the same region were genotyped over the candidate regions. RESULTS: Linkage calculations were performed by using 3 different disease models, from a very broad (all stroke cases defined by World Health Organization MONICA criteria) to a narrower (ischemic stroke only) stroke phenotype. With all models, nonparametric multipoint linkage analysis yielded allele-sharing log of the odds (LOD) scores >1.2 at 9 locations: 1p34, 5q13, 7q35, 9q22, 9q34, 13q32, 14q32, 18p11, and 20q13. The highest allele-sharing LOD scores were obtained on chromosomes 5q (previously reported), 1p (LOD=2.09), and 18p (LOD=2.14). Fine mapping resulted in increased allele-sharing LOD scores for chromosome 5q (previously reported) and 9q22 (LOD=1.56), but all others decreased. Combining these initial results with a subsequent analysis of 53 additional families, we obtained the highest allele-sharing LOD scores on chromosomes 5q, 13q, and 18p, although none reached the initial genome-wide allele-sharing LOD scores. CONCLUSIONS: Genetic analysis of stroke in families from northern Sweden did not identify any new major stroke loci. This indicates that multiple minor susceptibility loci in addition to the previously known locus on chromosome 5 could contribute to the disease.

Aged↗

PubMed2006

Linkage but not association of calpain-10 to type 2 diabetes replicated in northern Sweden.

We present data from a genome-wide scan identifying genetic factors conferring susceptibility to type 2 diabetes. The linkage analysis was based on 59 families from northern Sweden, consisting of a total of 129 cases of type 2 diabetes and 19 individuals with impaired glucose tolerance. Model-free linkage analysis revealed a maximum multipoint logarithm of odds score of 3.19 for D2S2987 at 267.7 cM (P=0.00058), suggesting that a gene conferring susceptibility to type 2 diabetes in the northern Swedish population resides in the 2q37 region. These data replicate, in a European population, previously identified linkage of marker loci in this region to type 2 diabetes in Mexican Americans. In contrast, no evidence in support of association to the previously identified single nucleotide polymorphisms in the calpain-10 gene was observed in a case-control cohort derived from the same population.

Adult↗

PubMed2005

Telomere length and heredity: Indications of paternal inheritance.

Cellular telomere length is linked to replicative life span. Telomere repeats are lost in peripheral blood cells in vivo by age, and women show less telomere attrition than men. Previous reports have indicated that telomere length and chromosome-specific telomere-length patterns partly are inherited. The mode of heredity has not been clarified, but a link to the X chromosome was recently suggested. We analyzed peripheral mononuclear cells from 49 unrelated families for telomere length using a real-time PCR method. Short-term cultured Epstein-Barr virus-transformed lymphoblasts from the same individuals (n = 130) were analyzed for ability to maintain telomere length and possible gender-linked inheritance. A statistically significant association between telomere lengths comparing father-son (P = 0.011, n = 20) and father-daughter (P = 0.005, n = 22) pairs was found. However, no correlation was observed between mother-daughter (P = 0.463, n = 23) or mother-son (P = 0.577, n = 18). The father-offspring correlation was highly significant (P < 0.0001), in contrast to mother-offspring (P = 0.361). Epstein-Barr virus cultures demonstrated in most cases telomere preservation inversely related to initial mononuclear cell telomere length with short telomeres displaying the most pronounced elongation. Telomere length is inherited, and evidence for a father-to-offspring heritage of this trait was obtained, whereas in vitro telomere length maintenance was found to be dependent on the initial telomere length.

Adult↗

PubMed2005

Linkage of ischemic stroke to the PDE4D region on 5q in a Swedish population.

BACKGROUND AND PURPOSE: Recent Icelandic studies have demonstrated linkage for common forms of stroke to chromosome 5q12 and association between phosphodiesterase4D (PDE4D) and ischemic stroke. Using a candidate region approach, we wanted to test the validity of these findings in a different population from northern Sweden. METHODS: A total of 56 families with 117 affected individuals were included in the linkage study. Genotyping was performed with polymorphic microsatellite markers with an average distance of 4.5 cM on chromosome 5. In the association study, 275 cases of first-ever stroke were included together with 550 matched community controls. Polymorphisms were tested individually for association of PDE4D to stroke. RESULTS: Maximum allele-sharing lod score in favor of linkage was observed at marker locus D5S424 (lod score=2.06; P=0.0010). Conditional logistic regression calculations revealed no significant association of ischemic stroke to the defined at-risk allele in PDE4D (odds ratio, 1.1; 95% confidence interval, 0.84 to 1.45). A protective effect may though be implied for 2 of the polymorphisms analyzed in PDE4D. CONCLUSIONS: Using a candidate region approach in a set of stroke families from northern Sweden, we have replicated linkage of stroke susceptibility to the PDE4D gene region on chromosome 5q. Association studies in an independent nested case-control sample from the same geographically located population suggested that different alleles confer susceptibility/protection to stroke in the Icelandic and the northern Swedish populations.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2005

Homozygosity mapping of familial glioma in Northern Sweden.

About 5% of glioma cases are familial. Most glioma families are not ascribed to the well-known glioma predisposing syndromes. One segregation analysis has supported an autosomal recessive gene in glioma families, which could be studied by homozygosity mapping. The ancestors of seven glioma families from the northern region of Sweden were traced through genealogical databases. A common ancestor and inbreeding were traced to give support to an autosomal recessive gene. Homozygosity mapping was performed with a genome-wide scan of 811 markers with linkage calculations. The families were geographically mapped to see if familial glioma was more common in northern compared with southern Sweden. Three of the seven families were remotely related. Homozygosity mapping did not reveal any allele homozygous for all three families. However, there was a geographical clustering of glioma families in the northern region of Sweden. A non-parametric analysis showed an allele-sharing LOD score of 1.05 for marker D1S196 on chromosome 1q23. Genealogical studies linking glioma families might be a tool for linkage in a small set of families. This study did not support an autosomal recessive gene, implicating a low penetrant dominant gene as a possible explanation to the glioma family clustering.

Brain Neoplasms↗

PubMed2003

A multivariate approach applied to microarray data for identification of genes with cell cycle-coupled transcription.

We have analyzed microarray data using a modeling approach based on the multivariate statistical method partial least squares (PLS) regression to identify genes with periodic fluctuations in expression levels coupled to the cell cycle in the budding yeast, Saccharomyces cerevisiae. PLS has major advantages for analyzing microarray data since it can model data sets with large numbers of variables and with few observations. A response model was derived describing the expression profile over time expected for periodically transcribed genes, and was used to identify budding yeast transcripts with similar profiles. PLS was then used to interpret the importance of the variables (genes) for the model, yielding a ranking list of how well the genes fitted the generated model. Application of an appropriate cutoff value, calculated from randomized data, allows the identification of genes whose expression appears to be synchronized with cell cycling. Our approach also provides information about the stage in the cell cycle where their transcription peaks. Three synchronized yeast cell microarray data sets were analyzed, both separately and combined. Cell cycle-coupled periodicity was suggested for 455 of the 6,178 transcripts monitored in the combined data set, at a significance level of 0.5%. Among the candidates, 85% of the known periodic transcripts were included. Analysis of the three data sets separately yielded similar ranking lists, showing that the method is robust.

Algorithms↗