Linkage analysis of autopsy-confirmed familial Alzheimer disease supports an Alzheimer disease locus in 8q24.

Background/aims: We have previously reported the results of an extended genome-wide scan of Swedish Alzheimer disease (AD)-affected families; in this paper, we analyzed a subset of these families with autopsy-confirmed AD.

Methods: We report the fine-mapping, using both microsatellite markers and single-nucleotide polymorphisms (SNPs), in the observed maximum logarithm of the odds (LOD)-2 unit (LOD(max)-2) region under the identified linkage peak, linkage analysis of the fine-mapping data with additionally analyzed pedigrees, and association analysis of SNPs selected from candidate genes in the linked interval. The subset was made on the criterion of at least one autopsy-confirmed AD case per family, resulting in 24 families.

Linkage to the 8p21.1 region Including the CLU gene in age at onset stratified alzheimer's disease families.

Two powerful genome-wide association studies have recently reported significant association between sporadic late-onset Alzheimer's disease (AD) and markers at the CLU locus in chromosome 8p. In this study, we have stratified our previously analyzed 109 Swedish AD families according to range in age at onset and performed whole-genome linkage analysis and subsequent fine-mapping in 8p21. The subgroup analyzed in the fine-mapping consisted of 28 families with AD, having a within-family onset-range not exceeding 8 years and an age at onset between 49 ≤ 70 years.

Linkage to 20p13 including the ANGPT4 gene in families with mixed Alzheimer's disease and vascular dementia.

This study aimed at identifying novel susceptibility genes for a mixed phenotype of Alzheimer's disease and vascular dementia. Results from a genome scan showed strongest linkage to 20p13 in 18 families, and subsequent fine mapping was performed with both microsatellites and single-nucleotide polymorphisms in 18 selected candidate transcripts in an extended sample set of 30 families. The multipoint linkage peak was located at marker rs2144151 in the ANGPT4 gene, which is a strong candidate gene for vascular disease because of its involvement in angiogenesis.

Brain-derived neurotrophic factor gene variation influences cerebrospinal fluid 3-methoxy-4-hydroxyphenylglycol concentrations in healthy volunteers.

Brain-derived neurotrophic factor (BDNF) has been shown to influence monoamine transmitter synthesis, metabolism and release. We investigated possible relationships between four BDNF gene polymorphisms and cerebrospinal fluid (CSF) concentrations of 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) in healthy volunteers (n = 132). All BDNF polymorphisms (270 C/T, -633 T/A, Val66Met, and 11757 G/C) were associated with MHPG (P < 0.

Expanded high-resolution genetic study of 109 Swedish families with Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disease that affects approximately 20 million persons all over the world. There are both sporadic and familial forms of AD. We have previously reported a genome-wide linkage analysis on 71 Swedish AD families using 365 genotyped microsatellite markers.

The use of grid computing to drive data-intensive genetic research.

In genetics, with increasing data sizes and more advanced algorithms for mining complex data, a point is reached where increased computational capacity or alternative solutions becomes unavoidable. Most contemporary methods for linkage analysis are based on the Lander-Green hidden Markov model (HMM), which scales exponentially with the number of pedigree members. In whole genome linkage analysis, genotype simulations become prohibitively time consuming to perform on single computers.

Potential genetic variants in schizophrenia: a Bayesian analysis.

A number of different gene polymorphisms have been found to dispose for the development of schizophrenia. However, no single gene polymorphism is sufficient for the precipitation of schizophrenia. Swedish psychosis patients (n=103) and control subjects (n=89) were analyzed for 36 single nucleotide polymorphisms in 30 candidate genes for schizophrenia.

Brain-derived neurotrophic factor gene (BDNF) variants and schizophrenia: an association study.

Polymorphisms in the brain-derived neurotrophic factor (BDNF) gene have been suggested to be associated with schizophrenia. In a replication attempt, Swedish patients with schizophrenia (n=187) and control subjects (n=275) were assessed for four BDNF gene polymorphisms. There were no significantly different allele, genotype or haplotype frequencies between cases or controls.

Correlation between cag pathogenicity island composition and Helicobacter pylori-associated gastroduodenal disease.

Helicobacter pylori infection is associated with a variety of outcomes ranging from seemingly asymptomatic coexistence to peptic ulcer disease and gastric cancer. The cag pathogenicity island (PAI) contains genes associated with a more aggressive phenotype and has been suggested to be a determinant of severe disease outcome. The cagA gene has served as a marker for the cag PAI.

Dopamine D2 receptor gene Ser311Cys variant and schizophrenia: association study and meta-analysis.

An association has been reported between a dopamine D(2) receptor gene (DRD2) Ser311Cys variant and schizophrenia. In a replication attempt, Swedish patients with schizophrenia (n = 173) and control subjects (n = 236) were assessed for the DRD2 Ser311Cys variant. Schizophrenic patients displayed higher Cys311 allele frequencies than control subjects (4.