Leena Peltonen

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..Despite the obvious genetic and environmental complications, geneticists have targeted several population isolates for mapping genes for complex diseases...

..Further work will be required to characterize the interactiving molecules and metabolic pathways involved in the pathogenesis of NCLs...

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..Notably, this and other converging lines of evidence underline the importance of DISC1-related functional pathways in the etiology of schizophrenia...

..To conclude, the DAP12-TREM2 complex unlikely has a role in genetic susceptibility of MS...

..Our finding of mutated GLE1 exposes a common pathway connecting the genes implicated in LCCS1, LCCS2 and LCCS3 and elucidates mRNA processing as a critical molecular mechanism in motoneuron development and maturation...

..Bipolar disorder and schizophrenia are hypothesized to share some genetic background...

..There is an abundance of data from human genetic studies and animal models that implies a role for the disrupted in schizophrenia 1 gene (DISC1) in the etiology of schizophrenia and other major mental illnesses...

..The data underline the functional diversity of the molecules of the innate immune system and implies their significant contribution also in demyelinating CNS disorders, including those resulting in dementia...

..01 for C-G). These observations require replication, however, they suggest that the CNR1 gene may be a risk factor for ADHD and possibly PTSD, and that this gene warrants further investigation for a role in neuropsychiatric disorders...

..Possible explanations for this are that the genes might be relevant only to certain subtypes of the disease and/or only in certain populations...

..18). Thus the detailed genealogical information led us to identification of distinct linkage signals for schizophrenia susceptibility loci between the three analyses we performed...

..The established association of the same allelic variant of AKT1 with both cognitive and neuroanatomical aberrations could suggest that AKT1 exerts its effect on verbal learning and memory via neural networks involving prefrontal cortex...

..The loci on the centromeric region of 9p13 and the telomeric region of 7q31 may represent susceptibility loci for mood disorder in the Finnish population...

..1 region, we investigated a novel functional and positional candidate gene, helix/forkhead transcription factor (FOXC2), by sequencing and by genotyping of two single-nucleotide polymorphisms in the families...

..Finding of alternative associating haplotypes in the same set of BPD families gives evidence for allelic heterogeneity within DISC1, eventually leading to heterogeneity in the clinical outcome as well...

..We aimed to estimate whether the genetic risk profiles of coronary heart disease (CHD), ischemic stroke and the composite end-point of CVD differ between the genders...

..Chromosome 1q42 is among several genomic regions showing replicated evidence of linkage with schizophrenia, but the specific susceptibility mechanisms underlying this relationship remain to be identified...

..Because both DISC1 and NDE1 display association in our study sample, we hypothesized that other genes interacting with DISC1 might also have a role in the etiology of schizophrenia...

..Furthermore, these findings suggest that the putative role of low Persistence as an endophenotype for ADHD deserves further investigation...

..This study tests a series of allelic variants within such candidate genes to determine their potential influence on ADHD susceptibility...

..Both mouse-models replicate the NCL phenotype and neuropathology; the Cln1-/- model presents with early onset, severe neurodegenerative disease, whereas the Cln5-/- model produces a milder disease with a later onset...

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..These differences should be taken into account when considering normal values in these scales. The findings indicate that commonly used student samples are likely to be biased when compared to community based samples...

..In this study, we did not find association between the frequently studied ENPP1 K121Q variant, nor SNPs in the MCR or POMC genes and obesity or type 2 diabetes...

..These results suggest that variants in these four thrombosis genes contribute to arterial cardiovascular events at population level...

..Sex differences during fetal neurodevelopment should be investigated to fully elucidate the etiology of schizophrenia...

..This observation should stimulate further investigations of the role of this gene and protein in the pathogenesis of CVD...

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..Based on the association analysis results in a previously identified linkage region, we propose that HTR3C represents a novel candidate locus for ASDs and should be tested in other populations...

..Furthermore, results do not support a major role for NRG1, but we cannot completely exclude a minor role of this gene in the Finnish population...

..Further, the results provide interesting lessons concerning the impact of population history on the genome landscape of humans, as well as approaches to identify rare variants enriched in these subpopulations...

..No mutations were identified in the coding sequence...

..Humans have an innate preference for sweet taste, but the degree of liking for sweet foods varies individually...

..No detailed studies about the effect of APOA5 on atherosclerotic lesion formation have been conducted, nor has its potential interaction with USF1 been examined...

..The association observed between low-density lipoprotein and an infrequent variant in AR suggests the potential of such a cohort for identifying associations with both common, low-impact and rarer, high-impact quantitative trait loci...

..Our observations support a role for AIRE in peripheral tolerance and are the first ones to show that AIRE has a critical role in DC responses to microbial stimuli in humans...

..Our results reveal initial information on the effect of the loci associated with schizophrenia in multiple studies, and emphasize the value of trait components in the search for susceptibility loci for complex diseases...

..This study also demonstrates the potential of special isolated populations in search for variants contributing to complex traits...

..8 +/- 0.5 vs. 3.3 +/- 0.6, P < 0.01). This implies that acquired poor physical fitness is associated with defective expression of the oxidative pathway components in adipose tissue mitochondria...

..Thus it seems unlikely that DYX1C1 gene would be involved in the genetic etiology of autism in Finnish patients...

..014), and NLGN4 (DXS996, P=0.031). We conclude that neuroligin mutations most probably represent rare causes of autism and that it is unlikely that the allelic variants in these genes would be major risk factors for autism...

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..The fast release was also maintained after tableting. Loading of IMC into the Syloid particles alone was sufficient to produce similar IMC release profiles, as in the case of MCM-41 with the excipients...

..Importantly, apolipoprotein E (APOE) is the most downregulated gene in the risk individuals, linking the potential risk alleles of USF1 with the impaired APOE-dependent catabolism of atherogenic lipoprotein particles...

..These findings make the Ppt1Deltaex4 mouse an interesting model for the inflammation-associated death of interneurons...

..7. Since the identified chromosomal regions replicate earlier linkage findings in either bipolar disorder or other mental disorders, they should be considered good targets for further genetic analyses...

..Since the Cln5-/- mice do not exhibit significant brain atrophy, these mice could serve as models for studies on molecular processes associated with advanced aging...

..These results suggest that the MS predisposing locus on 5p is more complex than assumed and exemplify power of population isolates in the identification of rare disease alleles...

..These data demonstrate a nonlysosomal localization of sialin in neurons and would imply a role for sialin in the secretory processes of neuronal cells...

..The strongest evidence of association emerged from females. Our study supports the involvement of the dopamine pathway in temperament traits, in particular underlining the role of DRD2 in Novelty seeking, Harm avoidance and Persistence...

..Thus, we were not able to detect any statistically significant allelic associations. Re-sequencing based approaches may be required for elucidating the role chromosome 19q13 with MS...

..We tested this hypothesis with a genetic association analysis...

..The Drosophila melanogaster model confirmed these findings and provides evidence for the significance of the mutation both in vitro and in vivo...

..1 cM. Our results demonstrate the complexity of the concept of 'detectable LD' and emphasize the importance of understanding population history when designing a strategy for disease gene mapping...

..These findings provide a good starting point for the study of the molecular mechanisms of this inherited dementia and new evidence for the involvement of the immune system in neuronal degeneration...

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..7, consistent with earlier estimates. Our extension of the MFG test has general application to family-based studies of maternal-genotype and MFG interaction effects...

..The results from both populations suggest that about two thirds of variation in food neophobia is genetically determined...

..Typical of complex disease-associated genes, neither the explicit mutations have been described nor the functional consequences for risk allele carriers been reported at the cellular or tissue level...

..008) with marker D10S546. Suggestive evidence for linkage also emerged for HDL-C on 2q31 and for TGs on 20q13.32. Finnish families ascertained for dyslipidemias thus suggest that 10q11, 2q31, and 20q13.32 harbor loci for HDL-C and TGs...

..We did not observe significant linkage or association between any SNP and ASDs. Therefore, we suggest that common variants in GLO1 are not significant susceptibility factors for ASDs in the Finnish population...

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..003). The SLC6A14 gene is an interesting novel candidate for obesity because it encodes an amino acid transporter, which potentially regulates tryptophan availability for serotonin synthesis and thus possibly affects appetite control...

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..000011). Multipoint parametric (HLOD = 4.45; P=.0000058) and nonparametric (NPL(all) = 3.43; P=.0007) analyses support linkage in this region. Statistically significant linkage was not observed in any other chromosomal region...

..5 Mb. Thus, this study describes the restriction of an MS locus outside the HLA region into a segment approachable by molecular tools...

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..This is the first candidate-gene study to explicitly test for and provide evidence of a maternal-fetal genotype incompatibility mechanism in schizophrenia...

..A novel approach to finding candidate genes by using gene expression data through liquid association is developed and used to identify multiple sclerosis susceptibility candidate genes...

..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...

..We addressed here the role of NPS and NPSR1 as susceptibility genes for human anxiety disorders...

..In this study we targeted a 470 kb region on 2q11.2 presenting the locus with most evidence for linkage to severe OA of distal interphalangeal joints (DIP) in our genome wide scan families...

..Our approach demonstrates how genetic markers can be used to characterize the biology of prenatal risk factors of schizophrenia...

..The purpose of the study was to estimate the prevalence of attention-deficit/hyperactivity disorder (ADHD) and its clinical characteristics in the Northern Finland Birth Cohort 1986...

..To facilitate the genetic studies of stature we have also set up a website that lists all stature genome scans published and their most significant loci (http://www.genomeutwin.org/stature_gene_map.htm)...

..This is one of the first loci identified for apoB levels in humans and is the second major locus implicated in the genetic etiology of FCH...

..Our findings would also encourage more detailed analyses of the effect of DISC1 on the component-traits of schizophrenia...

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..11, the latter representing a recently characterized region for type 2 diabetes. Besides these three loci, loci on chromosomes 2p and 3p showed linkage in the families with low HDL-C and a locus on 2ptel in the families with FCHL...

..USF1 encodes a transcription factor known to regulate several genes of glucose and lipid metabolism...

..These data will facilitate the final cloning of the APECED gene and any other novel gene in this complex genomic region...

..We conclude that mutation of AIRE per se has little influence on the APECED phenotype, whereas, in contrast to earlier reports, HLA class II is a significant determinant...

..That the variant (C/T-13910) occurs in distantly related populations indicates that it is very old...

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..Conversely, ignoring genealogical makeup of the study population seems to disclose false negative and false positive associations, directing resources down the drain...

..Our results thereby do not support a major function of the tested MYO9B variants in MS...

..These data provide valuable information about the molecular pathways putatively active in motoneuron diseases...

..Linkage disequilibrium facilitated further restriction of the critical chromosomal region to approximately 80 kb, well within the limits of positional cloning techniques...

..The obtained long-range clones will form the basis for the isolation of a novel ataxia gene...

..Detailed analyses of these disease genes and their function have provided new insights into the structure and function of defective proteins as well as into the biology of affected tissues...

..These results lay the basis for the cloning of this novel dementia gene and for diagnostics in the Finnish population using haplotype analysis...

..Surprisingly, the LPH gene was shown to lie outside the critical CLD region, excluding it as a causative gene for CLD. The LPH locus was found to reside >2 Mb from the critical CLD region...

..Such precise information of the carrier frequencies could form the basis for targeted genetic screens in this population. Our approach describes a general paradigm for large-scale carrier-screening programs also in other populations...

..The results showed the power of linkage disequilibrium in the locus assignment of diseases with very limited family materials...

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..This replicates the previous linkage finding in the same region and constitutes supportive evidence for a susceptibility gene in this region...