Linkage studies in schizophrenia have identified a candidate region on chromosome 10p14–11 as reported for several independent samples. We investigated association of DNA sequence variants in a plausible candidate gene located in this region, the gene for phosphatidylinositol-4-phosphate 5-kinase II α (PIP5K2A), in a sample of 65 sib-pair families for which linkage had been reported. Evidence for association was obtained for 15 polymorphisms spanning 73.6 kb in the genomic region of the gene between intron 4 and the 3′ untranslated region, a region with high degree of linkage disequilibrium. Single nucleotide polymorphism (SNP) rs10828317 located in exon 7 and causing a non-synonymous amino-acid exchange (asparagine/serine) produced a P -value of 0.001 (experiment-wide significance level 0.00275) for over-transmission of the major allele coding for serine, analysed by transmission disequilibrium test using FAMHAP. Association of this SNP with schizophrenia has been also described in a sample of 273 Dutch schizophrenic patients and 580 controls ( P =0.0004). PIP5K2A is involved in the biosynthesis of phosphatidylinositol-4,5-bisphosphate (PI(4,5)P 2 ), one of the key metabolic crossroads in phosphoinositide signalling. PI(4,5)P 2 plays a role in membrane transduction of neurotransmitter signals as well as in intracellular signalling, pathways that may be impaired in schizophrenia.

Endometrial stromal sarcomas (ESS) are very rare neoplasms constituting less than 0.5% of all malignant uterine tumors. The aim of the present study was to characterize the karyotypic abnormalities in these malignant mesenchymal tumors and to find specific chromosomal aberrations with eventual correlation with histologic grades.Twelve cases of endometrial stromal sarcomas consisting of nine low-grade ESS and three undifferentiated endometrial sarcomas (UES) were investigated by comparative genomic hybridization (CGH).Ten of the twelve cases (83.3%) displayed chromosomal gains or losses. Deletions occurred more frequently than gains (63.4% versus 36.6%). In low-grade ESS, gains on 1, 6q, 9q, 16p, 19, 20q, 22q and losses on 2, 4q, 6, 7, 11q, 13q, 15q, 16q, 20p, X were detected. CGH with UES exhibited gains on 2q, 4q, 6q, 7p, 9q, 20q and losses on 3q, 10p, 14q. One low-grade ESS and one UES did not reveal any chromosomal aberration.Chromosomal aberrations in endometrial sarcomas are heterogeneous and do not clearly correlate with the histologic grades. There is no increased accumulation of aberrations from low-grade ESS to UES. Despite the karyotypic variations, chromosomal deletion on 7p was the most common finding (55.6%) in low-grade ESS and may play a role in tumor development and progression.

Evidence from epidemiological studies and segregation analysis suggests oligo- or polygenic inheritance in schizophrenia. Since model independent methods are thought to be most appropriate for linkage analysis in complex disorders, we performed a genome-wide autosomal screen in 71 families from Germany and Israel containing 86 independent affected sib-pairs with parental genotype information for statistical analysis strictly identity by descent. We genotyped 305 individuals with 463 markers at an average distance of approximately 10 cM genome-wide, and 1–2 cM in candidate regions (5q, 6p, q, 8p, 10p, 18p, 22q). The highest multipoint LOD scores (ASPEX) were obtained on 6p (D6S260, LOD = 2.0; D6S274, LOD = 2.2, MHC region, LOD = 2.15) and on 10p (D10S1714, LOD = 2.1), followed by 5q (D5S2066, LOD = 1.36), 6q (D6S271, LOD = 1.12; D6S1613, LOD = 1.11), 1q (D1S2675, LOD = 1.04), and 18p (broad disease model: D18S1116, LOD = 1.0). One hundred and thirty-three additional family members were available for some of the families (extended families) and were genotyped for these regions. GENEHUNTER produced a maximum NPL of 3.3 ( P = 0.001) for the MHC region and NPL of 3.13 ( P = 0.0015) for the region on 10p. There is support for these regions by independent groups. In genome-wide TDT analysis (sTDT, implemented in ASPEX), no marker passed the significance level of 0.0001 given by multiple testing, but nominal significance values for D10S211 ( P = 0.03) and for GOLF ( P = 0.0032) support further the linkage results on 10p and 18p. Our survey of 22 chromosomes identified candidate regions which should be useful to screen for schizophrenia susceptibility genes.

Temporal perception abilities refer to timing mechanisms used in daily life, such as the ability to reproduce and judge time, previously associated with the basal ganglia and the cerebellum, respectively. In individuals affected by velo-cardio-facial (VCFS), both the basal ganglia and the cerebellum have been shown to be particularly vulnerable to abnormal brain development, though related temporal perception abilities have yet to be investigated. In this study, our goal was to characterize time perception and reproduction abilities in individuals with VCFS. Compared to controls, we hypothesized that individuals with VCFS would be less accurate and show more variability when reproducing a fixed-interval series of auditory beeps; furthermore, we predicted that they would show a higher perceptive acuity threshold when discriminating between subtle time differences.Forty-two subjects with VCFS and 35 matched controls participated in temporal perception evaluations. In the reproduction of time finger-tapping task, subjects were asked to press a button in cadence with a series of fixed interval beeps, and then to hold the same tempo when the beeps stopped. Overall, the VCFS group showed less accuracy and more variability in reproduction ability when compared to controls. In the second experiment, subjects were tested on auditory and visual time perception tasks. Subjects were presented with a fixed interval stimulus and a stimulus of varying duration, and were asked to determine the longer of the two. The VCFS group required a greater discrepancy between tones to accurately discriminate the two stimuli. The results point to an alteration in temporal perception associated with VCFS. Implications of altered temporal perception abilities and their relationship to the VCFS phenotype are discussed.

Suggestive evidence for a potential susceptibility locus for schizophrenia at 5q31 was obtained in two family samples. Sample I consisted of 14 families with schizophrenia and revealed for the marker IL9 a lod score of 1.8 by two point lod score analysis. Sample II comprised 44 families including four from sample I and was ascertained in order to employ affected sib-pair analysis by identity by descent. A lod score of 1.8 around the marker D5S399 was obtained by multipoint analysis. The lod score remained positive, but decreased to 1.27 when the four families from sample I were excluded in order to use sample II as a statistically independent replication sample. We propose a susceptibility locus for schizophrenia with probably minor contribution in the pedigrees under investigation.

Für schizophrene Erkrankungen besteht ein deutlich erhöhtes genetisches Risiko, belegt durch Familien-, Zwillings- und Adoptionsstudien [1]. Die Konkordanzrate bei eineiigen Zwillingen beträgt etwa 50%, ein im Vergleich zu zweieiigen Zwillingen etwa 3fach erhöhtes Erkrankungsrisiko [1]. Ein einfacher Mendelscher Erbgang mit einem einzigen verantwortlichen Genort ist jedoch nicht nachweisbar. Schizophrene Erkrankungen gehören wie zum Beispiel auch Diabetes, Bluthochdruck, Krebserkrankungen, zu den komplexen genetischen Erkrankungen mit polygener, bzw. multifaktorieller Vererbung.