Annotated Chromosome Maps for Renal Disease

A combination of linkage analyses and association studies are currently employed to promote the identification of genetic factors contributing to inherited renal disease. We have standardized and merged complex genetic data from disparate sources, creating unique chromosomal maps to enhance genetic epidemiological investigations. This database and novel renal maps effectively summarize genomic regions of suggested linkage, association, or chromosomal abnormalities implicated in renal disease. Chromosomal regions associated with potential intermediate clinical phenotypes have been integrated, adding support for particular genomic intervals. More than 500 reports from medical databases, published scientific literature, and the World Wide Web were interrogated for relevant renal-related information. Chromosomal regions highlighted for prioritized investigation of renal complications include 3q13-26, 6q22-27, 10p11-15, 16p11-13, and 18q22. Combined genetic and physical maps are effective tools to organize genetic data for complex diseases. These renal chromosome maps provide insights into renal phenotype-genotype relationships and act as a template for future genetic investigations into complex renal diseases. New data from individual researchers and/or future publications can be readily incorporated to this resource via a user-friendly web-form accessed from the website: www.qub.ac.uk/neph-res/CORGI/index.php.

Chromosome 9p21.3 is associated with early-onset coronary heart disease in the Irish population

Coronary heart disease (CHD) remains a leading cause of death across the world. A region on chromosome 9p21.3 has been recently reported to be associated with CHD. We evaluated 3 SNPs and 3 common haplotypes in the 9p21.3 region in 1494 individuals from 580 Irish families, where at least 1 member had early-onset (males

Association Analysis of the PIP4K2A Gene on Chromosome 10p12 and Schizophrenia in the Irish Study of High Density Schizophrenia Families (ISHDSF) and the Irish Case-Control Study of Schizophrenia (ICCSS)

Molecular studies support pharmacological evidence that phosphoinositide signaling is perturbed in schizophrenia and bipolar disorder. The phosphatidylinositol-4-phosphate-5-kinase type-II alpha (PIP4K2A) gene is located on chromosome 10p12. This region has been implicated in both diseases by linkage, and PIP4K2A directly by association. Given linkage evidence in the Irish Study of High Density Schizophrenia Families (ISHDSF) to a region including 10p12, we performed an association study between genetic variants at PIP4K2A and disease. No association was detected through single-marker or haplotype analysis of the whole sample. However, stratification into families positive and negative for the ISHDSF schizophrenia high-risk haplotype (HRH) in the DTNBP1 gene and re-analysis for linkage showed reduced amplitude of the 10p12 linkage peak in the DTNBP1 HRH positive families. Association analysis of the stratified sample showed a trend toward association of PIP4K2A SNPs rs1417374 and rs1409395 with schizophrenia in the DTNBP1 HRH positive families. Despite this apparent paradox, our data may therefore suggest involvement of PIP4K2A in schizophrenia in those families for whom genetic variation in DTNBP1 appears also to be a risk factor. This trend appears to arise from under-transmission of common alleles to female cases. Follow-up association analysis in a large Irish schizophrenia case-control control sample (ICCSS) showed significant association with disease of a haplotype comprising these same SNPs rs1417374-rs1409395, again more so in affected females, and in cases with negative family history of the disease. This study supports a minor role for PIP4K2A in schizophrenia etiology in the Irish population. (C) 2009 Wiley-Liss, Inc.

Novel linkage to chromosome 20p using latent classes of psychotic illness in 270 Irish high-density families

Background: Several lines of evidence suggest that the clinical heterogeneity of schizophrenia is due to genetic heterogeneity. Genetic heterogeneity may decrease the signal-to-noise ratio in linkage and association studies. Therefore, linkage studies of clinically homogeneous classes of psychotic illness may result in greater power to detect at least some loci.

UNUSUAL CHROMOSOME-NUMBER OF GRACILARIA-VERRUCOSA (GRACILARIALES, RHODOPHYTA) IN THE CAPE-GRIS-NEZ AREA, NORTHERN FRANCE

The chromosome number of Gracilaria verrucosa (Hudson) Papenfuss was estimated in numerous individuals from different populations of the Cape Gris-Nez area of Northern France. To optimize estimates and to minimize counting errors, several counts were made on the same nucleus and in different nuclei of the same individual. The haploid chromosome number was estimated in vegetative gametophytic cells and tetrasporocytic cells; the diploid number was estimated from tetrasporophytic vegetative cells. The basic haploid number was n = 17 +/- 1, whereas all other Gracilaria species for which chromosome numbers are available are reported to have n = 24. These include populations of G. verrucosa from Norway and Wales that have previously been shown to be conspecific with the Cape Gris-Nez populations by comparison of plastid DNA data. G. verrucosa is therefore one of the few red algae for which populations with different chromosome numbers are known.

SNP in the genome-wide association study hotspot on chromosome 9p21 confers susceptibility to diabetic nephropathy in type 1 diabetes

AIMS/HYPOTHESIS: Parental type 2 diabetes mellitus increases the risk of diabetic nephropathy in offspring with type 1 diabetes mellitus. Several single nucleotide polymorphisms (SNPs) that predispose to type 2 diabetes mellitus have recently been identified. It is, however, not known whether such SNPs also confer susceptibility to diabetic nephropathy in patients with type 1 diabetes mellitus. METHODS: We genotyped nine SNPs associated with type 2 diabetes mellitus in genome-wide association studies in the Finnish population, and tested for their association with diabetic nephropathy as well as with severe retinopathy and cardiovascular disease in 2,963 patients with type 1 diabetes mellitus. Replication of significant SNPs was sought in 2,980 patients from three other cohorts. RESULTS: In the discovery cohort, rs10811661 near gene CDKN2A/B was associated with diabetic nephropathy. The association remained after robust Bonferroni correction for the total number of tests performed in this study (OR 1.33 [95% CI 1.14, 1.56], p?=?0.00045, p (36tests)?=?0.016). In the meta-analysis, the combined result for diabetic nephropathy was significant, with a fixed effects p value of 0.011 (OR 1.15 [95% CI 1.02, 1.29]). The association was particularly strong when patients with end-stage renal disease were compared with controls (OR 1.35 [95% CI 1.13, 1.60], p?=?0.00038). The same SNP was also associated with severe retinopathy (OR 1.37 [95% CI 1.10, 1.69] p?=?0.0040), but the association did not remain after Bonferroni correction (p (36tests)?=?0.14). None of the other selected SNPs was associated with nephropathy, severe retinopathy or cardiovascular disease. CONCLUSIONS/INTERPRETATION: A SNP predisposing to type 2 diabetes mellitus, rs10811661 near CDKN2A/B, is associated with diabetic nephropathy in patients with type 1 diabetes mellitus.

Molecular cloning, expression, and regulation in Escherichia coli K-12 of a chromosome-mediated aerobactin iron transport system from a human invasive isolate of E. coli K1

We have cloned chromosomal genes determining the aerobactin iron transport system from the Escherichia coli K1 strain VW187. Mapping and hybridization experiments showed that the VW187 aerobactin region was identical to that of the plasmid ColV-K30. However, in the E. coli K-12 background, the biosynthesis of both siderophore and ferric aerobactin receptor encoded by the VW187-derived recombinant plasmids was not repressed by iron to the same extent found when a recombinant plasmid derived from pColV-K30 was used. RNA-DNA dot-blot hybridization experiments demonstrated that the aerobactin-specific mRNA synthesized by the VW187-derived clones was not iron regulated in E. coli K-12. In contrast, the synthesis of aerobactin and its receptor in strain VW187 was completely repressed by iron regardless of whether the recombinant plasmids originated from VW187 or pColV-K30. Similar results were obtained with gene fusions in which a promoterless lac operon was placed under the control of aerobactin promoter regions of either chromosome- or plasmid-mediated aerobactin systems. DNA sequencing of the chromosomal aerobactin promoter region showed changes in bases located immediately upstream to the -35 region compared with the corresponding region in pColV-K30, which is known to be part of the binding site for the Fur repressor protein.