Tombstones; Hochberg Jewish Cemetery Cemeteries; Tombs

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Tombstones; Hochberg Jewish Cemetery Cemeteries; Tombs

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Tomb of Salomon Pappenheimer; Hochberg Jewish Cemetery Cemeteries; Tombs

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Tomb next to tomb of Salomon Pappenheimer; Hochberg Jewish Cemetery Cemeteries; Tombs

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Tomb next to tomb of Salomon Pappenheimer; Hochberg Jewish Cemetery Cemeteries; Tombs

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Tombstones; Hochberg Jewish Cemetery Cemeteries; Tombs

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Tomb of Nehemias Dreifus; Hochberg Jewish Cemetery Cemeteries; Tombs

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Tombstone; Hochberg Jewish Cemetery Cemeteries; Tombs

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Tomb of Gutele Wormser; Hochberg Jewish Cemetery Cemeteries; Tombs

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Tomb of Salomon Pappenheimer; Hochberg Jewish Cemetery Cemeteries; Tombs

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Integrating sorghum whole genome sequence information with a compendium of sorghum QTL studies reveals uneven distribution of QTL and of gene-rich regions with significant implications for crop improvement.

A comprehensive analysis was conducted using 48 sorghum QTL studies published from 1995 to 2010 to make information from historical sorghum QTL experiments available in a form that could be more readily used by sorghum researchers and plant breeders. In total, 771 QTL relating to 161 unique traits from 44 studies were projected onto a sorghum consensus map. Confidence intervals (CI) of QTL were estimated so that valid comparisons could be made between studies. The method accounted for the number of lines used and the phenotypic variation explained by individual QTL from each study. In addition, estimated centimorgan (cM) locations were calculated for the predicted sorghum gene models identified in Phytozome (JGI GeneModels SBI v1.4) and compared with QTL distribution genome-wide, both on genetic linkage (cM) and physical (base-pair/bp) map scales. QTL and genes were distributed unevenly across the genome. Heterochromatic enrichment for QTL was observed, with approximately 22% of QTL either entirely or partially located in the heterochromatic regions. Heterochromatic gene enrichment was also observed based on their predicted cM locations on the sorghum consensus map, due to suppressed recombination in heterochromatic regions, in contrast to the euchromatic gene enrichment observed on the physical, sequence-based map. The finding of high gene density in recombination-poor regions, coupled with the association with increased QTL density, has implications for the development of more efficient breeding systems in sorghum to better exploit heterosis. The projected QTL information described, combined with the physical locations of sorghum sequence-based markers and predicted gene models, provides sorghum researchers with a useful resource for more detailed analysis of traits and development of efficient marker-assisted breeding strategies.

Genetic studies on recurrent miscarriage

Recurrent miscarriage (RM) is defined as three consecutive pregnancy failures and is estimated to affect ~1% of couples trying to conceive. The cause of RM remains unknown in approximately 50% of cases. In this study, it was hypothesized that some of the underlying factors yet to be discovered are genetic. The aim was to search for mutations in genes AMN, EPCR, TM, and p53 known to cause miscarriage in mouse models and thereby find new genetic causes for unexplained miscarriages in humans. In addition, the mitochondrial genome was studied because mitochondria are involved in processes important in early development. Furthermore, sex chromosome characteristics suggested to underlie miscarriage were also studied. A total of 40 couples and 8 women with unexplained RM were collected for this study and screened for mutations in the candidate genes. Six interesting exonic or potential splice site disrupting variations were detected. However, their phenotypic effects cannot be determined without further investigations. Additionally, an association between the C11992A polymorphism of the p53 gene and RM was detected. The results indicate that women carrying the C/A or A/A genotype have a two-fold higher risk for RM than women with a C/C genotype. This strengthens the results of previous studies reporting that p53 sequence variations may cause miscarriage. The role of variation C11992A in embryonic development is, however, difficult to predict without further studies When screening the mitochondrial genome a heteroplasmic mtDNA variation was found in an unexpected high number of women, as heteroplasmic variations are reported to be rare. One novel variation and 18 previously reported polymorphisms were detected in the mitochondrial genome. Although the detected variations are likely to be neutral polymorphisms, a role in the aetiology of miscarriage cannot be excluded as some mtDNA variations may be pathogenic only when a threshold is reached. Recent publications have reported skewed X chromosome inactivation and Y chromosome microdeletions to be associated with RM. Therefore, these sex chromosome abnormalities in the context of RM were investigated. No associations between skewed X chromosome inactivation or Y chromosome microdeletions and RM in the Finnish patients were detected. Data on ancestral birthplaces of the patients were collected to study any possible geographic clustering, which would indicate a common predisposing factor. The results showed clustering of the birthplaces in eastern Finland in a subset of patients. This suggests a possibility of an enriched susceptibility gene which may contribute to RM.

"Klo-Ku-Ba", Hans and Elizabeth Krakauer's first apartment in the basement of the Jewish Hospital; Hannover, Germany.

"Klo-Ku-Ba" the first apartment of Hans and Elizabeth in the basement of the Jewish Hospital in Hannover, Germany. The one room served as kitchen, bedroom, and bathroom which was shared by the other residents on the medical staff. Klo-Ku-Ba: Klosett, Kueche, Bad

Studies of the genetic epidemiology of cardiovascular disease: focus on inflammatory candidate genes

Cardiovascular disease (CVD) is a complex disease with multifactorial aetiology. Both genetic and environmental factors contribute to the disease risk. The lifetime risk for CVD differs markedly between men and women, men being at increased risk. Inflammatory reaction contributes to the development of the disease by promoting atherosclerosis in artery walls. In the first part of this thesis, we identified several inflammatory related CVD risk factors associating with the amount of DNA from whole blood samples, indicating a potential source of bias if a genetic study selects the participants based on the available amount of DNA. In the following studies, this observation was taken into account by applying whole genome amplification to samples otherwise subjected to exclusion due to very low DNA yield. We continued by investigating the contribution of inflammatory genes to the risk for CVD separately in men and women, and looked for sex-genotype interaction. In the second part, we explored a new candidate gene and its role in the risk for CVD. Selenoprotein S (SEPS1) is a membrane protein residing in the endoplasmic reticulum where it participates in retro-translocation of unfolded proteins to cytosolic protein degradation. Previous studies have indicated that SEPS1 protects cells from oxidative stress and that variations in the gene are associated with circulating levels of inflammatory cytokines. In our study, we identified two variants in the SEPS1 gene, which associated with coronary heart disease and ischemic stroke in women. This is, to our knowledge, the first study suggesting a role of SEPS1 in the risk for CVD after extensively examining the variation within the gene region. In the third part of this thesis, we focused on a set of seven genes (angiotensin converting enzyme, angiotensin II receptor type I, C-reactive protein (CRP), and fibrinogen alpha-, beta-, and gamma-chains (FGA, FGB, FGG)) related to inflammatory cytokine interleukin 6 (IL6) and their association with the risk for CVD. We identified one variant in the IL6 gene conferring risk for CVD in men and a variant pair from IL6 and FGA genes associated with decreased risk. Moreover, we identified and confirmed an association between a rare variant in the CRP gene and lower CRP levels, and found two variants in the FGA and FGG genes associating with fibrinogen. The results from this third study suggest a role for the interleukin 6 pathway genes in the pathogenesis of CVD and warrant further studies in other populations. In addition to the IL6 -related genes, we describe in this thesis several sex-specific associations in other genes included in this study. The majority of the findings were evident only in women encouraging other studies of cardiovascular disease to include and analyse women separately from men.

Studies on immune activation in rheumatoid arthritis and reactive arthritis

Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovitis, progressive joint destruction, and disability. Reactive arthritis (ReA) is a sterile joint inflammation following a distant mucosal infection. The clinical course of these diseases is variable and cannot be predicted with reasonable accuracy by clinical and laboratory markers. The predictive value of circulating soluble interleukin-2 receptor (sIL-2R), a marker of lymphocyte activation, measured by Immulite® automated immunoassay analyzer, was evaluated in two cohorts of RA patients. In 175 patients with active early RA randomized to treatment with either on disease-modifying antirheumatic drug (DMARD) or a combination of 3 DMARDs and prednisolone, low baseline sIL-2R level predicted remission after 6 months in patients treated with a single DMARD. In 24 patients with active RA refractory to DMARDs, low baseline sIL-2R level predicted rapid clinical response to treatment with infliximab, an anti-tumour necrosis factor antibody. Furthermore, in a cohort of 26 patients with acute ReA, high baseline sIL-2R level predicted remission after 6 months. Levels of circulating soluble E-selectin (sE-selectin), a marker of endothelial activation, were measured annually by enzyme-linked immunosorbent assay (ELISA) in a cohort of 85 patients with early RA. During a five-year follow-up, sE-selectin levels were associated with activity and outcome of RA. The levels of neutrophil and monocyte CD11b/CD18 expression measured by flow cytometry, and circulating levels of sE-selectin measured by ELISA, and procalcitonin by immunoluminometric assay, were compared in 28 patients with acute ReA and 16 patients with early RA. The levels of the markers were comparable in ReA, RA, and healthy control subjects. In conlusion, sIL-2R may provide a new predictive marker in early RA treated with a single DMARD and refractory RA treated with infliximab. In addition, sIL-2R level predicts remission in acute ReA.