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Beersheba, Israel

Baris H.N.,The Genetics Institute | Baris H.N.,Technion - Israel Institute of Technology | Weisz Hubshman M.,The Raphael Recanati Genetics Institute | Weisz Hubshman M.,Tel Aviv University | And 5 more authors.
Blood Cells, Molecules, and Diseases

Bone crises in type 1 Gaucher disease are reported in long bones and occasionally in weight bearing bones and other bones, but rarely in small bones of the hands and feet. We retrospectively examined the incidence of bone pain in patients followed at the Rabin Medical Center, Israel, before and following the initiation of enzyme replacement therapy (ERT) and evaluated them for bone crises. Of 100 type I Gaucher disease patients, 30 (30%) experienced one or more bone crises. Small bone crises represented 31.5% of all bone crises and were always preceded by crises in other bones. While the incidence of long bone crises reduced after the initiation of ERT, small bone crises increased. Almost 60% of patients with bone crises were of the N370S/84GG genotype suggesting a greater susceptibility of N370S/84GG patients to severe bone complications. These patients also underwent the greatest number of splenectomies (70.6% of splenectomised patients). Splenectomised patients showed a trend towards increased long and small bone crises after surgery. Active investigation of acute pain in the hands and feet in patients in our cohort has revealed a high incidence of small bone crises. Physicians should consider imaging studies to investigate unexplained pain in these areas. © 2015 Elsevier Inc. Source

Stelzer G.,Weizmann Institute of Science | Stelzer G.,LifeMap science Ltd. | Plaschkes I.,LifeMap science Ltd. | Oz-Levi D.,Weizmann Institute of Science | And 20 more authors.
BMC Genomics

Background: Next generation sequencing (NGS) provides a key technology for deciphering the genetic underpinnings of human diseases. Typical NGS analyses of a patient depict tens of thousands non-reference coding variants, but only one or very few are expected to be significant for the relevant disorder. In a filtering stage, one employs family segregation, rarity in the population, predicted protein impact and evolutionary conservation as a means for shortening the variation list. However, narrowing down further towards culprit disease genes usually entails laborious seeking of gene-phenotype relationships, consulting numerous separate databases. Thus, a major challenge is to transition from the few hundred shortlisted genes to the most viable disease-causing candidates. Results: We describe a novel tool, VarElect ( http://ve.genecards.org ), a comprehensive phenotype-dependent variant/gene prioritizer, based on the widely-used GeneCards, which helps rapidly identify causal mutations with extensive evidence. The GeneCards suite offers an effective and speedy alternative, whereby >120 gene-centric automatically-mined data sources are jointly available for the task. VarElect cashes on this wealth of information, as well as on GeneCards' powerful free-text Boolean search and scoring capabilities, proficiently matching variant-containing genes to submitted disease/symptom keywords. The tool also leverages the rich disease and pathway information of MalaCards, the human disease database, and PathCards, the unified pathway (SuperPaths) database, both within the GeneCards Suite. The VarElect algorithm infers direct as well as indirect links between genes and phenotypes, the latter benefitting from GeneCards' diverse gene-to-gene data links in GenesLikeMe. Finally, our tool offers an extensive gene-phenotype evidence portrayal ("MiniCards") and hyperlinks to the parent databases. Conclusions: We demonstrate that VarElect compares favorably with several often-used NGS phenotyping tools, thus providing a robust facility for ranking genes, pointing out their likelihood to be related to a patient's disease. VarElect's capacity to automatically process numerous NGS cases, either in stand-alone format or in VCF-analyzer mode (TGex and VarAnnot), is indispensable for emerging clinical projects that involve thousands of whole exome/genome NGS analyses. © 2016 Stelzer et al. Source

Sharony R.,The Genetics Institute | Sharony R.,Meir Medical Center | Sharony R.,Tel Aviv University | Kelz E.,Meir Medical Center | And 4 more authors.
Early Human Development

Background: Reports on the morphometric analysis of umbilical cord (UC) and its vessels have been inconsistent due to varying inclusion criteria and methodology. The current study tried to overcome the limitations of previous studies by comparing the UC in pregnancies complicated by fetal growth restriction (FGR), preeclampsia (PE) and FGR. +. PE, to healthy controls. Aims: Analyze the morphometric attributes of the UC in pregnancies complicated by FGR and PE. Study design: Case-control. Subjects: The study groups consisted of 36 patients with FGR. +. PE, 72 with FGR (without PE) and 15 with PE (without FGR). They were compared to 50 patients without FGR or PE. Outcome measures: Histological cross-sections of the UC were photographed and measured. The following variables were recorded: cross-section area of UC, thickness and surface area of umbilical vessel walls, shortest distance between cord surface and nearest artery (DSA), distance between the arteries (DBA) and placental weight and measurements. The area of the Wharton's jelly (WJ) area was calculated. Results: UC and WJ cross-section areas were significantly smaller in FGR + PE and FGR, but not in PE. The umbilical vessel wall area was decreased in FGR + PE, but the thickness was not significantly decreased in all three study groups, compared to controls. DSA was smaller in all three groups, whereas DBA was not significantly different, compared to controls. Conclusions: Smaller UC cross-section areas were seen in FGR and FGR + PE, but not in PE without FGR. However, there is no evidence to determine whether this reduction is a cause or consequence of FGR. Reduced DSA in PE, whose UC cross-section area was not smaller as in FGR and FGR + PE, might reflect alterations in UC induced by PE. © 2015 Elsevier Ireland Ltd. Source

Markus B.,Ben - Gurion University of the Negev | Birk O.S.,Ben - Gurion University of the Negev | Birk O.S.,The Genetics Institute | Geiger D.,Technion - Israel Institute of Technology

Motivation: High-throughput single nucleotide polymorphism (SNP) arrays have become the standard platform for linkage and association analyses. The high SNP density of these platforms allows high-resolution identification of ancestral recombination events even for distant relatives many generations apart. However, such inference is sensitive to marker mistyping and current error detection methods rely on the genotyping of additional close relatives. Genotyping algorithms provide a confidence score for each marker call that is currently not integrated in existing methods. There is a need for a model that incorporates this prior information within the standard identical by descent (IBD) and association analyses. Results: We propose a novel model that incorporates marker confidence scores within IBD methods based on the Lander-Green Hidden Markov Model. The novel parameter of this model is the joint distribution of confidence scores and error status per array. We estimate this probability distribution by applying a modified expectation-maximization (EM) procedure on data from nuclear families genotyped with Affymetrix 250K SNP arrays. The converged tables from two different genotyping algorithms are shown for a wide range of error rates. We demonstrate the efficacy of our method in refining the detection of IBD signals using nuclear pedigrees and distant relatives. © The Author 2011. Published by Oxford University Press. All rights reserved. Source

Shalev S.A.,The Genetics Institute

The principle deeds of genetics in Israel consist of a wide array of disciplines including agriculture, nutrients, biotechnology, pharmacology and pharmacogenetics, pertaining to criminal as well as medical aspects. In the scope of this state of the art historical review, the authors emphasize the medical issues. The initial stimulus for genetic studies and medical awareness among the various ethnic populations in Israel was the immigration, in the early 1950s, of over a million Jewish immigrants from more than 100 countries from all continents. It was soon recognized that frequencies of genetic diseases differed markedly among the various communities, serving as a trigger for studying and managing these populations. In this state of the art historical review, particular emphasize was given to the historical events concerning genetics in the land of Israel, as well as in the state of Israel. Highlights of genetic diversity of the various ethnic and sub-populations are added, along with the advances and major achievements of the human genetics discipline in the state of Israel. Source

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