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Biomedical subjects

G Greenspan

Publications and source records attributed to G Greenspan.

16 recordsLinked to original sources
PubMed2005

Modeling haplotype block variation using Markov chains.

Models of background variation in genomic regions form the basis of linkage disequilibrium mapping methods. In this work we analyze a background model that groups SNPs into haplotype blocks and represents the dependencies between blocks by a Markov chain. We develop an error measure to compare the performance of this model against the common model that assumes that blocks are independent. By examining data from the International Haplotype Mapping project, we show how the Markov model over haplotype blocks is most accurate when representing blocks in strong linkage disequilibrium. This contrasts with the independent model, which is rendered less accurate by linkage disequilibrium. We provide a theoretical explanation for this surprising property of the Markov model and relate its behavior to allele diversity.

Chromosome Mapping↗
PubMed2004

High density linkage disequilibrium mapping using models of haplotype block variation.

MOTIVATION: The presence of millions of single nucleotide polymorphisms (SNPs) in the human genome has spurred interest in genetic mapping methods based on linkage disequilibrium. The recently discovered haplotype block structure of human variation promises to improve the effectiveness of these methods. A key difficulty for mapping techniques is the cost involved in separately identifying the haplotypes on each of an individual's chromosomes. RESULTS: We present a new approach for performing linkage disequilibrium mapping using high density haplotype or genotype data. Our method is based on a statistical model of haplotype block variation, which takes account of recombination hotspots, bottlenecks, genetic drift and mutation. We test our technique on two empirically determined high density datasets, attempting to recover the location of an SNP which was hidden and converted into phenotype information. We compare the results against a mapping method based on individual SNPs as well as a competing haplotype-based approach. We show that our strategy significantly outperforms these other approaches when used as a guide for resequencing and that it can also deal with both unphased genotype data and low penetrance diseases. AVAILABILITY: HaploBlock executables for Linux, Mac OS X and Sun OS, as well as user documentation, are available online at http://bioinfo.cs.technion.ac.il/haploblock/

Artificial Intelligence↗
PubMed2004

Model-based inference of recombination hotspots in a highly variable oncogene [corrected].

An emergent problem in the study of pathogen evolution is our ability to determine the extent to which their rapidly evolving genomes recombine. Such information is necessary and essential for locating pathogenicity loci using association studies, and it also directs future screening, therapeutic and vaccination strategies. Recombination also complicates the use of phylogenetic approaches to infer evolutionary parameters including selection pressures. Reliable methods that identify the presence of regions of recombination are therefore vital. We illustrate the use of an integrated model-based approach to inferring recombination structure using all available sequences of the highly variable, transforming Kaposi's sarcoma-associated herpesviral gene, ORF-K1. This technique learns the parameters of a statistical model that takes recombination hotspots, population genetic effects, and variable rates of mutation into account. As there are no known mechanisms to explain the high mutation rate in this DNA viral gene, recombination may account for some of the variability observed. We infer recombination hotspots in conserved sites such as the tyrosine kinase signaling motif, referred to here as recombination drift, as well as in nonconserved sites, a process described as recombination shift.

Bayes Theorem↗
PubMed1988

Clinical efficacy of intravenous morphine administration in hepatobiliary imaging for acute cholecystitis.

The most urgent diagnosis addressed by cholescintigraphy is acute cholecystitis. By administering low-dose intravenous morphine sulfate to patients undergoing cholescintigraphy (who demonstrate visualization of both the common bile duct and intestine and nonvisualization of the gallbladder), the time required to complete the study has been reduced to a maximum of 90 minutes. One hundred twenty-eight patients underwent cholescintigraphy for clinically suspected acute cholecystitis. Forty patients received intravenous morphine sulfate during the procedure. In patients who received morphine sulfate during the examination, the sensitivity of cholescintigraphy for the diagnosis of acute cholecystitis was 100%; the specificity was 85%.

Acute Disease↗
PubMed1987

Radiolabeled sucralfate: a review of clinical efficacy.

Radiolabeled sucralfate has been utilized by several investigators to evaluate peptic ulcer, active inflammatory bowel disease, esophageal ulcer, and gastric cancer. A review of the available literature indicates that radiolabeled sucralfate has been used to evaluate peptic ulcer and active inflammatory bowel diseases with high sensitivity and specificity. Other possible uses of radiolabeled sucralfate which have been less thoroughly studied and for which data are inadequate to accurately determine sensitivity and specificity include the detection of gastric cancer and esophageal ulceration.

Colitis↗
PubMed1982

Abnormal 99mTc-PIPIDA scans mistaken for common duct obstruction.

99mTc-PIPIDA scans were obtained in three patients with acute abdominal pain. The appearance of the scans suggested partial common duct obstruction. Two patients underwent surgery. One had acute appendicitis and the second had infarction of the distal ileum. In both cases, the gallbladder and biliary tract were normal. The third patient had been treated with morphine, which is known to increase biliary tract pressure and may cause contraction of the sphincter of Oddi. An ultrasound study of the gallbladder was normal and all symptoms resolved within 24 hours. Subsequently, three additional patients without biliary disease have been seen who had similar hepatobiliary scans. All three had received meperidine prior to the study. It is concluded that acute abdominal disease or the administration of morphine sulfate or meperidine can result in a scan pattern suggesting partial distal common duct obstruction in the absence of gallbladder or biliary tract disease.

Abdomen, Acute↗