Literature DB >> 23162081

A system for exact and approximate genetic linkage analysis of SNP data in large pedigrees.

Mark Silberstein1, Omer Weissbrod, Lars Otten, Anna Tzemach, Andrei Anisenia, Oren Shtark, Dvir Tuberg, Eddie Galfrin, Irena Gannon, Adel Shalata, Zvi U Borochowitz, Rina Dechter, Elizabeth Thompson, Dan Geiger.   

Abstract

MOTIVATION: The use of dense single nucleotide polymorphism (SNP) data in genetic linkage analysis of large pedigrees is impeded by significant technical, methodological and computational challenges. Here we describe Superlink-Online SNP, a new powerful online system that streamlines the linkage analysis of SNP data. It features a fully integrated flexible processing workflow comprising both well-known and novel data analysis tools, including SNP clustering, erroneous data filtering, exact and approximate LOD calculations and maximum-likelihood haplotyping. The system draws its power from thousands of CPUs, performing data analysis tasks orders of magnitude faster than a single computer. By providing an intuitive interface to sophisticated state-of-the-art analysis tools coupled with high computing capacity, Superlink-Online SNP helps geneticists unleash the potential of SNP data for detecting disease genes.
RESULTS: Computations performed by Superlink-Online SNP are automatically parallelized using novel paradigms, and executed on unlimited number of private or public CPUs. One novel service is large-scale approximate Markov Chain-Monte Carlo (MCMC) analysis. The accuracy of the results is reliably estimated by running the same computation on multiple CPUs and evaluating the Gelman-Rubin Score to set aside unreliable results. Another service within the workflow is a novel parallelized exact algorithm for inferring maximum-likelihood haplotyping. The reported system enables genetic analyses that were previously infeasible. We demonstrate the system capabilities through a study of a large complex pedigree affected with metabolic syndrome. AVAILABILITY: Superlink-Online SNP is freely available for researchers at http://cbl-hap.cs.technion.ac.il/superlink-snp. The system source code can also be downloaded from the system website. CONTACT: omerw@cs.technion.ac.il SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

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Year:  2012        PMID: 23162081      PMCID: PMC3546794          DOI: 10.1093/bioinformatics/bts658

Source DB:  PubMed          Journal:  Bioinformatics        ISSN: 1367-4803            Impact factor:   6.937


  53 in total

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Authors:  T D Dyer; J Blangero; J T Williams; H H Göring; M C Mahaney
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Review 2.  Linkage analysis in the next-generation sequencing era.

Authors:  Joan E Bailey-Wilson; Alexander F Wilson
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3.  Next-generation linkage analysis.

Authors:  Veronica J Vieland; Marcella Devoto
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Review 4.  Breaking loops in large complex pedigrees.

Authors:  Tatiana I Axenovich; Irina V Zorkoltseva; Fan Liu; Anatoly V Kirichenko; Yurii S Aulchenko
Journal:  Hum Hered       Date:  2007-09-26       Impact factor: 0.444

5.  Linkage analysis with dense SNP maps in isolated populations.

Authors:  Céline Bellenguez; Carole Ober; Catherine Bourgain
Journal:  Hum Hered       Date:  2009-04-09       Impact factor: 0.444

6.  Markov chain Monte Carlo segregation and linkage analysis for oligogenic models.

Authors:  S C Heath
Journal:  Am J Hum Genet       Date:  1997-09       Impact factor: 11.025

7.  Parametric and nonparametric linkage analysis: a unified multipoint approach.

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Journal:  Am J Hum Genet       Date:  1996-06       Impact factor: 11.025

Review 8.  Metabolic syndrome--a new world-wide definition. A Consensus Statement from the International Diabetes Federation.

Authors:  K G M M Alberti; P Zimmet; J Shaw
Journal:  Diabet Med       Date:  2006-05       Impact factor: 4.359

9.  A general model for the genetic analysis of pedigree data.

Authors:  R C Elston; J Stewart
Journal:  Hum Hered       Date:  1971       Impact factor: 0.444

10.  A multiple splitting approach to linkage analysis in large pedigrees identifies a linkage to asthma on chromosome 12.

Authors:  Céline Bellenguez; Carole Ober; Catherine Bourgain
Journal:  Genet Epidemiol       Date:  2009-04       Impact factor: 2.135

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  21 in total

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6.  MPZL2 is a novel gene associated with autosomal recessive nonsyndromic moderate hearing loss.

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7.  Hypomorphic caspase activation and recruitment domain 11 (CARD11) mutations associated with diverse immunologic phenotypes with or without atopic disease.

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Journal:  J Allergy Clin Immunol       Date:  2018-08-28       Impact factor: 10.793

8.  Sonic Hedgehog Intron Variant Associated With an Unusual Pediatric Cortical Cataract.

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9.  Allelic Mutations of KITLG, Encoding KIT Ligand, Cause Asymmetric and Unilateral Hearing Loss and Waardenburg Syndrome Type 2.

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Journal:  Am J Hum Genet       Date:  2015-10-29       Impact factor: 11.025

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