Association mapping using pooled DNA.

The genetic dissection of complex disorders via genetic marker data has gained popularity in the postgenome era. Methods for typing genetic markers on human chromosomes continue to improve. Compared with the popular individual genotyping experiment, a pooled-DNA experiment (alleotyping experiment) is more cost effective when carrying out genetic typing. This chapter provides an overview of association mapping using pooled DNA and describes a five-stage study design including the preliminary calibration of peak intensities, estimation of allele frequency, single-locus association mapping, multilocus association mapping, and a confirmation study. Software and an analysis of authentic data are presented. The strengths and weaknesses of pooled-DNA analyses, as well as possible future applications for this method, are discussed.

[1]  M. Soller,et al.  Selective DNA pooling for determination of linkage between a molecular marker and a quantitative trait locus. , 1994, Genetics.

[2]  Robert C Elston,et al.  Estimating haplotype frequencies in pooled DNA samples when there is genotyping error , 2004, BMC Genetics.

[3]  Jing Huang,et al.  Algorithms for large-scale genotyping microarrays , 2003, Bioinform..

[4]  C. Halldén,et al.  Estimating genetic variation in sugar beets and wild beets using pools of individuals. , 1997, Genome.

[5]  J. Cañón,et al.  Power analysis of QTL detection in half-sib families using selective DNA pooling , 2001, Genetics Selection Evolution.

[6]  I. Craig,et al.  Genotyping Pooled DNA on Microarrays: A Systematic Genome Screen of Thousands of SNPs in Large Samples to Detect QTLs for Complex Traits , 2004, Behavior genetics.

[7]  Hongyu Zhao,et al.  Family‐Based Association Tests for Different Family Structures Using Pooled DNA , 2005, Annals of human genetics.

[8]  A Chakravarti,et al.  Allele frequency distributions in pooled DNA samples: applications to mapping complex disease genes. , 1998, Genome research.

[9]  G. Kirov,et al.  Mutation screening and LD mapping in the VCFS deleted region of chromosome 22q11 in schizophrenia using a novel DNA pooling approach , 2002, Molecular Psychiatry.

[10]  L. Griffiths,et al.  A genetic analysis of serotonergic biosynthetic and metabolic enzymes in migraine using a DNA pooling approach , 2005, Journal of Human Genetics.

[11]  S. Ewart,et al.  Polymorphism identification within 50 equine gene-specific sequence tagged sites. , 2001, Animal genetics.

[12]  M. Feldman,et al.  Biodiversity of 52 chicken populations assessed by microsatellite typing of DNA pools , 2003, Genetics Selection Evolution.

[13]  Katarina Lindroos,et al.  Multiplex SNP genotyping in pooled DNA samples by a four-colour microarray system. , 2002, Nucleic acids research.

[14]  J. Ott,et al.  Efficiency of single-nucleotide polymorphism haplotype estimation from pooled DNA , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[15]  T. Tahira,et al.  Precise estimation of allele frequencies of single-nucleotide polymorphisms by a quantitative SSCP analysis of pooled DNA. , 2001, American journal of human genetics.

[16]  M. O’Donovan,et al.  DNA Pooling: a tool for large-scale association studies , 2002, Nature Reviews Genetics.

[17]  Robert Plomin,et al.  Genotyping DNA pools on microarrays: Tackling the QTL problem of large samples and large numbers of SNPs , 2005, BMC Genomics.

[18]  D. Clayton,et al.  Identification of the sources of error in allele frequency estimations from pooled DNA indicates an optimal experimental design. , 2002, Annals of human genetics.

[19]  Claire L. Simpson,et al.  A central resource for accurate allele frequency estimation from pooled DNA genotyped on DNA microarrays , 2005, Nucleic acids research.

[20]  D. Zeng,et al.  Estimating haplotype‐disease associations with pooled genotype data , 2005, Genetic epidemiology.

[21]  I. Craig,et al.  Single-nucleotide polymorphism genotyping in DNA pools. , 2005, Methods in molecular biology.

[22]  Hsin-Chou Yang,et al.  PDA: Pooled DNA analyzer , 2006, BMC Bioinformatics.

[23]  M. Nelson,et al.  Large-scale validation of single nucleotide polymorphisms in gene regions. , 2004, Genome research.

[24]  P. Dubreuil,et al.  Evaluation of a DNA pooled-sampling strategy for estimating the RFLP diversity of maize populations , 1999, Plant Molecular Biology Reporter.

[25]  S. Germer,et al.  High-throughput SNP allele-frequency determination in pooled DNA samples by kinetic PCR. , 2000, Genome research.

[26]  Xu Peng,et al.  BMC Bioinformatics BioMed Central Methodology article SNP haplotype tagging from DNA pools of two individuals , 2002 .

[27]  D. Cox,et al.  Application of pooled genotyping to scan candidate regions for association with HDL cholesterol levels , 2004, Human Genomics.

[28]  Matthias Wjst,et al.  Large‐scale determination of SNP allele frequencies in DNA pools using MALDI‐TOF mass spectrometry , 2002, Human mutation.

[29]  V. Sheffield,et al.  An autosomal recessive nonsyndromic-hearing-loss locus identified by DNA pooling using two inbred Bedouin kindreds. , 1996, American journal of human genetics.

[30]  Jennifer Wessel,et al.  A comprehensive literature review of haplotyping software and methods for use with unrelated individuals , 2005, Human Genomics.

[31]  B. Yakir,et al.  Quantitative technologies for allele frequency estimation of SNPs in DNA pools. , 2002, Molecular and cellular probes.

[32]  Michael Owen,et al.  Cheap, accurate and rapid allele frequency estimation of single nucleotide polymorphisms by primer extension and DHPLC in DNA pools , 2000, Human Genetics.

[33]  M.-C. Huang,et al.  A genome-wide study of preferential amplification/hybridization in microarray-based pooled DNA experiments , 2006, Nucleic acids research.

[34]  S. Weissman,et al.  An approach for global scanning of single nucleotide variations , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[35]  M. Procházka,et al.  High-throughput SNP detection by using DNA pooling and denaturing high performance liquid chromatography (DHPLC) , 2000, Human Genetics.

[36]  N Risch,et al.  The relative power of family-based and case-control designs for linkage disequilibrium studies of complex human diseases I. DNA pooling. , 1998, Genome research.

[37]  N. Arnheim,et al.  Use of pooled DNA samples to detect linkage disequilibrium of polymorphic restriction fragments and human disease: studies of the HLA class II loci. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[38]  Pak Chung Sham,et al.  Genetic Power Calculator: design of linkage and association genetic mapping studies of complex traits , 2003, Bioinform..

[39]  P. Visscher,et al.  SNP genotyping on pooled DNAs: comparison of genotyping technologies and a semi automated method for data storage and analysis. , 2002, Nucleic acids research.

[40]  Laura J. Scott,et al.  High-throughput screening for evidence of association by using mass spectrometry genotyping on DNA pools , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[41]  A DNA Pooling Strategy for Family-Based Association Studies , 2005, Cancer Epidemiology Biomarkers & Prevention.

[42]  Joni L Rutter,et al.  Efficiency of DNA pooling to estimate joint allele frequencies and measure linkage disequilibrium , 2002, Genetic epidemiology.

[43]  Hongyu Zhao,et al.  On the use of DNA pooling to estimate haplotype frequencies , 2003, Genetic epidemiology.

[44]  W. Klitz,et al.  Association mapping of disease loci, by use of a pooled DNA genomic screen. , 1997, American journal of human genetics.

[45]  Hongyu Zhao,et al.  The impacts of errors in individual genotyping and DNA pooling on association studies , 2004, Genetic epidemiology.

[46]  D. Harold,et al.  Determining SNP allele frequencies in DNA pools. , 2000, BioTechniques.

[47]  P. Sham,et al.  SNPs, microarrays and pooled DNA: identification of four loci associated with mild mental impairment in a sample of 6000 children. , 2005, Human molecular genetics.

[48]  S. P. Fodor,et al.  Genotyping over 100,000 SNPs on a pair of oligonucleotide arrays , 2004, Nature Methods.

[49]  C. Fann,et al.  A Comparison of Individual Genotyping and Pooled DNA Analysis for Polymorphism Validation Prior to Large‐Scale Genetic Studies , 2006, Annals of human genetics.

[50]  Chia-Ching Pan,et al.  New Adjustment Factors and Sample Size Calculation in a DNA-Pooling Experiment With Preferential Amplification , 2005, Genetics.

[51]  M. Owen,et al.  Streamlined analysis of pooled genotype data in SNP‐based association studies , 2005, Genetic epidemiology.

[52]  G. Shook,et al.  Identification of an ovulation rate QTL in cattle on BTA14 using selective DNA pooling and interval mapping. , 2004, Animal genetics.

[53]  M. Schalling,et al.  Pyrosequencing™‐based SNP allele frequency estimation in DNA pools , 2004, Human mutation.

[54]  Jochen Hampe,et al.  High-resolution SNP scan of chromosome 6p21 in pooled samples from patients with complex diseases. , 2003, Genomics.

[55]  P. Sham,et al.  Optimal selection strategies for QTL mapping using pooled DNA samples , 2002, European Journal of Human Genetics.

[56]  Bart M Groot,et al.  Accurate determination of microsatellite allele frequencies in pooled DNA samples , 2004, European Journal of Human Genetics.

[57]  Panos Deloukas,et al.  SNP allele frequency estimation in DNA pools and variance components analysis. , 2004, BioTechniques.

[58]  Estimation of relative allele frequencies of single-nucleotide polymorphisms in different populations by microarray hybridization of pooled DNA. , 2004, Analytical biochemistry.

[59]  Toshikazu Ito,et al.  Estimation of haplotype frequencies, linkage-disequilibrium measures, and combination of haplotype copies in each pool by use of pooled DNA data. , 2003, American journal of human genetics.

[60]  B Müller-Myhsok,et al.  Rapid simulation of P values for product methods and multiple-testing adjustment in association studies. , 2005, American journal of human genetics.

[61]  R. Strausberg,et al.  High-throughput development and characterization of a genomewide collection of gene-based single nucleotide polymorphism markers by chip-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[62]  Stefan Kammerer,et al.  Association testing by DNA pooling: An effective initial screen , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[63]  Tomas Drgon,et al.  Pooled association genome scanning: validation and use to identify addiction vulnerability loci in two samples. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[64]  D. Naiman,et al.  Polysubstance abuse-vulnerability genes: genome scans for association, using 1,004 subjects and 1,494 single-nucleotide polymorphisms. , 2001, American journal of human genetics.

[65]  P. Visscher,et al.  Simple method to analyze SNP‐based association studies using DNA pools , 2003, Genetic epidemiology.

[66]  G. Kirov,et al.  Universal, robust, highly quantitative SNP allele frequency measurement in DNA pools , 2002, Human Genetics.