Array-based DNA diagnostics: let the revolution begin.

Advances in the fabrication of DNA microarrays as well as transformations in detection chemistries have vastly increased the throughput for genotyping, DNA sequencing, and array-based copy number analysis (ABCNA). Rapid changes in technology are not only affecting research but also revolutionizing DNA diagnostics. Here we focus on the application of high-throughput ABCNA and genotyping. Targeted and genome-wide ABCNA has led to the discovery of extensive DNA copy number variation in the population and the delineation of many previously unrecognized submicroscopic chromosomal aberrations (genomic disorders). High-throughput single-nucleotide polymorphism (SNP) genotyping is being widely applied in genome-wide association studies (GWASs) with recent successes in identification of common variants that confer risk for common adult diseases. Future applications of high-throughput genotyping and array-based DNA sequencing technology will undoubtedly involve research and diagnostic analyses of rare mutations and perhaps ultimately enable full individual genome sequencing.

[1]  M. Jarvelin,et al.  A Common Variant in the FTO Gene Is Associated with Body Mass Index and Predisposes to Childhood and Adult Obesity , 2007, Science.

[2]  Pawel Stankiewicz,et al.  Genomic disorders : the genomic basis of disease , 2006 .

[3]  Thomas LaFramboise,et al.  Sensitive mutation detection in heterogeneous cancer specimens by massively parallel picoliter reactor sequencing , 2006, Nature Medicine.

[4]  Ronald W. Davis,et al.  Multiplexed genotyping with sequence-tagged molecular inversion probes , 2003, Nature Biotechnology.

[5]  Sinead B. O'Leary,et al.  Genetic variation in the 5q31 cytokine gene cluster confers susceptibility to Crohn disease , 2001, Nature Genetics.

[6]  P. Fearnhead,et al.  Genome-wide association study of prostate cancer identifies a second risk locus at 8q24 , 2007, Nature Genetics.

[7]  M. Daly,et al.  Genome-wide association studies for common diseases and complex traits , 2005, Nature Reviews Genetics.

[8]  Mourad Sahbatou,et al.  Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease , 2001, Nature.

[9]  S. Hober,et al.  Pyrosequencing: history, biochemistry and future. , 2006, Clinica chimica acta; international journal of clinical chemistry.

[10]  K. Gunderson,et al.  High-resolution genomic profiling of chromosomal aberrations using Infinium whole-genome genotyping. , 2006, Genome research.

[11]  T. Hudson,et al.  A genome-wide association study identifies novel risk loci for type 2 diabetes , 2007, Nature.

[12]  Judy H. Cho,et al.  A Genome-Wide Association Study Identifies IL23R as an Inflammatory Bowel Disease Gene , 2006, Science.

[13]  L. Shaffer,et al.  Targeted genomic microarray analysis for identification of chromosome abnormalities in 1500 consecutive clinical cases. , 2006, The Journal of pediatrics.

[14]  Andrew J Sharp,et al.  Discovery of previously unidentified genomic disorders from the duplication architecture of the human genome , 2006, Nature Genetics.

[15]  E. Eichler,et al.  Linkage disequilibrium and heritability of copy-number polymorphisms within duplicated regions of the human genome. , 2006, American journal of human genetics.

[16]  D. Clayton,et al.  A genome-wide association study of nonsynonymous SNPs identifies a type 1 diabetes locus in the interferon-induced helicase (IFIH1) region , 2006, Nature Genetics.

[17]  H. Engeland,et al.  Identification of novel autism candidate regions through analysis of reported cytogenetic abnormalities associated with autism , 2006, Molecular Psychiatry.

[18]  Kenny Q. Ye,et al.  Strong Association of De Novo Copy Number Mutations with Autism , 2007, Science.

[19]  M. Metzker.  Emerging technologies in DNA sequencing. , 2005, Genome research.

[20]  Marcia M. Nizzari,et al.  Genome-Wide Association Analysis Identifies Loci for Type 2 Diabetes and Triglyceride Levels , 2007, Science.

[21]  James R. Knight,et al.  Genome sequencing in microfabricated high-density picolitre reactors , 2005, Nature.

[22]  Fuli Yu,et al.  Highly multiplexed molecular inversion probe genotyping: over 10,000 targeted SNPs genotyped in a single tube assay. , 2005, Genome research.

[23]  D. Gudbjartsson,et al.  Genome-wide association study identifies a second prostate cancer susceptibility variant at 8q24 , 2007, Nature Genetics.

[24]  A. Oliphant,et al.  BeadArray technology: enabling an accurate, cost-effective approach to high-throughput genotyping. , 2002, BioTechniques.

[25]  Pawel Stankiewicz,et al.  Use of array CGH in the evaluation of dysmorphology, malformations, developmental delay, and idiopathic mental retardation. , 2007, Current opinion in genetics & development.

[26]  G. Abecasis,et al.  A Genome-Wide Association Study of Type 2 Diabetes in Finns Detects Multiple Susceptibility Variants , 2007, Science.

[27]  Alastair Forbes,et al.  Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn's disease susceptibility , 2007, Nature Genetics.

[28]  Simon C. Potter,et al.  Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls , 2007, Nature.

[29]  M. McCarthy,et al.  Replication of Genome-Wide Association Signals in UK Samples Reveals Risk Loci for Type 2 Diabetes , 2007, Science.

[30]  J. Cruysberg,et al.  Microarray-based mutation detection and phenotypic characterization of patients with Leber congenital amaurosis. , 2006, Investigative ophthalmology & visual science.

[31]  Z. Ou,et al.  Clinical Implementation of Chromosomal Microarray Analysis: Summary of 2513 Postnatal Cases , 2007, PloS one.

[32]  E. Eichler,et al.  Segmental duplications and copy-number variation in the human genome. , 2005, American journal of human genetics.

[33]  A. Beaudet,et al.  Comparative genomic hybridization and prenatal diagnosis , 2006, Current opinion in obstetrics & gynecology.

[34]  B. Ylstra,et al.  BAC to the future! or oligonucleotides: a perspective for micro array comparative genomic hybridization (array CGH) , 2006, Nucleic acids research.

[35]  E. Shuster.  Microarray genetic screening: a prenatal roadblock for life? , 2007, The Lancet.

[36]  R Redon,et al.  Array-based comparative genomic hybridisation identifies high frequency of cryptic chromosomal rearrangements in patients with syndromic autism spectrum disorders , 2006, Journal of Medical Genetics.

[37]  R. A. Bailey,et al.  Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes , 2007, Nature Genetics.

[38]  Dustin E. Schones,et al.  High-Resolution Profiling of Histone Methylations in the Human Genome , 2007, Cell.

[39]  D. Conrad,et al.  Global variation in copy number in the human genome , 2006, Nature.

[40]  Charles Lee,et al.  Genome-wide detection of human copy number variations using high-density DNA oligonucleotide arrays. , 2006, Genome research.

[41]  Beverley Balkau,et al.  Variation in FTO contributes to childhood obesity and severe adult obesity , 2007, Nature Genetics.

[42]  W. Willett,et al.  A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer , 2007, Nature Genetics.

[43]  J. Lupski,et al.  Genotyping microarray (gene chip) for the ABCR (ABCA4) gene , 2003, Human mutation.

[44]  F. Hu,et al.  A Common Genetic Variant Is Associated with Adult and Childhood Obesity , 2006, Science.

[45]  J. Ott,et al.  Complement Factor H Polymorphism in Age-Related Macular Degeneration , 2005, Science.

[46]  Simon Heath,et al.  Novel Crohn Disease Locus Identified by Genome-Wide Association Maps to a Gene Desert on 5p13.1 and Modulates Expression of PTGER4 , 2007, PLoS genetics.

[47]  C. Barnstable,et al.  HTRA1 Promoter Polymorphism in Wet Age-Related Macular Degeneration , 2006, Science.

[48]  Kevin L. Gunderson,et al.  Highly parallel genomic assays , 2006, Nature Reviews Genetics.

[49]  S. P. Fodor,et al.  Large-scale genotyping of complex DNA , 2003, Nature Biotechnology.

[50]  Pawel Stankiewicz,et al.  Genomic Disorders: Molecular Mechanisms for Rearrangements and Conveyed Phenotypes , 2005, PLoS genetics.

[51]  K. Mossman.  The Wellcome Trust Case Control Consortium, U.K. , 2008 .

[52]  N. Camp,et al.  A Variant of the HTRA1 Gene Increases Susceptibility to Age-Related Macular Degeneration , 2006, Science.

[53]  Thomas Lengauer,et al.  A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1 , 2007, Nature Genetics.

[54]  Aravinda Chakravarti,et al.  DNA duplication associated with Charcot-Marie-Tooth disease type 1A , 1991, Cell.

[55]  A. Beaudet.  Autism: highly heritable but not inherited , 2007, Nature Medicine.

[56]  Andres Metspalu,et al.  Simultaneous Multigene Mutation Detection in Patients With Sensorineural Hearing Loss Through a Novel Diagnostic Microarray: A New Approach for Newborn Screening Follow-up , 2006, Pediatrics.