title: Novel copy-number variants in a population-based investigation of classic heterotaxy.
abstract: OBJECTIVE
  Heterotaxy is a clinically and genetically heterogeneous disorder. We investigated whether screening cases restricted to a classic phenotype would result in the discovery of novel, potentially causal copy-number variants.
  
  
  METHODS
  We identified 77 cases of classic heterotaxy from all live births in New York State during 1998-2005. DNA extracted from each infant's newborn dried blood spot was genotyped with a microarray containing 2.5 million single-nucleotide polymorphisms. Copy-number variants were identified with PennCNV and cnvPartition software. Candidates were selected for follow-up if they were absent in unaffected controls, contained 10 or more consecutive probes, and had minimal overlap with variants published in the Database of Genomic Variants.
  
  
  RESULTS
  We identified 20 rare copy-number variants including a deletion of BMP2, which has been linked to laterality disorders in mice but not previously reported in humans. We also identified a large, terminal deletion of 10q and a microdeletion at 1q23.1 involving the MNDA gene; both are rare variants suspected to be associated with heterotaxy.
  
  
  CONCLUSIONS
  Our findings implicate rare copy-number variants in classic heterotaxy and highlight several candidate gene regions for further investigation. We also demonstrate the efficacy of copy-number variant genotyping in blood spots using microarrays.
authors.affiliation: 1] Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA [2] Department of Neonatology, Walter Reed National Military Medical Center, Bethesda, Maryland, USA.
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Rigler
authors.affiliation: Division of Genetics, Wadsworth Center, New York State Department of Health, Albany, New York, USA.
authors.forename: Denise M
authors.initials: DM
authors.lastname: Kay
authors.affiliation: Division of Genetics, Wadsworth Center, New York State Department of Health, Albany, New York, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Sicko
authors.affiliation: Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA.
authors.forename: Ruzong
authors.initials: R
authors.lastname: Fan
authors.affiliation: Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA.
authors.forename: Aiyi
authors.initials: A
authors.lastname: Liu
authors.affiliation: Division of Genetics, Wadsworth Center, New York State Department of Health, Albany, New York, USA.
authors.forename: Michele
authors.initials: M
authors.lastname: Caggana
authors.affiliation: 1] Congenital Malformations Registry, New York State Department of Health, Albany, New York, USA [2] Department of Epidemiology and Biostatistics, University at Albany School of Public Health, Rensselaer, New York, USA.
authors.forename: Marilyn L
authors.initials: ML
authors.lastname: Browne
authors.affiliation: 1] Congenital Malformations Registry, New York State Department of Health, Albany, New York, USA [2] Department of Epidemiology and Biostatistics, University at Albany School of Public Health, Rensselaer, New York, USA.
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Druschel
authors.affiliation: Department of Epidemiology, College of Public Health, The University of Iowa, Iowa City, Iowa, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Romitti
authors.affiliation: Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA.
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Brody
authors.affiliation: Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA.
authors.forename: James L
authors.initials: JL
authors.lastname: Mills
mesh_terms: D016022:Case-Control Studies; D055028:Comparative Genomic Hybridization; D000013:Congenital Abnormalities / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D056915:DNA Copy Number Variations; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009518:New York / Q000453:epidemiology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011159:Population Surveillance; D012307:Risk Factors; D017384:Sequence Deletion