title: A genome-wide study of inherited deletions identified two regions associated with nonsyndromic isolated oral clefts.
abstract: BACKGROUND
  DNA copy number variants play an important part in the development of common birth defects such as oral clefts. Individual patients with multiple birth defects (including oral clefts) have been shown to carry small and large chromosomal deletions.
  
  
  METHODS
  We investigated the role of polymorphic copy number deletions by comparing transmission rates of deletions from parents to offspring in case-parent trios of European ancestry ascertained through a cleft proband with trios ascertained through a normal offspring. DNA copy numbers in trios were called using the joint hidden Markov model in the freely available PennCNV software. All statistical analyses were performed using Bioconductor tools in the open source environment R.
  
  
  RESULTS
  We identified a 67 kb region in the gene MGAM on chromosome 7q34, and a 206 kb region overlapping genes ADAM3A and ADAM5 on chromosome 8p11, where deletions are more frequently transmitted to cleft offspring than control offspring.
  
  
  CONCLUSIONS
  These genes or nearby regulatory elements may be involved in the etiology of oral clefts.
authors.affiliation: Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore.
authors.forename: Samuel G
authors.initials: SG
authors.lastname: Younkin
authors.forename: Robert B
authors.initials: RB
authors.lastname: Scharpf
authors.forename: Holger
authors.initials: H
authors.lastname: Schwender
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Parker
authors.forename: Alan F
authors.initials: AF
authors.lastname: Scott
authors.forename: Mary L
authors.initials: ML
authors.lastname: Marazita
authors.forename: Terri H
authors.initials: TH
authors.lastname: Beaty
authors.forename: Ingo
authors.initials: I
authors.lastname: Ruczinski
mesh_terms: D002872:Chromosome Deletion; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D056915:DNA Copy Number Variations / Q000235:genetics*; D023281:Genomics / Q000379:methods; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics*; D008390:Markov Chains; D008957:Models, Genetic
keywords: DNA copy numbers; Oral clefts; case-parent trios; inherited deletions