A genome-wide study of inherited deletions identified two regions associated with nonsyndromic isolated oral clefts

Birth Defects Res A Clin Mol Teratol. 2015 Apr;103(4):276-83. doi: 10.1002/bdra.23362. Epub 2015 Mar 16.


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.

Keywords: DNA copy numbers; Oral clefts; case-parent trios; inherited deletions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosome Deletion*
  • Chromosomes, Human, Pair 7 / genetics*
  • Chromosomes, Human, Pair 8 / genetics*
  • Cleft Lip / genetics*
  • Cleft Palate / genetics*
  • DNA Copy Number Variations / genetics*
  • Genomics / methods
  • Humans
  • Inheritance Patterns / genetics*
  • Markov Chains
  • Models, Genetic