Date of Award
Medical Doctor (MD)
Leo R. Otake
Cleft lip and palate deformities, occurring independently or simultaneously, affect approximately 1 in 750 births with variances in incidence noted between ethnic groups. While many environmental factors have been implicated in the development of this congenital orofacial malformation, the influence of genetics on its manifestation remains largely speculative and abstract. Pedigree analyses strongly suggest a genetic component to clefting as the malformation often recurs among siblings and within familial lineages. In this study we examine the genetic sequences of a cohort of 44 individuals (offspring of consanguineous unions) from Amman, Jordan with nonsyndromic clefting of the lip/palate to determine if there are any genetic aberrations present that may be liked to the observed phenotype. DNA samples were collected using buccal swabs and subsequently amplified by PCR. The amplified DNA was hybridized on Illumina 610 Quad microarray chips and the resultant data analyzed to determine the genetic sequence of each subject. The genetic sequences were then analyzed using Combined CNV and BeadStudio algorithms to identify variations in the genomes based single nucleotide polymorphisms (SNPs) and copy number variations (CNVs). Our studies found a 170 base pair homozygous deletion on chromosome 5 with a cadherin 9 (CDH9) gene flanking its 5' region. This deletion may serve as a potential genetic marker for orofacial clefting and may lend considerable insight into the pathways associated with early human development and may prove useful in determining novel therapeutic approaches for treatment of the malformation.
Mcintosh, Lionel Sennacherib, "Novel 170 Base Pair Homozygous Deletion Associated With Cadherin 9 Gene On Chromosome 5 May Serve As A Marker For Cleft Lip And Palate Deformities." (2011). Yale Medicine Thesis Digital Library. 1577.