University of Pittsburgh: Genetics, Genomics and Deep Phenotyping of Orofacial Clefts

The overall goal of the Pittsburgh orofacial cleft studies (POFC) is to identify genetic loci and variants involved in CL/P and associated features. Further, through a deep phenotyping paradigm (see “OFC Research Procedures Manual” and associated Forms in the Appendices) POFC investigates a wide variety of phenotypic features in individuals with OFC, their relatives, and unaffected controls. These phenotype measures more accurately define the expression of OFC in participants, and associated features can also refine gene mapping studies of OFC.

The POFC projects include simplex and extended multiplex OFC families ascertained through OFC probands at several sites in the United States (Pennsylvania, Colorado, Iowa. Missouri) and multiple international sites (Europe, Central/South America, Asia, and Africa), as well as unaffected controls.

Basic demographics, medical history, family and pregnancy history, and deep phenotyping were obtained for each research participant. (See “OFC Research Procedures Manual” and associated Appendices). Physical measurements included 3d Facial Images, dental exams, high-resolution ultrasounds of the upper lip to visualize the orbicularis oris muscle, injtra-oral photos and dental casts, height/weight, and others.

Blood or saliva samples were obtained from each study participant for DNA extraction. (See “OFC Research Procedures Manual”, Section 4.6).

To date, the DNA samples have been assessed for genome-wide SNP panels and for whole genome sequencing. See list of publications below for sample results.