Table 3.
Recent examples of “human to animal” craniofacial studies
A select list of recent (since 2010) studies in which, first a genetic lesion is detected in a human patient with either a syndromic or non-syndromic craniofacial condition and secondarily an animal model is utilized in the same study to further understand the consequences of that lesion on craniofacial development.
| Disorder | Mutation identification approach | Gene(s) | Model organism | Assays |
|---|---|---|---|---|
| Syndromic cleft palate and micrognathia | GTG-banded karyotyping, whole- genome sequencing | CAPZB | zebrafish | Z - exp, LOF (insertional mutant), GOF (mRNA) |
| Acrofacial Dysostosis - Cincinnati Type | Whole exome sequencing, Sanger sequencing | POLR1A | zebrafish | Z - exp, LOF (insertional mutant) |
| Mandibulofacial Dysostosis with Alopecia | Trio whole exome sequencing | EDNRA | zebrafish, mouse | Z - LOF (MO), GOF (mRNA); M - exp |
| Nonsyndromic cleft lip w/ or w/o cleft palate (NSCL/P) | Targeted whole-genome sequencing | FGFR2 (+others) | zebrafish | Z - NCE-exp |
| Isolated cleft lip and palate (CLP) | Non-coding enhancer analysis | FOXE1 | zebrafish, mouse | Z - NCE-exp; M - NCE-exp |
| Van der Woude syndrome | Family-based linkage, whole exome sequencing | GRHL3 | zebrafish, mouse | Z - GOF (dn-mRNA); M - LOF |
| X-Linked Cobalamin Disorder | Whole exome sequencing, Sanger sequencing | HCFC1 | zebrafish | Z - LOF (MO) |
| Noonan syndrome | Whole exome sequencing, Sanger sequencing | RIT1 | zebrafish | Z - GOF (mutant mRNA) |
| 3MC syndrome | SNP array - homozygosity mapping | COLEC11, MASP1 | mouse, zebrafish, quail | M - exp; Z - exp, LOF (MO), GOF; Q - GOF |
Note, bold examples are reviewed in more detail in the text. Abbreviations: dn, dominant-negative; exp - expression analysis; GOF, gain-of-function; LOF, loss-of-function; M, mouse; MO, morpholino; NCE, non-coding enhancer; Q, quail; Z, zebrafish.