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Genetics and environment interact synergistically to modulate craniofacial disease phenotypes
Author(s) -
Eberhart Johann,
Swartz Mary
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.180.6
Subject(s) - pdgfra , craniofacial , zebrafish , biology , craniofacial abnormality , haploinsufficiency , phenotype , heterozygote advantage , genetics , mutant , neural crest , gene , cancer research , allele , gist , stromal cell
Craniofacial disease can result from genetic or environmental factors and disease phenotypes can vary greatly between individuals with common underlying factors. A cause of this variability is gene‐environment interactions; our objective is to determine the nature of these interactions. We performed an "interaction screen", where we treated zebrafish embryos carrying mutant copies of genes that regulate craniofacial development with ethanol, a teratogen known to cause craniofacial defects. We found ethanol strongly interacts with the pdgfra locus. Under normal conditions, homozygous pdgfra mutants have cleft palate while pdgfra heterozygotes develop normally. Following ethanol treatment, pdgfra homozygous mutants lose the majority of the craniofacial skeleton and pdgfra heterozygotes have palatal defects, displaying latent haploinsufficiency. Importantly, the phenotype of ethanol treated fish does not appear to be due to the same mechanism causing defects in untreated pdgfra mutants. Untreated pdgfra mutants have cleft palate due to the failure of crest cells to appropriately migrate to the oral ectoderm. However, craniofacial defects in ethanol treated pdgfra mutants and heterozygotes appear to be due, at least partly, to an increase in cell death. Our results suggest that gene‐environment interactions can be synergistic, adding complexity to the etiology of craniofacial disease.