Modifiers of Cardiac Phenotypes

Modifiers of Cardiac Phenotypes.

Divergent phenotypes in Gaucher disease implicate the role of modifiers.

BACKGROUND Gaucher disease is classified into neuronopathic and non-neuronopathic forms with wide phenotypic variation among patients sharing the same genotype. While homozygosity for the common L444P allele usually correlates with the neuronopathic forms, how a defined genotype leads to a phenotype remains unknown. METHODS The genetic and epigenetic factors causing phenotypic differences wer...

Genetic modifiers of otocephalic phenotypes in Otx2 heterozygous mutant mice.

Mice heterozygous for the Otx2 mutation display a craniofacial malformation, known as otocephaly or agnathia-holoprosencephaly complex. The severity of the phenotype is dependent on the genetic background of a C57BL/6 (B6) strain; most of the offspring of Otx2 knock-out chimeras, which are equivalent to the F(1) of CBA and B6 strains, backcrossed with B6 females display reduction or loss of man...

Heterogeneity of genetic modifiers ensures normal cardiac development.

BACKGROUND Mutations of the transcription factor Nkx2-5 cause pleiotropic heart defects with incomplete penetrance. This variability suggests that additional factors can affect or prevent the mutant phenotype. We assess here the role of genetic modifiers and their interactions. METHODS AND RESULTS Heterozygous Nkx2-5 knockout mice in the inbred strain background C57Bl/6 frequently have atrial...

Genetics Heterogeneity of Genetic Modifiers Ensures Normal Cardiac Development

Background—Mutations of the transcription factor Nkx2-5 cause pleiotropic heart defects with incomplete penetrance. This variability suggests that additional factors can affect or prevent the mutant phenotype. We assess here the role of genetic modifiers and their interactions. Methods and Results—Heterozygous Nkx2-5 knockout mice in the inbred strain background C57Bl/6 frequently have atrial a...