Haplo-essential genes are those which cannot tolerate a loss-of-function (LoF) mutation in a single allele. These essential genes are critical for cell survival (cell essential) and organism development (developmental essential). De novo LoF mutations of halpo-essential genes, therefore, likely contribute to reproductive failure in humans. Recently, Nucleolar protein 6 (Nol6), a protein coding gene, has been identified as an ideal candidate for phenotypic expansion for exploring genetic variants related to stillbirth . Mouse embryos were edited via CRISPR/Cas9 reagents to induce a heterozygous LoF mutation in Nol6, followed by in vitro culture to blastocyst stage to experimentally assess haplo-essentiality. Phenotype was annotated using an embryoscope and was correlated to genotype obtained by Sanger sequencing. Fisher exact tests and Wilcoxon Sum Ranked tests were used to statistically analyze results.
Gonzalez, Alexandria N., "Phenotypic expansion of nucleolar protein 6, a potential haplo-essential gene contributing to reproductive failure" (2021). MEDI 8127 Scholarly Activities Pre-Clerkship. 7.