A predicted deleterious allele of the essential meiosis gene MND1, present in ~ 3% of East Asians, does not disrupt reproduction in mice.

Infertility is a major health problem affecting ~15% of couples worldwide. Except for cases involving readily detectable chromosome aberrations, confident identification of a causative genetic defect is problematic. Despite the advent of genome sequencing for diagnostic purposes, the preponderance of segregating genetic variants complicates identification of culprit genetic alleles or mutations. Many algorithms have been developed to predict the effects of 'variants of unknown significance', typically single nucleotide polymorphisms (SNPs), but these predictions are not sufficiently accurate for clinical action. As part of a project to identify population variants that impact fertility, we have been generating clustered regularly interspaced short palindromic repeats-Cas9 edited mouse models of suspect SNPs in genes that are known to be required for fertility in mice. Here, we present data on a non-synonymous (amino acid altering) SNP (rs140107488) in the meiosis gene Mnd1, which is predicted bioinformatically to be deleterious to protein function. We report that when modeled in mice, this allele (MND1K85M), which is present at an allele frequency of ~ 3% in East Asians, has no discernable effect upon fertility, fecundity or gametogenesis, although it may cause sex skewing of progeny from homozygous males. In sum, assuming the mouse model accurately reflects the impact of this variant in humans, rs140107488 appears to be a benign allele that can be eliminated or de-prioritized in clinical genomic analyses of infertility patients.

Biomarkers and Functional Assays of Epithelial Barrier Disruption and Gastrointestinal Dysmotility in Critical Illness-A Narrative Review.

Enteral nutrition in critically ill children has been associated with improved clinical outcomes. Gastrointestinal dysfunction often impedes the timely initiation and advancement of enteral nutrition and can contribute to immune dysregulation and systemic inflammation. Therefore, assessing gastrointestinal function, at a cellular and functional level, is important to provide optimal enteral nutrition therapy and reduce the gastrointestinal tract's contribution to the inflammatory cascade of critical illness. In this narrative review, we present an overview of biomarker and functional assays for gastrointestinal dysfunction, including epithelial barrier disruption and gastrointestinal dysmotility, that have been considered for critically ill patients.