Hypomyelinated vps16 Mutant Zebrafish Exhibit Systemic and Neurodevelopmental Pathologies.

Homotypic Fusion and Protein Sorting (HOPS) and Class C-core Vacuole/Endosome Tethering (CORVET) complexes regulate the correct fusion of endolysosomal bodies. Mutations in core proteins (VPS11, VPS16, VPS18, and VPS33) have been linked with multiple neurological disorders, including mucopolysaccharidosis (MPS), genetic leukoencephalopathy (gLE), and dystonia. Mutations in human Vacuolar Protein Sorting 16 (VPS16) have been associated with MPS and dystonia. In this study, we generated and characterized a zebrafish vps16(-/-) mutant line using immunohistochemical and behavioral approaches. The loss of Vps16 function caused multiple systemic defects, hypomyelination, and increased neuronal cell death. Behavioral analysis showed a progressive loss of visuomotor response and reduced motor response and habituation to acoustic/tap stimuli in mutants. Finally, using a novel multiple-round acoustic/tap stimuli test, mutants showed intermediate memory deficits. Together, these data demonstrate that zebrafish vps16(-/-) mutants show systemic defects, neurological and motor system pathologies, and cognitive impairment. This is the first study to report behavior abnormalities and memory deficiencies in a zebrafish vps16(-/-) mutant line. Finally, we conclude that the deficits observed in vps16(-/-) zebrafish mutants do not mimic pathologies associated with dystonia, but more align to abnormalities associated with MPS and gLE.

Family-based GWAS for dental class I malocclusion and clefts.

BACKGROUND: Individuals born with cleft lip and/or palate who receive corrective surgery regularly have abnormal growth in the midface region such that they exhibit premaxillary hypoplasia. However, there are also genetic contributions to craniofacial morphology in the midface region, so although these individuals appear to have Class III skeletal discrepancy, their molar relationship may be Class I. Past genome-wide association studies (GWASs) on skeletal Class II and III malocclusion suggested that multiple genetic markers contribute to these phenotypes via a multifactorial inheritance model, but research has yet to examine the genetic markers associated with dental Class I malocclusion. Thus, our goal was to conduct a family based GWAS to identify genes across the genome that are associated with Class I malocclusion, as defined by molar relations, in humans with and without clefts. METHODS: Our cohort consisted of 739 individuals from 47 Filipino families originally recruited in 2006 to investigate the genetic basis of orofacial clefts. All individuals supplied blood samples for DNA extraction and genotyping, and a 5,766 single nucleotide polymorphism (SNP) custom panel was used for the analyses. We performed a transmission disequilibrium test for participants with and without clefts to identify genetic contributors potentially involved with Class I malocclusion. RESULTS: In the total cohort, 13 SNPs had associations that reached the genomic control threshold (p < 0.005), while five SNPs were associated with Class I in the cohort of participants without clefts, including four associations that were identified in the total cohort. The associations for the SNPs ABCA4 rs952499, SOX1-OT rs726455, and RORA rs877228 are of particular interest, as past research found associations between these genes and various craniofacial phenotypes, including cleft lip and/or palate. CONCLUSIONS: These findings support the multifactorial inheritance model for dental Class I malocclusion and suggest a common genetic basis for different aspects of craniofacial development.

Examining Relations Between Parental Feedback Types and Preschool-Aged Children's Academic Skills.

Prior research has shown associations between parent and teacher feedback and school-aged children's academic outcomes. Specifically, studies have demonstrated that positive feedback (i.e., praise and/or affirmation) is beneficial for children's academic outcomes, while corrective feedback exhibits more mixed associations with children's academic outcomes. Little is known about the relations between parental feedback and younger children's academic skills. The present study examines the frequency of positive and corrective types of feedback provided by parents of 4-year-old children during semi-structured interactions, as well as how these feedback types relate to children's concurrent math and language skills and their change in math skills over a one-year period. Parent-child dyads (n=91) were observed interacting with a picture book, grocery store set, and magnet board puzzle for 5 to 10 minutes each, after which they completed math and language assessments. Parental affirmation was positively and corrective feedback was negatively associated with children's concurrent math outcomes, but only corrective feedback was uniquely negatively associated with children's math outcomes when controlling for affirmations. Parental praise was individually and uniquely positively associated with children's expressive vocabulary and change in math outcomes from age 4 to age 5. This study suggests that the relations between parental feedback and young children's academic outcomes depend on the type of feedback and the outcome of interest (i.e., math vs language), which can inform how parents may want to provide feedback to facilitate learning.