PTCH2 is not a strong candidate gene for gorlin syndrome predisposition

A number of case/family reports have proposed PTCH2 as a putative Gorlin Syndrome (GS) gene, but evidence to support this is lacking. We assessed our cohort of 21 PTCH1/SUFU negative GS families for PTCH2 variants and assessed current evidence from reported cases/families and population data. In our PTCH1/SUFU variant negative GS cohort (25% of total), no pathogenic or likely pathogenic PTCH2 variants were identified. In addition, none of the previously published PTCH2 variants in GS families/cases could be considered pathogenic or likely pathogenic using current guidelines. The absence of clear pathogenic variants in GS families and the high frequency of Loss-of-function (LoF) variants in the general population, including the presence of homozygous LoF variants without a clinical phenotype, mean that it is untenable that PTCH2 is a GS gene. PTCH2 should not be included in panels for genetic diagnosis of GS.

ATP-Dependent Clp Protease Subunit C1, HvClpC1, Is a Strong Candidate Gene for Barley Variegation Mutant luteostrians as Revealed by Genetic Mapping and Genomic Re-sequencing

Implementation of next-generation sequencing in forward genetic screens greatly accelerated gene discovery in species with larger genomes, including many crop plants. In barley, extensive mutant collections are available, however, the causative mutations for many of the genes remains largely unknown. Here we demonstrate how a combination of low-resolution genetic mapping, whole-genome resequencing and comparative functional analyses provides a promising path toward candidate identification of genes involved in plastid biology and/or photosynthesis, even if genes are located in recombination poor regions of the genome. As a proof of concept, we simulated the prediction of a candidate gene for the recently cloned variegation mutant albostrians (HvAST/HvCMF7) and adopted the approach for suggesting HvClpC1 as candidate gene for the yellow-green variegation mutant luteostrians.

<i>UBXN1</i> is a strong candidate gene in regulation of pork water-holding capacity

The UBX domain containing protein 1-like gene (UBXN1) promotes the degradation of myofibrillar proteins during meat maturation, which affects meat water-holding capacity (WHC). This study aims to identify functional mutations in UBXN1 promoter region, which affects the transcription activity and therefore the WHC. Firstly, we confirmed that the UBXN1 expression level was positively associated with WHC. Individuals with high and low WHC (n=16 per group) were selected from 168 Duroc × Large White × Yorkshire (D × L × Y) crossbred pigs. The UBXN1 promoter region was comparatively sequenced using DNA pools from these two groups, and a mutation ca. −379T > G was revealed that had reverse allele distribution. The single nucleotide polymorphism (SNP) was then genotyped in the abovementioned population. TT genotype individuals exhibited higher UBXN1 mRNA level and higher WHC compared with GG genotype ones. Further luciferase assay confirmed that TT genotype promoter had higher activity. Moreover, the degradation of cytoskeletal framework proteins of muscle cells like desmin, synemin, dystrophin, and vinculin was higher in TT genotype individuals than GG ones. In conclusion, we identified a SNP in the UBXN1 gene promoter that contributes to WHC improvement and pork quality. And UBXN1 is a strong candidate gene in regulation of pork WHC.

Genetics of white color and iridophoroma in "Lemon Frost" leopard geckos

Coloration patterns promote survival and reproductive success in the animal kingdom. Despite their importance, wide gaps exist in our understanding of the genetic and evolutionary mechanisms that underpin them. The leopard gecko, Eublepharis macularius, is a popular companion animal, and displays a variety of coloration patterns. We investigated a spontaneous semi-dominant mutation, known as "Lemon Frost", that causes extensive white color in leopard gecko skin. Although "Lemon Frost" individuals are aesthetically appealing, more than 80% of them develop tumors of white color (i.e., iridophoroma) 0.5 to 5 years after birth. To identify the gene that regulates white color and is likely also responsible for the iridophoroma, we genotyped 220 animals, including 33 homozygous mutants, with short-read sequencing. We used synteny, linkage analysis and homozygosity mapping to localize the mutation to a strong candidate gene, SPINT1, a tumor suppressor previously implicated in human skin cutaneous melanoma (SKCM) as well as in over-proliferation of epithelial cells in mice and zebrafish. Our work establishes the leopard gecko as a tractable genetic system and suggests that a tumor suppressor in melanocytes in humans can also suppress tumor development in iridophores in lizards.

The apple columnar gene candidate MdCoL and the AP2/ERF factor MdDREB2 positively regulate ABA biosynthesis by activating the expression of MdNCED6/9

MdCoL, which encodes a putative 2OG-Fe(II) oxygenase, is a strong candidate gene for control of the columnar growth phenotype in apple. However, the mechanism by which MdCoL could produce the columnar trait is unclear. Here, we show that MdCoL influences ABA biosynthesis through its interactions with the MdDREB2 transcription factor. Expression analyses and transgenic tobacco studies confirmed that MdCoL is likely a candidate for control of the columnar phenotype. Furthermore, the ABA level in columnar apple trees is significantly higher than that in standard apple trees. A protein interaction experiment showed that MdCoL interacts with MdDREB2. Transient expression and EMSA assays demonstrated that MdDREB2 binds directly to the DRE motif in the MdNCED6 and MdNCED9 (MdNCED6/9) gene promoters, thereby activating the transcription of these ABA biosynthesis genes. In addition, a higher ABA content was detected following co-overexpression of MdCoL–MdDREB2 when compared with the overexpression of MdCoL or MdDREB2 alone. Taken together, our results indicate that an interaction between MdCoL and MdDREB2 promotes the expression of MdNCED6/9 and increases ABA levels, a phenomenon that may underlie the columnar growth phenotype in apple.

Abnormalities in extracellular glycine and glutamate levels in the striatum of sandy mice

ObjectiveGlycine regulates glutamatergic neurotransmission, and several papers have reported the relationship between glycine and schizophrenia. The dysbindin-1 (DTNBP1: dystrobrevin-binding protein 1) gene is related to glutamatergic neurotransmission and has been found to be a strong candidate gene for schizophrenia. In this study, we clarified the relationship between dysbindin, glutamate, and glycine with in vivo microdialysis methods.MethodsWe measured extracellular glycine and glutamate levels in the striatum of sandy (sdy) mice using in vivo microdialysis methods. Sdy mice express no dysbindin protein owing to a deletion in the dysbindin-1 gene. In addition, we measured changes in those amino acids after methamphetamine (METH) administration.ResultsThe basal levels of extracellular glycine and glutamate in the striatum of sdy mice were elevated. These extracellular glutamate levels decreased gradually after METH administration and were not subsequently different from those of wild-type mice.ConclusionsThese results suggest that dysbindin might modulate glycine and glutamate release in vivo.