CNGB1

The timing of vegetative phase change (VPC) in plants is regulated by a temporal decline in the expression of miR156. Both exogenous cues and endogenous factors, such as temperature, light, sugar, nutrients, and epigenetic regulators, have been shown to affect VPC by altering miR156 expression. However, the genetic basis of natural variation in VPC remains largely unexplored. Here, we conducted a genome-wide association study on the variation of the timing of VPC in Arabidopsis. We identified CYCLIC NUCLEOTIDE-GATED ION CHANNEL 4 (CNGC4) as a significant locus associated with the diversity of VPC. Mutations in CNGC4 delayed VPC, accompanied by an increased expression level of miR156 and a corresponding decrease in SQUAMOSA PROMOTER BINDING-LIKE (SPL) gene expression. Furthermore, mutations in CNGC2 and CATION EXCHANGER 1/3 (CAX1/3) also led to a delay in VPC. Polymorphisms in the CNGC4 promoter contribute to the natural variation in CNGC4 expression and the diversity of VPC. Specifically, the early CNGC4 variant promotes VPC and enhances plant adaptation to local environments. In summary, our findings offer genetic insights into the natural variation in VPC in Arabidopsis, and reveal a previously unidentified role of calcium signaling in the regulation of VPC.

The profitability of the beef cattle production system relies heavily on reproductive traits. Unfortunately, certain traits, such as age at first calving (AFC), calving interval (CI), and gestation length (GL), can pose challenges in traditional breeding programs because of their low heritability (0.01-0.12) and sex-limited characteristics. Another important aspect is the conservation of the genetic resources of animals adapted to the Colombian regions, which implies the preservation and rational use of the creole breeds in the country market. Therefore, this study aimed to identify genomic regions in the creole cattle breed Blanco Orejinegro (BON) that influence the reproductive traits in females. The dataset comprised 439 animals and 118,116 single-nucleotide polymorphisms' (SNPs) markers. The GS3 program was used to identify the SNP effects employing the BAYES Cπ methodology. The number of SNPs with effect for AFC was 25, 1527 for CI, and 23 for GL. Some of the genes found associated with reproductive and growth traits as well as immune response and environmental adaptation ECE1, EPH, EPHB2, SMARCAL1, IGFBP5, IGFBP2, FCGRT, EGFR, MUL1, PINK1, STPG1, CNGB1, TGFB1, OXTR, IL22RA1, MYOM3, OXTR, CNR2, HIVEP3, CTPS1, CXCL8, FCGRT, MREG, TMEM169, PECR, and MC1R. Our results evidenced a high contribution of the genetic architecture of the Colombian creole cattle breed Blanco Orejinegro that may impact should be included in implementing genetic improvement and conservation programs.

In this study we investigated a gene augmentation therapy candidate for the treatment of retinitis pigmentosa (RP) due to cyclic nucleotide-gated channel beta 1 (CNGB1) mutations. We used an adeno-associated virus serotype 5-with transgene under control of a novel short human rhodopsin promoter. The promoter/capsid combination drove efficient expression of a reporter gene (AAV5-RHO-eGFP) exclusively in rod photoreceptors in primate, dog and mouse following subretinal delivery. The therapeutic vector (AAV5-RHO-CNGB1) delivered to the subretinal space of CNGB1 mutant dogs restored rod-mediated retinal function (electroretinographic responses and vision) for at least 12 months post treatment. Immunohistochemistry showed human CNGB1 was expressed in rod photoreceptors in the treated regions as well as restoration of expression and trafficking of the endogenous alpha subunit of the rod CNG channel required for normal channel formation. The treatment reversed abnormal accumulation of the second messenger, cyclic guanosine monophosphate, that occurs in rod photoreceptors of CNGB1 mutant dogs, confirming formation of a functional CNG channel. In vivo imaging showed long-term preservation of retinal structure. In conclusion, this study establishes the long-term efficacy of subretinal delivery of AAV5-RHO-CNGB1 to rescue the disease phenotype in a canine model of CNGB1-RP confirming its suitability for future clinical development.