Methylation of KvDMR1 involved in regulating the imprinting of CDKN1C gene in cattle

The CDKN1C gene encodes a cyclin‐dependent kinase inhibitor and is one of the key genes involved in the development of Beckwith–Wiedemann syndrome and cancer. In this study, using a direct sequencing approach based on a single nucleotide polymorphism (SNP) at genomic DNA and cDNA levels, we show that CDKN1C exhibits monoallelic expression in all seven studied organs (heart, liver, spleen, lung, kidney, muscle and subcutaneous fat) in cattle. To investigate how methylation regulates imprinting of CDKN1C in cattle, allele‐specific methylation patterns in two putative differential methylation regions (DMRs), the CDKN1C DMR and KvDMR1, were analyzed in three tissues (liver, spleen and lung) using bisulfite sequencing PCR. Our results show that in the CDKN1C DMR both parental alleles were unmethylated in all three analyzed tissues. In contrast, KvDMR1 was differentially methylated between the two parental alleles in the same tissues. Statistical analysis showed that there is a significant difference in the methylation level between the two parental alleles (P < 0.01), confirming that this region is the DMR of KvDMR1 and that it may be correlated with CDKN1C imprinting.     

A testis‐specific gene within a widely expressed gene: Contrasting evolutionary patterns of two differentially expressed mammalian proteins encoded by a single gene,CAMK4

Understanding the patterns of genetic variations within fertility‐related genes and the evolutionary forces that shape such variations is crucial in predicting the fitness landscapes of subsequent generations. This study reports distinct evolutionary features of two differentially expressed mammalian proteins [CaMKIV (Ca²⁺/calmodulin‐dependent protein kinase IV) and CaS (calspermin)] that are encoded by a single gene, CAMK4. The multifunctional CaMKIV, which is expressed in multiple tissues including testis and ovary, is evolving at a relatively low rate (0.46–0.64 × 10^?9 nucleotide substitutions/site/year), whereas the testis‐specific CaS gene, which is predominantly expressed in post‐meiotic cells, evolves at least three to four times faster (1.48–1.98 × 10^?9 substitutions/site/year). Concomitantly, maximum‐likelihood‐based selection analyses revealed that the ubiquitously expressed CaMKIV is constrained by intense purifying selection and, therefore, remained functionally highly conserved throughout the mammalian evolution, whereas the testis‐specific CaS gene is under strong positive selection. The substitution rates of different mammalian lineages within both genes are positively correlated with GC content, indicating the possible influence of GC‐biased gene conversion on the estimated substitution rates. The observation of such unusually high GC content of the CaS gene (≈74%), particularly in the lineage that comprises the bovine species, suggests the possible role of GC‐biased gene conversion in the evolution of CaS that mimics positive selection.     

Accuracy of predicting genomic breeding values for carcass merit traits in Angus and Charolais beef cattle

Accuracy of predicting genomic breeding values for carcass merit traits including hot carcass weight, longissimus muscle area (REA), carcass average backfat thickness (AFAT), lean meat yield (LMY) and carcass marbling score (CMAR) was evaluated based on 543 Angus and 400 Charolais steers genotyped on the Illumina BovineSNP50 Beadchip. For the genomic prediction within Angus, the average accuracy was 0.35 with a range from 0.32 (LMY) to 0.37 (CMAR) across different training/validation data‐splitting strategies and statistical methods. The within‐breed genomic prediction for Charolais yielded an average accuracy of 0.36 with a range from 0.24 (REA) to 0.46 (AFAT). The across‐breed prediction had the lowest accuracy, which was on average near zero. When the data from the two breeds were combined to predict the breeding values of either breed, the prediction accuracy averaged 0.35 for Angus with a range from 0.33 (REA) to 0.39 (CMAR) and averaged 0.33 for Charolais with a range from 0.18 (REA) to 0.46 (AFAT). The prediction accuracy was slightly higher on average when the data were split by animal's birth year than when the data were split by sire family. These results demonstrate that the genetic relationship or relatedness of selection candidates with the training population has a great impact on the accuracy of predicting genomic breeding values under the density of the marker panel used in this study.     

10-Year Overview of the Hospital-Based Prevalence and Treatment of Congenital Cataracts: The CCPMOH Experience

A review of 6 years of hospitalization charts from Zhongshan Ophthalmic Center (ZOC) revealed that congenital cataracts (CC) accounted for 2.39% of all cataract in-patient cases and that the age at surgery was decreasing before the establishment of the Childhood Cataract Program of the Chinese Ministry of Health (CCPMOH) in December 2010. We aimed to investigate data from the 4 years (January 2011 to December 2014) following the establishment of the CCPMOH, compared, and combined with data from the previous study period (January 2005 to December 2010) to generate a 10-year overview of the hospital-based prevalence and treatment of CC. In the 4-year period after CCPMOH establishment, the prevalence of CC was 2.01% in all hospitalizations, and was 2.78% in all cataract in-patients. Most of the eligible CC in-patients (71%) lived in south China. The ratio of boys to girls was 1.42:1. Nearly 2/3 of the patients underwent cataract extraction with primary intraocular lens (IOL) implantation at a mean age of 78.40±51.45 months, and cataract extraction surgeries without IOL implantation were performed in the remaining 1/3 of patients at a mean age of 10.03±15.92 months. After CCPMOH establishment, an increased incidence of CC was revealed, and the CC in-patients were younger than the patients in the previous period. The 10-year overview (2421 CC in-patients from 206630 hospitalizations) revealed upward trends in both the number and the prevalence of CC and a further reduction in age at surgery. In conclusion, the data from 4-year period after CCPMOH establishment and the 10-year overview showed upward trends in the hospital-based prevalence of CC cases and a further reduction in age at surgery, likely reflecting the effects of the CCPMOH establishment and providing useful information for further CC studies and a valuable foundation for the prevention and treatment of this cause of childhood blindness.     

Acquisition of an additional internal cleavage site differentially affects the ability of pseudorabies virus to multiply in different host cells.

The translocation of the 325 leftmost bp of the genome of pseudorabies virus (PrV) to the internal junction between the L and S components confers upon the virus a growth advantage relative to wild-type PrV in chicken embryo fibroblasts (CEFs) and chickens and a growth disadvantage in rabbit kidney (RK) cells and mice. To clarify the molecular basis for the species-specific growth characteristics of the translocation mutants, we have compared several parameters of the virus growth cycle in CEFs and RK cells infected with wild-type PrV and with translocation mutants. The salient findings are as follows. (i) The synthesis of early-late and late proteins is not as effective in CEFs as it is in RK cells, and these proteins, in particular, the major capsid proteins, accumulate less abundantly in CEFs than in RK cells. (ii) Cleavage of concatemeric DNA to genome-size molecules is also not as effective in CEFs as it is in RK cells. (iii) The internal junction present in translocation mutants is a functional cleavage site. (iv) In RK cells, translocation mutants are hypercleaved and a significant proportion of the total viral DNA is cleaved into subgenomic fragments. (v) In CEFs infected with translocation mutants, subgenomic fragments also accumulate but most of the viral DNA remains in concatemeric form. A model which postulates that the cell-specific growth advantage or disadvantage of the translocation mutants is related to the presence of a second cleavage site within their genomes and is affected by the efficiency of cleavage of concatemeric DNA in particular infected cell types is presented. The significance of these findings as they relate to the evolution of herpesviruses with class 2- and class 3-like genomes is discussed.