Recently, more than 1000 large intergenic noncoding RNAs (lincRNAs) have been reported. These RNAs are evolutionarily conserved in mammalian genomes and thus presumably function in diverse biological processes. Here, we report the identification of lincRNAs that are regulated by p53. One of these lincRNAs (lincRNA-p21) serves as a repressor in p53-dependent transcriptional responses. Inhibition of lincRNA-p21 affects the expression of hundreds of gene targets enriched for genes normally repressed by p53. The observed transcriptional repression by lincRNA-p21 is mediated through the physical association with hnRNP-K. This interaction is required for proper genomic localization of hnRNP-K at repressed genes and regulation of p53 mediates apoptosis. We propose a model whereby transcription factors activate lincRNAs that serve as key repressors by physically associating with repressive complexes and modulate their localization to sets of previously active genes.

A Large Intergenic Noncoding RNA Induced by p53 Mediates Global Gene Repression in the p53 Response

The Brush Foundation studies on human growth and development, begun in 1931 and terminated in 1942, have been intensively reviewed and studied by Dr Greulich and Miss Pyle in the formulation of this Radiographic Atlas of Skeletal Development of the Hand and Wrist Serial radiographs of from 2 to 20 hand-films made at successive examinations of each of 1000 boys and girls made up the radiographic material Standards were selected that were judged to be the most representative of the central tendency or anatomic mode of each chronologic age group from birth through 18 years

Radiographic Atlas of Skeletal Development of the Hand and Wrist

Glaucoma is an optic neuropathy that is characterized by the progressive degeneration of the optic nerve, leading to visual impairment. Glaucoma is the main cause of irreversible blindness worldwide, but typically remains asymptomatic until very severe. Open-angle glaucoma comprises the majority of cases in the United States and western Europe, of which, primary open-angle glaucoma (POAG) is the most common type. By contrast, in China and other Asian countries, angle-closure glaucoma is highly prevalent. These two types of glaucoma are characterized based on the anatomic configuration of the aqueous humour outflow pathway. The pathophysiology of POAG is not well understood, but it is an optic neuropathy that is thought to be associated with intraocular pressure (IOP)-related damage to the optic nerve head and resultant loss of retinal ganglion cells (RGCs). POAG is generally diagnosed during routine eye examination, which includes fundoscopic evaluation and visual field assessment (using perimetry). An increase in IOP, measured by tonometry, is not essential for diagnosis. Management of POAG includes topical drug therapies and surgery to reduce IOP, although new therapies targeting neuroprotection of RGCs and axonal regeneration are under development.

Primary open-angle glaucoma.

Cytokine dysregulation is believed to play a key role in the remodeling of the immune system at older age, with evidence pointing to an inability to fine-control systemic inflammation, which seems to be a marker of unsuccessful aging. This reshaping of cytokine expression pattern, with a progressive tendency toward a pro-inflammatory phenotype has been called "inflamm-aging." Despite research there is no clear understanding about the causes of "inflamm-aging" that underpin most major age-related diseases, including atherosclerosis, diabetes, Alzheimer's disease, rheumatoid arthritis, cancer, and aging itself. While inflammation is part of the normal repair response for healing, and essential in keeping us safe from bacterial and viral infections and noxious environmental agents, not all inflammation is good. When inflammation becomes prolonged and persists, it can become damaging and destructive. Several common molecular pathways have been identified that are associated with both aging and low-grade inflammation. The age-related change in redox balance, the increase in age-related senescent cells, the senescence-associated secretory phenotype (SASP) and the decline in effective autophagy that can trigger the inflammasome, suggest that it may be possible to delay age-related diseases and aging itself by suppressing pro-inflammatory molecular mechanisms or improving the timely resolution of inflammation. Conversely there may be learning from molecular or genetic pathways from long-lived cohorts who exemplify good quality aging. Here, we will discuss some of the current ideas and highlight molecular pathways that appear to contribute to the immune imbalance and the cytokine dysregulation, which is associated with "inflammageing" or parainflammation. Evidence of these findings will be drawn from research in cardiovascular disease, cancer, neurological inflammation and rheumatoid arthritis.

/pdf/age-and-age-related-diseases-role-of-inflammation-triggers-cwvhq7tyyo.pdf

Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines.

Whole exome sequencing by high-throughput sequencing of target-enriched genomic DNA (exome-seq) has become common in basic and translational research as a means of interrogating the interpretable part of the human genome at relatively low cost. We present a comparison of three major commercial exome sequencing platforms from Agilent, Illumina and Nimblegen applied to the same human blood sample. Our results suggest that the Nimblegen platform, which is the only one to use high-density overlapping baits, covers fewer genomic regions than the other platforms but requires the least amount of sequencing to sensitively detect small variants. Agilent and Illumina are able to detect a greater total number of variants with additional sequencing. Illumina captures untranslated regions, which are not targeted by the Nimblegen and Agilent platforms. We also compare exome sequencing and whole genome sequencing (WGS) of the same sample, demonstrating that exome sequencing can detect additional small variants missed by WGS.

Performance comparison of exome DNA sequencing technologies

Screening kit for detecting high myopia

The invention discloses a test kit for detecting pathologic moyopia, comprising optionally related regents for screening relating to pathologic moyopia screening for and detecting rs2073135 variation of BAI3 genes, rs4697489 variation of CCDC149 genes, rs248014 variation, rs1105191 variation, rs1943049 variation or/and rs7035322 variation of TNC genes; and six SNP loci of a tester, including rs2073135, rs4697489, rs248014, rs1105191, rs1943049 and rs7035322 are measured to judge whether variation exists, so that the susceptibility of the tester to the pathologic moyopia are predicted The invention has the advantages of firstly, clarifying the correlation of the six SNP loci and the pathologic moyopia, having simple method for predicting the susceptibility of the pathologic moyopia, beingcapable of being applied to prevention, assistant diagnosis and cure for the pathologic moyopia and being applied to research and development of new medicines

Screening test kit for detecting pathologic moyopia

The purpose was to study the clinical features and genetics of a large Chinese family with Charcot–Marie–Tooth (CMT) disease. A genome-wide linkage scan using Applied Biosystems v. 2.5 411 short tandem repeat (STR) markers was performed in this family. Mutation screening was conducted on connexin 32 (Cx32). Prediction of impact of the mutation and sequence alignments of Cx32 in 10 vertebrates were performed using Polyphen and Clustal W, respectively. Twelve family members were diagnosed as CMT type 1. An X-chromosome locus (DXS991) was linked to the phenotype of this family by the genome-wide linkage analysis. An H100Y mutation found in Cx32 was predicted to be possibly damaging to the function of Cx32, with a PSIC score difference of 1.758. The H100 of Cx32 is highly conserved among the 10 vertebrates. A large Chinese family had CMTX1 linked to Xq13.1 caused by an H100Y mutation in the Cx32 gene. Muscle Nerve, 2010

Mutation in connexin 32 causes charcot–marie–tooth disease in a large Chinese family

Objective
To assess the association of single nucleotide polymorphisms (SNP) rs547984, rs540782, rs693421 and rs2499601 of Zona Pellucida Glycoprotein 4 (ZP4) gene with primary open-angle glaucoma (POAG) among ethnic Han Chinese from Sichuan Province.


Methods
A dye terminator-based SNaPshot method was used to genotype 336 patients with POAG and 768 healthy controls.


Results
No significant difference was detected in allelic frequencies of rs547984, rs540782, rs693421 and rs2499601 between the two groups (P>0.05). Haplotypic analysis showed a significant difference in G-G-A-G haplotype formed by the 4 SNPs between the POAG and the control groups (P<0.05).


Conclusion
ZP4 gene SNPs rs547984, rs540782, rs693421, rs2499601 are not associated with POAG among ethnic Hans from Sichuan.


Key words: 
ZP4 gene; Primary open-angle glaucoma; Single nucleotide polymorphism; Haplotype

Ying Lin

Papers

Screening kit for detecting high myopia

Screening test kit for detecting pathologic moyopia

Mutation in connexin 32 causes charcot–marie–tooth disease in a large Chinese family

Association of ZP4 gene polymorphism with primary open-angle glaucoma in an ethnic Chinese population from Sichuan province