Parallel shift of DNA methylation and gene expression toward the mean in mouse spleen with aging.

Age-associated DNA-methylation drift (AMD) manifests itself in two ways in mammals: global decrease (hypomethylation) and local increase of DNA methylation (hypermethylation). To comprehend the principle behind this bidirectional AMD, we studied methylation states of spatially clustered CpG dinucleotides in mouse splenic DNA using reduced-representation-bisulfite-sequencing (RRBS). The mean methylation levels of whole CpGs declined with age.

Widespread somatic L1 retrotransposition in normal colorectal epithelium.

Throughout an individual's lifetime, genomic alterations accumulate in somatic cells. However, the mutational landscape induced by retrotransposition of long interspersed nuclear element-1 (L1), a widespread mobile element in the human genome, is poorly understood in normal cells. Here we explored the whole-genome sequences of 899 single-cell clones established from three different cell types collected from 28 individuals.

Clonal dynamics in early human embryogenesis inferred from somatic mutation.

Cellular dynamics and fate decision in early human embryogenesis remain largely unknown owing to the challenges of performing studies in human embryos. Here, we explored whole-genomes of 334 single-cell colonies and targeted deep sequences of 379 bulk tissues obtained from various anatomical locations of seven recently deceased adult human donors. Using somatic mutations as an intrinsic barcode, we reconstructed early cellular phylogenies that demonstrate (1) an endogenous mutational rate that is higher in the first cell division but decreases to approximately one per cell per cell division later in life; (2) universal unequal contribution of early cells to embryo proper, resulting from early cellular bottlenecks that stochastically set aside epiblast cells within the embryo; (3) examples of varying degrees of early clonal imbalances between tissues on the left and right sides of the body, different germ layers and specific anatomical parts and organs; (4) emergence of a few ancestral cells that will substantially contribute to adult cell pools in blood and liver; and (5) presence of mitochondrial DNA heteroplasmy in the fertilized egg.

SiNG-PCRseq: Accurate inter-sequence quantification achieved by spiking-in a neighbor genome for competitive PCR amplicon sequencing.

Despite the recent technological advances in DNA quantitation by sequencing, accurate delineation of the quantitative relationship among different DNA sequences is yet to be elaborated due to difficulties in correcting the sequence-specific quantitation biases. We here developed a novel DNA quantitation method via spiking-in a neighbor genome for competitive PCR amplicon sequencing (SiNG-PCRseq). This method utilizes genome-wide chemically equivalent but easily discriminable homologous sequences with a known copy arrangement in the neighbor genome.

The obesity-risk variant of FTO is inversely related with the So-Eum constitutional type: genome-wide association and replication analyses.

Background: Body constitutional types described in the traditional Korean medicine system, Sasang constitutional medicine, are heritable, as has been revealed by twin and family studies. Thus, individuals with the same constitution type usually have similar pathophysiological and psychological traits. In several recent genome-wide association (GWA) analyses performed to identify constitution-associated variants, the association signals were not replicated due to small sample size and dissimilar, non-objective methods for classification of the constitutional types.

Identification of cis-regulatory variations in the IL6R gene through the inheritance assessment of allelic transcription.

Background: The level of circulating interleukin-6 receptor in human blood varies depending on the genetic and/or physiological causes, and has been implicated in the development of chronic inflammatory diseases.

Method: The cis-regulatory effects of genetic variations on the transcription of interleukin-6 receptor gene, IL6R,were studied by assessing allelic transcriptions in the immortalized lymphocytes derived from unrelated and familial samples.

Results: The assays for allelic transcription in the cells from unrelated subjects demonstrated an extensive and variable range of allelic transcriptional imbalances, suggesting an operation of multiple cis-regulations with varying degrees on the locus.

Association of apolipoprotein A5 gene -1131T>C polymorphism with the risk of metabolic syndrome in Korean subjects.

We assessed the associations between the APOA5  -1131T>C polymorphism and lipid parameters and other risk factors of the metabolic syndrome in Korean subjects. A total of 2,901 participants from 20 oriental medical hospitals in Korea were enrolled between 2006 and 2011. According to the modified National Cholesterol Education Program Adult Treatment Panel III definitions, subjects were classified into the metabolic syndrome group and control group.