The DNA methylome of human peripheral blood mononuclear cells.

DNA methylation plays an important role in biological processes in human health and disease. Recent technological advances allow unbiased whole-genome DNA methylation (methylome) analysis to be carried out on human cells. Using whole-genome bisulfite sequencing at 24.7-fold coverage (12.3-fold per strand), we report a comprehensive (92.62%) methylome and analysis of the unique sequences in human peripheral blood mononuclear cells (PBMC) from the same Asian individual whose genome was deciphered in the YH project. PBMC constitute an important source for clinical blood tests world-wide. We found that 68.4% of CpG sites and <0.2% of non-CpG sites were methylated, demonstrating that non-CpG cytosine methylation is minor in human PBMC. Analysis of the PBMC methylome revealed a rich epigenomic landscape for 20 distinct genomic features, including regulatory, protein-coding, non-coding, RNA-coding, and repeat sequences. Integration of our methylome data with the YH genome sequence enabled a first comprehensive assessment of allele-specific methylation (ASM) between the two haploid methylomes of any individual and allowed the identification of 599 haploid differentially methylated regions (hDMRs) covering 287 genes. Of these, 76 genes had hDMRs within 2 kb of their transcriptional start sites of which >80% displayed allele-specific expression (ASE). These data demonstrate that ASM is a recurrent phenomenon and is highly correlated with ASE in human PBMCs. Together with recently reported similar studies, our study provides a comprehensive resource for future epigenomic research and confirms new sequencing technology as a paradigm for large-scale epigenomics studies.

Origin and evolution of two Yugur sub-clans in Northwest China: a case study in paternal genetic landscape.

BACKGROUND: Yugur is an ethnic group that was officially identified by the Chinese Government in 1953. Within the population there are two sub-clans distinctly identified as the Eastern Yugur and Western Yugur, partly because they have different local languages. AIM: A parentage comparison was conducted between the two sub-clans to investigate their genetic relationship. SUBJECTS AND METHODS: Male subjects were chosen from the two clans to investigate their paternal genetic landscape through typing 14 single nucleotide polymorphisms (SNP) and 12 short tandem repeats (STR) of the Y chromosome. RESULTS: Significant differences were revealed between the sub-clans at the haplogroup level. Genetic divergence was also observed by analyses of multidimensional scaling (MDS) and principal components (PC). Genetically, the Eastern Yugur are closer to the Han Chinese and Mongolian people than the Western Yugur. The Uygur people, who share a common ancestor (ancient Huihu) with the Yugur, were genetically separate from both sub-clans of Yugur. Moreover, the constructed phylogenetic network for haplogroup O provided further evidence that the two Yugur sub-groups present an underlying genetic difference. CONCLUSION: Overall, the diffusion of Mongolians during the Mongol Period has affected the Eastern Yugur more than the Western Yugur. The genetic contribution of the Han people to the Eastern Yugur seems to be more pronounced than to the Western Yugur. Besides the two different contributions referred to above, small population size and genetic drift have resulted in the genetic differentiation of the current sub-clans of Yugur.

[Standardization for sharing and utilization of Chinese genetic resources].

National Infrastructure of Chinese Genetic Resources is a part of National Infrastructure of Natural Resources for Science and Technology. To strengthen and standardize the collection, integration, conservation, sharing and utilization of Chinese Genetic Resources, we have been carrying out the research on standardization of trimming, integration and sharing of Chinese Genetic Resources, according the advanced experiences abroad on that and abiding by the related laws and regulations. In the paper, National Infrastructure of Chinese Genetic Resources will be introduced on the standardization of integration, database construction and sharing of Chinese Genetic Resources.

Identification and characterization of a novel protein ISOC2 that interacts with p16INK4a.

p16(INK4a) is a multiple tumor suppressor, playing an important role in proliferation and tumorigenesis. To screen the p16(INK4a)-associated proteins, we performed a yeast two-hybrid assay and identified a novel protein isochorismatase domain containing 2 (ISOC2). ISOC2 conserves in different species, and encodes 205 and 210 amino acids in human and mouse, respectively. The expression of ISOC2 in mouse is universal but predominantly in uterus, stomach, and urinary tract system. Interaction between ISOC2 and p16(INK4a) was verified using in vitro pull-down assays and in vivo co-immunoprecipitation. Confocal microscopy studies using green and cyan fluorescent fusion proteins determined that ISOC2 co-localizes with p16(INK4a). Over-expressed ISOC2 is able to inhibit p16(INK4a) in dose-dependent manner. Our data indicated that ISOC2 is a novel functional protein, which is able to bind and co-localize with a tumor suppressor gene p16(INK4a). Over-expressed ISOC2 inhibits the expression of p16(INK4a), suggesting that this novel gene may play a role during the tumor development by interacting with p16(INK4a).

Testing the hypothesis of an ancient Roman soldier origin of the Liqian people in northwest China: a Y-chromosome perspective.

The Liqian people in north China are well known because of the controversial hypothesis of an ancient Roman mercenary origin. To test this hypothesis, 227 male individuals representing four Chinese populations were analyzed at 12 short tandem repeat (STR) loci and 12 single nucleotide polymorphisms (SNP). At the haplogroup levels, 77% Liqian Y chromosomes were restricted to East Asia. Principal component (PC) and multidimensional scaling (MDS) analysis suggests that the Liqians are closely related to Chinese populations, especially Han Chinese populations, whereas they greatly deviate from Central Asian and Western Eurasian populations. Further phylogenetic and admixture analysis confirmed that the Han Chinese contributed greatly to the Liqian gene pool. The Liqian and the Yugur people, regarded as kindred populations with common origins, present an underlying genetic difference in a median-joining network. Overall, a Roman mercenary origin could not be accepted as true according to paternal genetic variation, and the current Liqian population is more likely to be a subgroup of the Chinese majority Han.

Male demography in East Asia: a north-south contrast in human population expansion times.

The human population has increased greatly in size in the last 100,000 years, but the initial stimuli to growth, the times when expansion started, and their variation between different parts of the world are poorly understood. We have investigated male demography in East Asia, applying a Bayesian full-likelihood analysis to data from 988 men representing 27 populations from China, Mongolia, Korea, and Japan typed with 45 binary and 16 STR markers from the Y chromosome. According to our analysis, the northern populations examined all started to expand in number between 34 (18-68) and 22 (12-39) thousand years ago (KYA), before the last glacial maximum at 21-18 KYA, while the southern populations all started to expand between 18 (6-47) and 12 (1-45) KYA, but then grew faster. We suggest that the northern populations expanded earlier because they could exploit the abundant megafauna of the "Mammoth Steppe," while the southern populations could increase in number only when a warmer and more stable climate led to more plentiful plant resources such as tubers.

Recent spread of a Y-chromosomal lineage in northern China and Mongolia.

We have identified a Y-chromosomal lineage that is unusually frequent in northeastern China and Mongolia, in which a haplotype cluster defined by 15 Y short tandem repeats was carried by approximately 3.3% of the males sampled from East Asia. The most recent common ancestor of this lineage lived 590 +/- 340 years ago (mean +/- SD), and it was detected in Mongolians and six Chinese minority populations. We suggest that the lineage was spread by Qing Dynasty (1644-1912) nobility, who were a privileged elite sharing patrilineal descent from Giocangga (died 1582), the grandfather of Manchu leader Nurhaci, and whose documented members formed approximately 0.4% of the minority population by the end of the dynasty.

The genetic legacy of the Mongols.

We have identified a Y-chromosomal lineage with several unusual features. It was found in 16 populations throughout a large region of Asia, stretching from the Pacific to the Caspian Sea, and was present at high frequency: approximately 8% of the men in this region carry it, and it thus makes up approximately 0.5% of the world total. The pattern of variation within the lineage suggested that it originated in Mongolia approximately 1,000 years ago. Such a rapid spread cannot have occurred by chance; it must have been a result of selection. The lineage is carried by likely male-line descendants of Genghis Khan, and we therefore propose that it has spread by a novel form of social selection resulting from their behavior.