Paternal heritage of the Han Chinese in Henan province (Central China): high diversity and evidence of in situ Neolithic expansions.

Background: Due to their long history, complex admixture processes and large population sizes, more research is required to explore the fine genetic structure of Han populations from different geographic locations of China.Aim: To characterise the paternal genetic structure of the Han Chinese in Henan province, which was once the central living region of the ancient Huaxia population, the precursors of the Han Chinese.Subjects and methods: We sequenced Y chromosomes of 60 males from Zhengzhou, Henan Province, and reconstructed a phylogenetic tree for these samples with age estimation.Results: We observed high diversity of paternal lineages in our collection. We found that the in situ Neolithic expansion of the "Major lineages" contributed to a large portion of the paternal gene pool of the Han population in Henan Province. We also detected a large number of "Minor lineages" that diverged in the Palaeolithic Age.Conclusion: We suggest that the high genetic diversity in the paternal gene pool of modern Han populations is mainly attributed to the reservation of a larger number of lineages that diverged in the Palaeolithic Age, while the recent expansion of limited lineages contributed to the majority of the gene pool of modern Han populations. We propose that such a structure is a basal characteristic for the genetic structure of modern Han populations.

Curcumin Exerts Effects on the Pathophysiology of Alzheimer's Disease by Regulating PI(3,5)P2 and Transient Receptor Potential Mucolipin-1 Expression.

BACKGROUND: To validate our speculation that curcumin may ameliorate Alzheimer's disease (AD) pathogenesis by regulating PI(3,5)P2 and transient receptor potential mucolipin-1 (TRPML1) expression levels. METHODS: We developed an animal model presenting AD by APP/PS1 transgenes. The mouse clonal hippocampal neuronal cell line HT-22 was treated with amyloid-ß1-42 (Aß1-42). Curcumin was administrated both in vivo and in vitro. MTS assay was used to detect cell viability, and the lysosomal [Ca2+] ion concentration was detected. The number of autophagosomes was detected by the transmission electron microscopic examination. Illumina RNA-seq was used to analyze the different expression patterns between Aß1-42-treated cells without and with curcumin treatment. The protein level was analyzed by the Western blotting analysis. PI(3,5)P2 or TRPML1 was knocked down in HT-22 cells or in APP/PS1 transgenic mice. Morris water maze and recognition task were performed to trace the cognitive ability. RESULTS: Curcumin increased cell viability, decreased the number of autophagosomes, and increased lysosomal Ca2+ levels in Aß1-42-treated HT-22 cells. Sequencing analysis identified TRPLML1 as the most significantly upregulated gene after curcumin treatment. Western blotting results also showed that TRPML1 was upregulated and mTOR/S6K signaling pathway was activated and markers of the autophagy-lysosomal system were downregulated after curcumin use in Aß1-42-treated HT-22 cells. Knockdown of PI (3,5)P2 or TRPML1 increased the protein levels of markers of the autophagy-lysosomal system after curcumin use in Aß1-42-treated HT-22 cells, inhibited mTOR/S6K signaling pathway, increased the protein levels of markers of the autophagy-lysosomal system after curcumin use in APP/PS1 mice. Besides, knockdown of PI(3,5)P2 or TRPML1 reversed the protective role of curcumin on memory and recognition impairments in mice with APP/PS1 transgenes. CONCLUSION: To some extent, it suggested that the effects of curcumin on AD pathogenesis were, at least partially, associated with PI(3,5)P2 and TRPML1 expression levels.

[A study on paternity testing with 96 autosomal SNPs].

OBJECTIVE: To explore the feasibility of applying autosomal single nucleotide polymorphisms (SNPs) on parentage testing. METHODS: All SNP genotyping results of HapMap (r27) were downloaded from the website. With self-made computer programs, SNPs were extracted when their minor allele frequency (MAF) were ≥ 0.30 among all of the 11 HapMap populations. Ninety-six SNPs were chosen and integrated into the Illumina Goldengate bead arrays on the condition that no linkage disequilibrium was found between them. Three father-child-mother trios (9 samples in total) were tested with the arrays. Cumulative paternity index (CPI) was then calculated and compared with genotyping results using 15 short tandem repeats (STRs)(Identifiler(TM)). RESULTS: Family 1 was found to have nine SNPs or seven STRs that did not conform to the Mendelian laws, Family 2 had 13 such SNPs or seven STRs, and Family 3 only had one such SNP but no STR. For Family 3, when all of the 96 SNPs were used in combine, the CPI was 1207, which had contrasted with the CPI by the 15 STRs, i.e., 355 869. CONCLUSION: When applied to paternity testing, the paternity exclusion (PE) value for a SNP is usually less than 1/3 of that of a STR. The proportion of SNPs not comforming to the Mendelian laws for the tested SNPs may not be as high as that of inconsistent STRs over all tested STRs. Because of the low mutation rate of a SNP, the CPI will be greatly reduced even if one SNP did not conform to the Mendelian laws. Therefore, highly accurate testing methods are required to reduce artificial errors when applying SNPs for paternity testing.

Functional polymorphism in exon 5 and variant haplotype of the interleukin-1 receptor-associated kinase 1 gene are associated with susceptibility to and severity of sepsis in the Chinese population.

BACKGROUND: The interleukin-1 (IL-1) receptor-associated kinase 1 (IRAK1) is believed to play an important role in the pathogenesis of sepsis. Recent studies have suggested that the IRAK1 functional genetic variant could affect the severity of sepsis in Caucasians. In this report, we have investigated whether polymorphisms at the IRAK1 gene are associated with the susceptibility to and severity of sepsis among the Chinese population. METHODS: Haplotype-tagging single nucleotide polymorphisms (htSNPs) were selected from the HapMap database. They were genotyped in 255 patients with sepsis and 260 control subjects by PCR/restriction fragment length polymorphism (RFLP) analysis. The association between the selected htSNPs and the susceptibility to and severity of sepsis were estimated by Logistic regression with adjustments for age, sex, smoking, drinking, chronic disease status, Acute Physiology and Chronic Health Evaluation (APACHE) II score and primary diseases. RESULTS: rs1059702 was selected to represent the six linked htSNPs for IRAK1. Genotype frequencies of the htSNPs were in Hardy-Weinberg equilibrium for females, as were allele frequencies for both sex groups. Associations were observed in females between the htSNPs C/C genotype and increased susceptibility to sepsis (odds ratio (OR), 5.46; 95% confidence interval (CI), 1.12 - 26.67; P = 0.018), and such associations were also observed between the IRAK1 variant haplotype (CC/C-allele) and increased susceptibility to sepsis (OR, 1.68; 95% CI, 1.05 - 2.70; P = 0.031) when compared with the T/T + T/C genotype and the wild-type haplotype (TC + TT/T-allele). In the multiple organ dysfunction syndrome (MODS) subgroup, the variant haplotype was also associated with increased severity of sepsis (OR, 2.37; 95% CI, 1.13 - 4.94; P = 0.02) when compared with the wild haplotype. This association was not significant in male patients. CONCLUSIONS: The functional polymorphism in exon 5 and the variant haplotype of IRAK1 gene mediate susceptibility to and severity of sepsis. IRAK1 might be a genetic risk factor for the occurrence and development of sepsis in the Chinese population.

Population genetic data of 15 STR loci in Han population of Henan province (central China).

Allele frequencies of the 15 STR loci were determined in 208 unrelated individuals from Han population living in Henan, China (central China). All loci except D5S818 were found no deviation from Hardy-Weinberg equilibrium. The combined power of discrimination (PD) and the combined chance of exclusion (CE) for the 15 studied loci were >0.9999999 and 0.999996119, respectively. Our data were statistically compared with the previously reported data from other Chinese population groups, and significant difference was found between central Han Chinese (n=208) and eastern Chinese (n=100) at vWA, or between central Han Chinese (n=208) and southeast Chinese (n=122) at D13S317.

[A PCR-RFLP analysis to HLA-B gene among Chinese northern Han populations].

OBJECTIVE: To set up the method for analyzing HLA-B gene polymorphism with PCR-RFLP, and to gain population data among northern Chinese Hans of HLA-B's restricted fragments after NlaIII digestion, and to achieve application in forensic medicine practice. METHODS: Sample DNA was extracted by the phenol/chloroform extraction method, 943 bp-long fragments containing HLA-B exon 2 and 3 were got by PCR. The endonuclease NlaIII was applied to cut the PCR products into polymorphic fragments shorter than 943bp, then PAGE and silver staining were used to detect the digestion results, finally the digestion sites were assured by DNA sequencing. RESULTS: Along 943bp-long PCR products, 14 length-different fragments, 20 kinds of fragment combinations were got and 6 cutting site were observed after NlaIII digestion. CONCLUSION: HLA-B gene was highly polymorphic among Chinese northern Hans. Even with only one endonuclease, 14 restricted fragments were got and the PIC was great. Such a HLA-B PCR-RFLP analysis will have values in forensic medicine applications.

Progress in searching for susceptibility gene for inflammatory bowel disease by positional cloning.

Inflammatory bowel disease (IBD) includes two clinical subtypes: Crohn disease (CD) and ulcerative colitis (UC). The general prevalence is about 1.0-2.0 % in Western countries. It is predominantly regarded as a multifactorial disorder involving environmental factors and polygenic defects. The view was confirmed by a lot of evidences from clinical attributions and animal models, especially from epidemiological investigations. So the etiological study of IBD has been focused on searching for susceptibility genes by positional cloning, which consists of two steps: linkage analysis and association analysis. Linkage analysis has been an important method of searching for susceptibility genes to polygenic diseases as well as single-gene disorders. IBD, as a polygenic disease, has been widely investigated by linkage analysis for susceptibility gene since 1996. The paper reviewed 38 articles, which covered almost all original researches in relation to IBD and linkage analysis. So far, several loci, such as 16q, 12q, 6p and 3p, have been identified by the studies. The most striking is 16q12 (IBD1), which linked only with CD not UC in the majority of studies. Association analysis, as one essential step for positional cloning, is usually carried out by genotyping candidate genes selected by means of linkage analysis or other methods, for figuring out the frequencies of alleles and comparing the frequencies between IBD group and healthy control group to identify the specific allele. It has been established that IBD is implicated in immune disorder. So the studies were centered on the genes of NOD2/CARD15, HLA-II, cytokine, cytokine receptor and adhesion molecule. This paper reviewed 14 original articles on association between NOD2 and IBD that have been published since 2001. All results, with the exception of one report from a Japanese group, provide evidences that the three kinds of variants of NOD2 are susceptibility factors for IBD. This article also comprehensively analyzed 18 original researches of HLA gene polymorphism in IBD. We found extensive discrepancy among the conclusions and a novel hypothesis was put forward to explain the discordance. Most studies published recently on association between IBD and cytokine gene polymorphism were reviewed.