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ABSTRACT: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication, absence or delay in language development, and stereotyped or repetitive behaviors. Genetic studies show that neurexin-neuroligin (NRXN-NLGN) pathway genes contribute susceptibility to ASD, which include cell adhesion molecules , and scaffolding proteins and . Neuroligin proteins play an important role in synaptic function and trans-synaptic signaling by interacting with presynaptic neurexins. Shank proteins are scaffolding molecules of excitatory synapses, which function as central organizers of the postsynaptic density. Sequence level mutations and structural variations in these genes have been identified in ASD cases, while few studies were performed in Chinese population. In this study, we examined the copy numbers of four genes and in 285 ASD cases using multiplex fluorescence competitive polymerase chain reaction (PCR). We also screened the regulatory region including the promoter region and 5'/3' untranslated regions (UTR) and the entire coding region of in a cohort of 285 ASD patients and 384 controls by direct sequencing of genomic DNA using the Sanger method. DNA copy number calculation in four genes showed no deletion or duplication in our cases. No missense mutations in were identified in our cohort. Association analysis of 6 common SNPs in did not find significant difference between ASD cases and controls. These findings showed that these genes may not be major disease genes in Chinese ASD cases.
PLoS ONE 01/2013; 8(2):e56639. · 4.09 Impact Factor
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ABSTRACT: The chemokine receptors and ligand CCR5, CXCR4 and SDF-1 play important roles in the entry of HIV-1 into host cells. Genetic polymorphisms such as CCR5-Δ32 and SDF-1 3'A have been reported to be associated with HIV-1 susceptibility and the progression of AIDS. Considering the remarkable difference in CCR5-Δ32 allele frequency among worldwide populations, we aimed to survey the genetic variations in CCR5, CXCR4 and SDF-1 in different Chinese populations. The open reading frames and regulatory regions of CCR5, CXCR4 and SDF-1 were sequenced in 141 Chinese individuals from three ethnic groups: Han, Mongol and Uyghur. Ninety-six variants were identified, 41 of which were newly identified (NI) in Chinese populations. A novel non-synonymous variant c.459 C>T (Trp153Cys) within CCR5 was identified in one Han individual. Of NI variants, 11 were common polymorphisms with a minor allele frequency (MAF) >5%. The polymorphism CCR5-Δ32 was found in three Uyghur individuals but was absent in Han and Mongol groups. The linkage disequilibrium (LD) analysis of CCR5 and SDF-1 and frequency of CCR5 haplotypes showed considerable divergence among three ethnic groups. Our results show the great genetic heterogeneity within CCR5, CXCR4 and SDF-1 in Chinese ethnic populations.
Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases 07/2012; 12(5):1072-8. · 3.22 Impact Factor
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Xiaohong Gong,
Yu-Wu Jiang,
Xin Zhang,
Yu An,
Jun Zhang,
Ye Wu,
Jingmin Wang,
Yangfei Sun,
Yanyan Liu,
Xuewu Gao,
Yiping Shen,
Xiru Wu,
Zilong Qiu,
Li Jin,
Bai-Lin Wu,
Hongyan Wang
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ABSTRACT: Intellectual disability (ID) is a heterogeneous disorder caused by chromosomal abnormalities, monogenic factors and environmental factors. 22q13 deletion syndrome is a genetic disorder characterized by severe ID. Although the frequency of 22q13 deletions in ID is unclear, it is believed to be largely underestimated. To address this issue, we used Affymetrix Human SNP 6.0 array to detect the 22q13 deletions in 234 Chinese unexplained ID patients and 103 controls. After the Quality Control (QC) test of raw data, 22q13 deletions were found in four out of 230 cases (1.7%), while absent in parents of the cases and 101 controls. A review of genome-wide microarray studies in ID was performed and the frequency of 22q13 deletions from the literatures was 0.24%, much lower than our report. The overlapping region shared by all 4 cases encompasses the gene SHANK3. A heterozygous de novo nonsense mutation Y1015X of SHANK3 was identified in one ID patient. Cortical neurons were prepared from embryonic mice and were transfected with a control plasmid, shank3 wild-type (WT) or mutant plasmids. Overexpression of the Y1015 mutant in neurons significantly affected neurite outgrowth compared with shank3 WT. These findings suggest that 22q13 deletions may be a more frequent cause for Chinese ID patients than previously thought, and the SHANK3 gene is involved in the neurite development.
PLoS ONE 01/2012; 7(4):e34739. · 4.09 Impact Factor
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Shuhua Xu,
Xianyong Yin,
Shilin Li,
Wenfei Jin,
Haiyi Lou,
Ling Yang, Xiaohong Gong,
Hongyan Wang,
Yiping Shen,
Xuedong Pan, [......],
Yu An,
Jiucun Wang,
Jingze Tan,
Ji Qian,
Xiaoli Chen,
Xin Zhang,
Yangfei Sun,
Xuejun Zhang,
Bailin Wu,
Li Jin
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ABSTRACT: To date, most genome-wide association studies (GWAS) and studies of fine-scale population structure have been conducted primarily on Europeans. Han Chinese, the largest ethnic group in the world, composing 20% of the entire global human population, is largely underrepresented in such studies. A well-recognized challenge is the fact that population structure can cause spurious associations in GWAS. In this study, we examined population substructures in a diverse set of over 1700 Han Chinese samples collected from 26 regions across China, each genotyped at approximately 160K single-nucleotide polymorphisms (SNPs). Our results showed that the Han Chinese population is intricately substructured, with the main observed clusters corresponding roughly to northern Han, central Han, and southern Han. However, simulated case-control studies showed that genetic differentiation among these clusters, although very small (F(ST) = 0.0002 approximately 0.0009), is sufficient to lead to an inflated rate of false-positive results even when the sample size is moderate. The top two SNPs with the greatest frequency differences between the northern Han and southern Han clusters (F(ST) > 0.06) were found in the FADS2 gene, which associates with the fatty acid composition in phospholipids, and in the HLA complex P5 gene (HCP5), which associates with HIV infection, psoriasis, and psoriatic arthritis. Ingenuity Pathway Analysis (IPA) showed that most differentiated genes among clusters are involved in cardiac arteriopathy (p < 10(-101)). These signals indicating significant differences among Han Chinese subpopulations should be carefully explained in case they are also detected in association studies, especially when sample sources are diverse.
The American Journal of Human Genetics 11/2009; 85(6):762-74. · 10.60 Impact Factor
