Duen-Mei Wang

Chinese Academy of Sciences

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Jun Yu

Chinese Academy of Sciences

Yong‐Biao Zhang

Beihang University

Feng Zhang

Fudan University

Hongbin Lin

Southern Medical University

Songnian Hu

Chinese Academy of Sciences

Xin Li

Chinese Academy of Sciences

Xin Li

Nanjing Drum Tower Hospital

Joseph S. Lipsick

Stanford University

Zhenmin Zhao

Inner Mongolia Electric Power (China)

Ningbei Yin

Chinese Academy of Medical Sciences & Peking Union Medical College

Cooperative Institutions

Chinese Academy of Medical Sciences & Peking Union Medical College

Chinese Academy of Sciences

Capital Medical University

Peking Union Medical College Hospital

University of Chinese Academy of Sciences

Jilin University

Fudan University

Huazhong University of Science and Technology

Peking University

National Clinical Research Center for Digestive Diseases

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Genome-Wide Linkage Scan of a Pedigree with Familial Hypercholesterolemia Suggests Susceptibility Loci on Chromosomes 3q25-26 and 21q22

PLoS ONE (2011)

Xu Wang Xin Li Yong‐Biao Zhang Feng Zhang Liyuan Sun

Background Familial hypercholesterolemia (FH) is a heritable disorder that can increase the risk of premature coronary heart disease. Studies suggest there are substantial genetic heterogeneities for different populations. Here we tried to identify novel susceptibility loci for FH in a Chinese pedigree. Methodology/Principal Findings We performed a SNP-based genome-wide linkage scan with the Chinese FH pedigree. Two suggestive linkage loci not previously reported were identified on chromosomes 3q25.1-26.1 (NPL = 9.01, nominal P<0.00001, and simulated occurrence per genome scan = 1.08) and 21q22.3 (NPL = 8.95, nominal P<0.00001, and simulated occurrence per genome scan = 1.26). In the interaction analysis with a trimmed version of the pedigree, we obtained a significantly increased joint LOD score (2.70) compared with that obtained when assuming the two loci uncorrelated, suggesting that more than one locus was involved in this pedigree. Exon screening of two candidate genes ABCG1 and LSS from one of the suggestive region 21q22 didn't report any causative mutations. Conclusions/Significances These results confirm complex etiologies and suggest new genetic casual factors for the FH disorder. Further study of the two candidate regions is advocated.

Genome Scan

Genetic linkage

SNP

Candidate gene

10.1371/journal.pone.0024838

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Citations (14)

Genetic linkage analyses andCx50mutation detection in a large multiplex Chinese family with hereditary nuclear cataract

Ophthalmic Genetics (2010)

Wei He Xin Li Jiajing Chen Ling Xu Feng Zhang

Purpose: The aim of the study was to characterize the underlying mutation in a large multiplex Chinese family with hereditary nuclear cataract.Methods: A 6-generation Chinese family having hereditary nuclear cataract was recruited and clinically verified. Blood DNA samples were obtained from 53 available family members. Linkage analyses were performed on the known candidate regions for hereditary cataract with 36 polymorphic microsatellite markers. To identify mutations related to cataract, a direct sequencing approach was applied to a candidate gene residing in our linkage locus.Results: A linkage locus was identified with a maximum 2-point LOD score of 4.31 (recombination fraction = 0) at marker D1S498 and a maximum multipoint LOD score of 5.7 between markers D1S2344 and D1S498 on chromosome 1q21.1, where the candidate gene Cx50 is located. Direct sequencing of Cx50 showed a 139 G to A transition occurred in all affected family members. This transitional mutation resulted in a replacement of aspartic acid by asparagine at residue 47 (D47N) and led to a loss-of-function of the protein.Conclusions: The D47N mutation of Cx50 causes the hereditary nuclear cataract in this family in an autosomal dominant mode of inheritance with incomplete penetrance.

Genetic linkage

Penetrance

Candidate gene

Multiplex

10.3109/13816810.2010.535886

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On the Origin of Tibetans and Their Genetic Basis in Adapting High-Altitude Environments

PLoS ONE (2011)

Binbin Wang Yong‐Biao Zhang Feng Zhang Hongbin Lin Xumin Wang

Since their arrival in the Tibetan Plateau during the Neolithic Age, Tibetans have been well-adapted to extreme environmental conditions and possess genetic variation that reflect their living environment and migratory history. To investigate the origin of Tibetans and the genetic basis of adaptation in a rigorous environment, we genotyped 30 Tibetan individuals with more than one million SNP markers. Our findings suggested that Tibetans, together with the Yi people, were descendants of Tibeto-Burmans who diverged from ancient settlers of East Asia. The valleys of the Hengduan Mountain range may be a major migration route. We also identified a set of positively-selected genes that belong to functional classes of the embryonic, female gonad, and blood vessel developments, as well as response to hypoxia. Most of these genes were highly correlated with population-specific and beneficial phenotypes, such as high infant survival rate and the absence of chronic mountain sickness.

SNP

10.1371/journal.pone.0017002

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Citations (147)

Exploration of 16 candidate genes identifies the association of IDE with Alzheimer's disease in Han Chinese

Neurobiology of Aging (2010)

Fen Wang Chang Shu Longfei Jia Xiumei Zuo Yong‐Biao Zhang

SNP

Candidate gene

Genetic Association

10.1016/j.neurobiolaging.2010.08.004

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Citations (22)

A Preliminary Study of Copy Number Variation in Tibetans

PLoS ONE (2012)

Yong‐Biao Zhang Xin Li Feng Zhang Duen-Mei Wang Jun Yu

Genetic features of Tibetans have been broadly investigated, but the properties of copy number variation (CNV) have not been well examined. To get a preliminary view of CNV in Tibetans, we scanned 29 Tibetan genomes with the Illumina Human-1 M high-resolution genotyping microarray and identified 139 putative copy number variable regions (CNVRs), consisting of 70 deletions, 61 duplications, and 8 multi-allelic loci. Thirty-four of the 139 CNVRs showed differential allele frequencies versus other East-Asian populations, with P values <0.0001. These results indicated a distinct pattern of CNVR allele frequency distribution in Tibetans. The Tibetan CNVRs are enriched for genes in the disease class of human reproduction (such as genes from the DAZ, BPY2, CDY, and HLA-DQ and -DR gene clusters) and biological process categories of “response to DNA damage stimulus” and “DNA repair” (such as RAD51, RAD52, and MRE11A). These genes are related to the adaptive traits of high infant birth weight and darker skin tone of Tibetans, and may be attributed to recent local adaptation. Our results provide a different view of genetic diversity in Tibetans and new insights into their high-altitude adaptation.

10.1371/journal.pone.0041768

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Citations (25)

Members of the Caudal Family of Homeodomain Proteins Repress Transcription from the Human Apolipoprotein B Promoter in Intestinal Cells

Journal of Biological Chemistry (1996)

Soon-Youl Lee Brian P. Nagy Alan R. Brooks Duen-Mei Wang Bernhard Paulweber

Transcription

10.1074/jbc.271.2.707

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Citations (36)

Nucleotide polymorphism of the TNF gene cluster in six Chinese populations

Journal of Human Genetics (2010)

Yong‐Biao Zhang Feng Zhang Hongbin Lin Lei Shi Panpan Wang

International HapMap Project

Linkage Disequilibrium

Tag SNP

SNP

dbSNP

SNP genotyping

10.1038/jhg.2010.33

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Citations (5)

Genetic Heterogeneity of Oesophageal Cancer in High-Incidence Areas of Southern and Northern China

PLoS ONE (2010)

Guohong Zhang Min Su Duen-Mei Wang Songnian Hu Min Liu

Oesophageal cancer is one of the most common and deadliest cancers worldwide. Our previous population-based study reported a high prevalence of oesophageal cancer in Chaoshan, Guangdong Province, China. Ancestors of the Chaoshan population migrated from the Taihang Mountain region of north-central China, which is another high-incidence area for oesophageal cancer. The purpose of the present study was to obtain evidence of inherited susceptibility to oesophageal cancer in the Chaoshan population, with reference to the Taihang Mountain population, with the eventual goal of molecular identification of the disease genes.

10.1371/journal.pone.0009668

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Citations (61)

Mutational analysis of the transcriptional activation domains of v-Myb

Oncogene (2002)

Duen-Mei Wang Joseph S. Lipsick

MYB

Transcription

Heptad repeat

10.1038/sj.onc.1205236

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Citations (9)

Maternal Transmission Effect of a PDGF-C SNP on Nonsyndromic Cleft Lip with or without Palate from a Chinese Population

PLoS ONE (2012)

Di Wu Mei Wang Xingang Wang Ningbei Yin Tao Song

Cleft lip with or without palate (CL/P) is a common congenital anomaly with a high birth prevalence in China. Based on a previous linkage signal of nonsyndromic CL/P (NSCL/P) on the chromosomal region 4q31–q32 from the Chinese populations, we screened the 4q31–q32 region for susceptibility genes in 214 trios of Han Chinese. PDGF-C, an important developmental factor, resides in the region and has been implicated in NSCL/P. However, in our family-based association test (transmission disequilibrium test; TDT), we could not conclude an association between PDGF-C and NSCL/P as previously suggested. Instead, we found strong evidence for parent-of-origin effect at a PDGF-C SNP, rs17035464, by a likelihood ratio test (unadjusted p-value = 0.0018; Im = 2.46). The location of rs17035464 is 13 kb downstream of a previously reported, NSCL/P-associated SNP, rs28999109. Furthermore, a patient from our sample trios was observed with a maternal segmental uniparental isodisomy (UPD) in a region containing rs17035464. Our findings support the involvement of PDGF-C in the development of oral clefts; moreover, the UPD case report contributes to the collective knowledge of rare variants in the human genome.

Transmission disequilibrium test

Linkage Disequilibrium

SNP

Chinese population

Uniparental disomy

Genetic Association

Korean population

10.1371/journal.pone.0046477

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Citations (14)