姓名：王嵬

出生年月： 1960 年 5 月 28 日

国籍：中国（澳大利亚永久居民）



地址：

1)

首都医科大学公共卫生与家庭医学学院

北京 邮编 100054

北京右安门外外西头条10号

Tel/fax: ＋ 86 － 10 － 83911504

E-mail: wei6014@gscas.ac.cn



2)

中国科学院研究生院生物系

北京 邮编 100039

北京玉泉路 19 甲

Tel/fax: ＋ 86 － 10 － 88256373

E-mail: wei6014@gscas.ac.cn



3)

Centre for Human Genetics,

Edith Cowan University,

Joondalup campus,

WA 6027

Australia

Tel: +61-8-6304-5467

Fax:+61-8-6304-5851

E-mail:w.wang@ecu.edu.au



教育经历：



1978-1983 ： 中国医科大学就读，获医学学士学位

1983-1986 ： 中国医科大学就读，获医学硕士学位

1986-1987 ： 中国医科大学第一附属医院任住院医生

1987-1988 : 英国伦敦大学皇家医学院访问学者

1988-1989 ： 瑞士苏黎士大学访问学者

1992-1993 ： 日本学术振兴学会 高级 客座研究员

1992-1997 ： 日本大分医科大学就读，获医学博士学位

1997-2000: 澳大利亚 Edith Cowan 大学 遗传学 中心博士后



工作经历：



1987-1990 ： 中国医科大学法医学系助教

1990-1993 ： 中国医科大学法医学系讲师

1993-1997: 日本大分医科大学医学部文部教官（日本国家公务员）

1997-2003: 澳大利亚 Edith Cowan 大学生物学系讲师

2001 至今 : 中国华中科技大学同济医学院教授

2003-2004: 深圳北京大学香港科技大学医学中心科研教育部副部长

2003 至今 : 澳大利亚 Edith Cowan 大学生物学系兼职教授

2004 至今 : 中国科学院“百人计划”海外特聘教授

2004 至今 : 中国科学院研究生院生物系副主任





学术成就



1983 年以来，长期从事人类遗传学及 分子 遗传流行病学领域的研究及教学工作，曾获多项课题研究基金，其中包括“中国国家自然科学基金”、“日本文部省科学基金” , “ 日本学术振兴学会 基金”、“法国巴斯德 (Pasteur) 研究所研究基金”、英国“ The Wellcome Trust ”科研基金和“澳大利亚国家科技部研究基金”，为其中四项课题的第一申请人及项目负责人。



迄今，已在国外发表学术论文 50 余篇，其中 40 余篇收录于 SCI 收录高影响因子杂志。参与著书一册，由英国著名出版社 Taylor & Francis 发行。多次在美国、英国、澳大利亚、日本、印度及中国举行的国际学术会议上作论文报告，重点发言。 2004 年在深圳主办了国际学术会 “ Community Genetics in Asia ” .



另外，还担任了国际 杂志 《 Annals of Human Biology 》、《 Genomics, Proteomics & Bioinformatics 》及 中国妇产科学会杂志《 首都医科大学学报》 ， 《中国妇产科临床》 的编委，并为《 American Journal of Medical Genetics 》 , 《 Human Biology 》 , 《 Journal of Human Hypertension 》等杂志的特约审稿人。



现任中国科学院研究生院 学术 委员会委员、中国科学院教材编撰委员会委员、深圳北京大学香港科技大学医学中心 学位 委员会委员、中国科学院 及 首都医科大学博士生导师、美国 Gerson Lehrman Group"s Council 的咨询顾问。





专利：

心脏急救起搏植入装置（专利申请号： 03211977.1 ）。



语言特长：

母语为中文，同时精通英文和日文的听、说、读、写。



技术特长：

从事人类医学遗传学 , 分子 遗传流行病学 和法医学工作。特别是在近亲结婚、遗传病和亲子鉴定、生物信息学方面作了大量研究。擅长 PCR 、微卫星分析技术、 DNA 序列测定、基因克隆、基因文库筛查、 RFLP 、 SSCP 、 DNA, RNA 和蛋白印记、免疫分析、电泳分析、等电聚焦、同工酶分析和血型分析等技术。



杂志编委及特约审稿人：

《 Annals of Human Biology 》

《 American Journal of Medical Genetics 》

《 Genomics, Proteomics & Bioinformatics 》

《 Human Biology 》

《 Journal of Human Hypertension 》

《 首都医科大学学报》

《 中国妇产科临床》



研究生培养：

硕士生、博士生导师



发表论文 ：





McElreavey K, Wang W and. Bittles A.H (2005): Report: 1 st Asian Genomic and Community Genetics Workshop. Community Genetics, in press

Yuan J, Yun H, Lan W, Wang W, Sullivan S G, Jia S, and Bittles AH （ 2005 ） A climatological investigation of the SARS-CoV outbreak in Beijing, PR China . American Journal of Infection Control, in press.

Jia S.W., Wang W., LiuY. and Wu Z.M. (2005) Neuroimaging Studies of Brain Corpus Striatum Changes among Heroin Dependent Patients Treated with Herbal Medicine, U"finer TM Capsule Addiction Biology , in press.

Li R, Cai Z, Zhong, Zhuang G and Wang W (2005): Normal ultrasound-guided embryo transfer improves clinical pregnancy rates after in –vitro fertilization: experiences from 330 cases of clinical investigations. Journal of the Assisted Reproductive Medicine , in press.

Shao C, Xiong W and Wang W (2005) Characterization of rare D Va (Hus) allele at RH loci. Journal of Human Genetics. In press.

Wang, W., Wise, C., Baric, T., Black, M.L. and Bittles, A.H. (2003) The origins and genetic structure of three co-resident Chinese Muslim Populations: the Salar, Bo"an and Dongxiang Human Genetics . 113:244-252.

Wang, W., Jia HL, Wang, Q., Cai Z.M., Wei, L.H., Wang, D.B., Bittles, A.H. (2003) STR polymorphisms of ‘forensic loci" in northern Han Chinese population. Journal of Human Genetics. 48: 337-341.

Wise, C., Paris, M., Morar, B., Wang, W., Kalaydjieva, L. and Bittles A.H. (2003) Single nucleotide polymorphism analysis using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry: Optimization and applications in human genetics. Rapid Communications in Mass Spectrometry. 17: 1195-1202.

Tian, H., Wang , W., Teng, Y., Wang, H., Hu, X., Chen, Y. and Bittles A.H. (2003) Autosomal dominant retinitis pigmentosa in a 5-generation pedigree in pr china. Eye. 17: 1036-1039.

Huang, Y.F., Wang, W., Han, J.Y., Zhang, S.T. Liu, C.J., Hu, Q.G., Xiong, P., Wu, X.W., Hamvas, R., Wood, N., Gong , F.L. and Bittles A.H. (2003) Association of mannose-binding lectin (MBL) LX haplotype with Chinese SLE patients. European Journal of Immunogenetics. 30: 121-124.

Wang, W., Qian, C. and Bittles, A.H. (2002) Consanguineous marriage in PR China: a study in rural Man (Manchu) communities. Annals of Human Biology. 29, 685-690.

Black, M., Wang, W. and Bittles, A. H. (2001) A genome-based study of the Muslim Hui community and the Han population of Liaoning Province , PR China. Human Biology . 73 , 801-813 .

Kulski, J.K, Martinez , P., Shiina, H., Jacobsen, N., Wang, W ., Naruse, T., Inoko, H., and Dawkins, R.L. (2001) The detection of a strong but imperfect association between HLA-A2 and the newly identified domorphic Alu insertion near HLA-G. Journal of Molecular Evolution, 53 , 114-123 .

Wang, W and Bittles, A.H. (2001) Imperfect units of an extended microsatellite structure involving single nucleotide changes. Electrophoresis . 22 , 1095-1097.

Bittles, A. H, Wang, W. Kumm, J, Di Grandi, S. Savithri, H.S., and. Appaji Rao, N. (2001) A genome-based investigation of consanguineous marriage in south India. American Journal of Physical Anthropology. 32 Supp. 40-41 .

Zhivotovsky, L.A. , Suhaib, A., Wang, W. and Bittles, A. H. (2001) Deep genetic differentiation among co-resident endogamous communities and its forensic DNA implications. Forensic Science International. 119, 269-272 .

Ahmed, S., Wang, W., Sullivan, S., and Bittles, A.H (2000) The influence of long-term inbreeding on human genome structure in three endogamous Pakistan communities. DNA Polymorphism 8 , 145-149.

Bittles, A.H., Kumm, J, Wang, W., Di Grandi, S. Savithri, H.S., and. Appaji Rao, N., (2000) Calculating a genomic estimate of consanguinity. Journal of Medical Genetics. 37 Supp., 70 .

Baric, T., Wang, W. and Bittles, A..H. (2000) Genetic diversity among the Salar, Bo"an, and Dongxiang Muslim populations in the Peoples Republic of China . Journal of Medical Genetics. 37 Supp., 69 .

Baric, T., Worsley, P., Wang, W. , Kalaydjieva, L., and Bittles, A.H. (2000) MALDI-TOF mass spectrometry and single nucleotide polymorphism analysis in human populations. Journal of Medical Genetics. 37 Supp., 71 .

Wang, W. and Bittles, A.H. (2000) Allelic homoplasy of STR due to variable allelic flanking sequences: SNPs in STR. American Journal of Human Genetics. 67 Supp., 220

Savithri, H.S., Venkatesha Murthy, H.S., Baskaran,G.,Appaji Rao, N., Kool, D., Edkins,E., Wang. W. and Bittles, A.H. (2000) Predictive testing for familial adenomatous polyposis in a rural South Indian community. Clinical Genetics 8 , 57-60.

Savithri,H.S., Venkatesha Murthy,H.S., Baskaran, G. and Appaji Rao, N. Wang , W . and Bittles, A.H. (2000). Mutation detection and predictive testing for familial adenomatous polyposis in a rural South Indian community. DNA Polymorphism 8, 63-65.

Wang, W. , Black, M., Qian, C., Jia, HL. and Bittles, A. H. (2000) Autosomal and Y-chromosome allele profiles in co-resident Han and Hui communities in northeast China . DNA Polymorphism 8 , 167-171.

Wang, W ., Sullivan, S., Ahmed, S., Chandler , D. Zhivotovsky, L.A. and Bittles, A.H. (2000) A genome-based study of consanguinity in three endogamous Pakistan communities. Annals of Human Genetics 64 , 41-49 .

Ahmed, S ., Wang, W., Sullivan, S., Chandler , D. and Bittles, A.H. (1999) Microsatellite analysis of autosomal and Y-chromosome variation in three consanguineous communities in Pakistan . Annals of Human Biology 26 , 394-395.

Bittles, A.H ., Wang, W ., Nan, L., Shuzhuo, L., Feldman, M.W. (1999) Effects of the 1981 marriage Act of China on the prevalence and patterns of marital union. Annals of Human Biology 26 , 397-398.

Bittles, A.H., Wang, W ., Di Grandi, S., Cahill,J., Savithri,H.S., Venkatesha Murthy,H.S., Baskaran, G. and Appaji Rao, N. (1999) A DNA-based analysis of long-term human inbreeding. Journal of Medical Genetics 36 supp., 31.

Savithri, H.S., Venkatesha Murthy, H.S., Appaji Rao, N., Cahill, J., Wang, W. and Bittles, A.H. (1998) Genomic analysis of long-term consanguinity in a rural south Indian community. Annals of Human Biology 25 , 290-291.

Wang, W. , Okazaki ,K., Kishida, T., Fukuda, M. and Tamaki, Y. (1997) Subtyping of D20S85 STR alleles by single-strand conformation polymorphism (SSCP) analysis. Forensic Science International 86 , 187-192.

Wang, W ., Kishida, T., Fukuda, M. and Tamaki, Y. (1996) The Y-27H39 polymorphism in a Japanese population. International Journal of Legal Medicine 109 , 157-158.

Wang, W. , Liu., Y.,H and Jia, J.T. (1991) Modified method for showing Gc subtypes and the discovery of two new variants of Gc subtypes from Chinese. Journal of China Medical University 20 Supp., 29-32.

Qi, S. W., Jia, J. T. and Wang, W. (1991) Ultrasensitive Silver staining for the detection of protein genetic markers and its application to forensic practice (In Chinese). Chinese Journal of Forensic Medicine 6 , 123-125.

Qi, S. W., Jia, J. T. and Wang, W . (1990) Transferrin (Tf) phenotyping in Chinese Han and its detection in bloodstains (In Chinese). Chinese Journal of Forensic Medicine 5 , 97-99. In Chinese.

Qi, S. W., Jia, J. T. and Wang, W . (1989) Genetic Polymorphisms of: a -1-antitrypsin and transferrin, and their application to Forensics (In Chinese). Chinese Journal of Forensic Medicine 4 , 117-120.

Wang, W . and Jia, J.T. (1987) Phenotyping of phosphoglucomutase (PGM1) subtypes in Chinese, with special reference to new variant PGM1 China. Medicine Science and Law. 27, 280-283.





编著书目：

Bittles, A.H., Savithri, H.S., Venkatesha Murthy, H.S., Wang, W., Cahill, J., Bhaskaran, G. and Appaji Rao, N. (2001) Consanguineous marriage, a familiar story full of surprises. In Health and Ethnicity, eds. H. Macbeth and P. Shetty, Taylor and Francis, London. pp 68-78.





A SUMMARY OF PAST AND CURRENT RESEARCH



1. Genomic analysis of long-term inbreeding in a South Indian population

Major advances are underway in the application of genomic data to the analysis of population structure. This task has been undertaken in a South Indian population for which a community history, comprehensive pedigrees, and genetic marker data are available. A likelihood-based analysis of microsatellite markers was performed to provide information regarding identity-by-descent (IBD) across individuals and across the genome. Since the ancestry of an individual determines the pattern of IBD, the information thus derived can be applied as an indicator of biological history. A fast Forward/Reverse Baum algorithm was first used to calculate the complete data likelihood from 50 dinucleotide markers on chromosomes 13, 15, 17 and 18, and subsequent analysis gave probabilities of IBD across the genome. Maximum likelihood error rates calculated by the method were low (1-3%). IBD patterns from 10 unrelated sibs and 10 sibs of consanguineous unions (ranging from 1 st to 2 nd cousins) were then compared. Across the genome the number of changes in IBD state per centiMorgan was significantly lower in the offspring of consanguineous marriage (1/1000cM vs 3/1000cM), thus allowing the identification of consanguineous marriages from genomic data. Statistically significant correlations in IBD patterns were found across chromosomes 13 and 15, confirming previously recorded gametic associations. Computational analysis of genetic marker data thus provides a valuable insight into important non-genetic population characteristics traits, such as consanguinity. The power of these indicators can however be sensitive both to the number of markers and the area of the genome covered, and short regions may show marked deviations from the whole genome pattern.



2. A genome-based study of consanguinity in three co-resident endogamous Pakistan communities

In a study based on 173 individuals drawn from three endogamous, co-resident communities in the province of Punjab, the Awan, Khattar and Rajpoot, an analysis of ten autosomal single tandem repeats on chromosome 13 and 15 revealed distinctive genetic profiles in each community. A total of 99 different alleles were detected, with 28 alleles (28.3%) shared by all three communities. The mean private allele frequency was 7.7%. There was a reduction in heterozygosity and high average inbreeding effects ( Fis and/or Hs ), particularly in the Awan, indicating genetic isolation and a high cumulative level of autozygosity. Genotyping with eight Y-chromosome STRs resulted in the construction of six haplotypes, one each for the Awan and the Khattar but four for the Rajpoot, suggesting marked variation in the patterns of male founder effects in the history of each community. The lower than expected levels of homozygosity observed at a number of loci may be indicative of co-segregation of the STRs with nearby early development genes subject to selection.





3. Mutation detection and predictive testing for familial adenomatous polyposis in a rural South Indian community



During the course of genome studies in a rural community in the South Indian state of Karnataka, DNA-based investigations and counselling for familial adenomatous polyposis (FAP ) were requested via the community physician. The propoaita died in 1940 and FAP had been clinically diagnosed in 2 of her 5 children, both deceased. DNA samples from 2 affected individuals in the third generation were screened for mutations in APC gene, and a frame-shift mutation was identified in exon 15 with a deletion at codon 1061. Predictive testing for the mutation was then organized on a voluntary basis. There were 11 positive tests, including confirmatory positive on 2 persons diagnosed by colonoscopy, and to date surgery has been successfully undertaken on 3 previously undiagnosed adults. The ongoing success of the study indicates that, with appropriate access to the facilities offered by collaborating centres, predictive testing is feasible for diseases such as FAP and could be of significant benefit to communities in economically less developed countries.





4 The origins and genetic structure of three co-resident Chinese Muslim Populations: the Salar, Bo"an and Dongxiang



A genome-based investigation of three endogamous Muslim populations, the Salar, Bo"an, and Dongxiang was conducted on 212 individuals (148 males, 64 females), co-resident in Jishisan County, a minority autonomous region located in the province of Gansu, PR China. The Salar are believed to be of Turkic origin whereas the Bo"an and Dongxiang both speak Mongolian. Ten bi-parental dinucleotide markers on chromosomes 13 and 15 were analyzed to estimate genetic diversity and the effects of endogamy. Four tri- and tetranucleotide Y-chromosome markers and 15 Y-chromosome unique event polymorphisms (UEPs) were examined to determine male-mediated gene flow. mtDNA (360 bp of hypervariable region I) was sequenced for female lineage analysis. Mean homozygosity levels were elevated at the autosomal loci in all three communities: the Salar (0.32), Bo"an (0.32), and Dongxiang (0.27), equivalent to inbreeding coefficients ( F is ) of 0.16; 0.12; 0.01 respectively. AMOVA analysis showed differing levels of disparity between the three populations, with inter-population variation of –2.2% for autosomal STRs, 1.2% for mtDNA and 29.4% for Y-chromosome STRs. Haplotype diversity for the Y-chromosome UEPs was high in the three populations: Salar (0.88), Bo"an (0.86), and Dongxiang (0.87). Besides sharing common ancient UEP markers, the results indicate diverse male origins but common maternal lineages for the three co-resident communities within a historical time-frame. These findings are best explained by past inter-marriage between the genetically diverse male founders of each community and Han Chinese females, with subsequent community endogamy.





5 Association of mannose-binding lectin (MBL) LX haplotype with Chinese SLE patients



Mannose-binding lectin (MBL) is an important complement-activating protein of the human immune system. Due to one of three structural gene mutations in exon one (variants B, C and D) and/or the presence of a low efficiency promoter polymorphism, MBL deficiency may be associated with increased susceptibility to infectious diseases and to autoimmune disorders, including systemic lupus erythematosus (SLE). Using a combined approach of heteroduplex generator and polymerase chain reaction, a systematic search for mutations in exon one and the promoter region of MBL gene was performed in a Chinese study population comprising 41 SLE patients and 111 healthy controls. Two alleles, a wild type allele A and a variant allele B (a previously reported mutation of GGC to GAC at codon 54) were identified in MBL exon one. The frequency of the B allele (0.15) was higher among the SLE patients than the healthy control samples (0.09), but the difference did not attain statistical significance ( p >0.05). However, for two polymorphisms at positions -550 and -221 in the promoter region the frequencies of the low-MBL producing haplotype (LX) in the patients (0.2073) were significantly higher than in the controls (0.0855) ( p = 0.003, RR = 2.79). Our results suggest that the LX haplotype represents a strong risk factor among Chinese SLE patients. Although of lesser importance, the MBL B allele also may be a risk component in the developing process of SLE in Chinese patients.





6. Autosomal dominant retinitis pigmentosa in a 5-generation pedigree in PR china



An extended 5-generation family has been investigated in which 32 of the 111 family members were diagnosed with retinitis pigmentosa (RP). The proband is a 58-year old male in whom night-blindness was first observed in early childhood, with almost loss of vision by 52 years of age. The symptoms observed in other family members included night-blindness, impaired vision and visual field loss. Dementia, digital abnormalities, deaf-mutism and mental retardation were variously diagnosed in a number of individuals with RP. The affected and unaffected family members were tested for mutations in a range of candidate genes. A novel mutation was identified in the rhodopsin gene at codon 52 of exon 1 (TTC-TAC) that resulted in a substitution of Tyr to Phe.





7. The preliminary criminal DNA program in PR China



A preliminary Chinese Criminal DNA Database has been constructed by the analysis of samples from 2,500 offenders in custody in Shanghai, southeast China. Thirteen autosomal tetranucleotide STRs widely used in forensic identification were selected for the DNA profiling, together with the X-Y homologous gene Amelogenin for sex determination . Only one of the 13 autosomal loci showed significant deviation from Hardy-Weinberg equilibrium in the individuals genotyped. The cumulative discrimination power and power of exclusion of the 13 loci were greater than 0.999999999 and 0.9999888 respectively , giving an average match probability of 5.5 x 10 -15 for the population. Allelic distributions at the vWA, TH01, D13S317 and D16S539 loci differed from African-Americans and U.S. Caucasians, and more detailed population data at these four loci may be needed to ensure their applicability for forensic purposes in Chinese populations. Previously unreported alleles were detected at several loci, some at relatively high frequencies, suggesting the need for their inclusion in the reference allelic ladder to meet the practical standard of forensic profiling in certain Chinese ethnic sub-populations. The preliminary DNA database provides base-line information applicable to the construction of a National Index System for criminal DNA profiling in PR China.



8.Cloning, expression and characterization of a novel human MDSRP from CD34 + stem/progenitor cells.



Myelodysplastic syndrome relative protein ( MDSRP ) gene was identified from human myelodysplastic syndrome (MDS) CD34 + cells. MDSRP contains 11 exons (3,535 bp; human chromosome 3q13.33) encoding a putative protein of 392 amino acids, with a highly conserved CAP10 domain, a hydrophobic signal peptide at its N-terminus, and an endoplasmic reticulum (ER) retention signal motif KTEL at the C-terminus. The homologs of MDSRP exist in different organisms from plants to animal kingdoms. Subcellular localization analysis showed that MDSRP is an ER–resident protein. MDSRP expressed in most human adult tissues at different intensities, with lengths of 3.5kb and 1.9kb. Transcript of MDSRP was not detectable in colon, thymus, and small intestine, but was abundant in liver, indicating that MDSRP may be of important physiological functions in liver, involving the regulation and development of hematopoietic stem/progenitor cells (HSPCs). MDSRP over-expressed U937 cells had higher growth rate than the cells without exogenic MDRSP protein expression, suggesting that MDSRP protein possess the ability of promote cell proliferation. MDSRP specifically blocked the TGF - β -induced expression of p15, but not p16. The study indicated that MDSRP might play an important role in leukaemia genesis.