生物谷报道：通过一项基因谱相关分析研究鉴定了四种较新的鉴定基因――定位在9号染色体上的CDKN2A, CDKN2B基因，定位在3号染色体上的IGF2BP2基因以及CDKAL1基因――这项分析研究中，研究者详细调查了数千人群的染色体组来鉴别单核苷酸多态性（SNPs）。国际小组也证实了既往的发现：另六个基因遗传性变型――TCF7L2, SLC30A8, HHEX, PPARG, KCNJ11, 以及FTO――与糖尿病发展的风险性增高相关。
糖尿病一级亲属的糖尿病发生高风险性是一般人群的3.5倍，但迄今为止鉴别糖尿病的遗传危害因子的发现局限。进一步而言，需定义这种疾病的基因结构以及鉴别疾病发病机理中的生物学途径，1161例芬兰2型糖尿病患者和1174例芬兰正常葡萄糖耐量受试者参与芬兰－美国年青人非胰岛素依赖型糖尿病(FUSION) 和国家的FINRISK研究。通过SNPs关联分析后，研究者证实了染色体的三个新区域影响2型糖尿病的发生。此三个基因变异型定位于附近被认为调节胰岛素和那些在胰脏内促进胰岛素分泌增长的基因。除了鉴定出CDKN2A/CDKN2B，IGF2BP2, 和 CDKAL1外，研究者也检测11号染色体上既往不含有注释基因的区域。这样的结果在两个独立样本中被证实，第一个样本来自Wellcome病例对照协会，第二个为在DGI内瑞典和芬兰人的染色体组。既往鉴定的变异基因型-- TCF7L2, SLC30A8, HHEX, PPARG, KCNJ11和FTO—也被研究者证实，此结果有助于使得研究糖尿病发生的遗传性变型数目达到10. 研究人员接着检测了芬兰受试者的所有10项糖尿病相关遗传性变型的染色体组，并构建了一个logistic回归模型预测每个受试者的糖尿病风险性。通过这样，他们鉴定了存在遗传性变型的受试者发生糖尿病的风险达四倍之高，研究小组提到：通过这样他们看发现个体预防医学项目的潜在价值。研究者详细调查了数千人群的大样本染色体组来鉴别单核苷酸多态性（SNPs）。
《科学》刊物中2007年4月26号的作者Dr Laura Scott（密西根州Ann Arbor大学）在文章中写到：“研究的三组需要大量样本，我们能肯定糖尿病的新风险因子已经鉴定出来，每个基因的发现都有助于发病机制的阐明，所有的蛋白及相关途径都代表着糖尿病预防或治疗的药物潜在靶位点。
原文出处：
A Genome-Wide Association Study of Type 2 Diabetes in Finns Detects Multiple Susceptibility Variants
Laura J. Scott, Karen L. Mohlke, Lori L. Bonnycastle, Cristen J. Willer, Yun Li, William L. Duren, Michael R. Erdos, Heather M. Stringham, Peter S. Chines, Anne U. Jackson, Ludmila Prokunina-Olsson, Chia-Jen Ding, Amy J. Swift, Narisu Narisu, Tianle Hu, Randall Pruim, Rui Xiao, Xiao-Yi Li, Karen N. Conneely, Nancy L. Riebow, Andrew G. Sprau, Maurine Tong, Peggy P. White, Kurt N. Hetrick, Michael W. Barnhart, Craig W. Bark, Janet L. Goldstein, Lee Watkins, Fang Xiang, Jouko Saramies, Thomas A. Buchanan, Richard M. Watanabe, Timo T. Valle, Leena Kinnunen, Goncalo R. Abecasis, Elizabeth W. Pugh, Kimberly F. Doheny, Richard N. Bergman, Jaakko Tuomilehto, Francis S. Collins, and Michael Boehnke
Published online 26 April 2007 [DOI: 10.1126/science.1142382] (in Science Express Reports)
Abstract » PDF » Supporting Online Material »
相关基因：
CDKN2A
Official Symbol: CDKN2A and Name: cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) [Homo sapiens]
Other Aliases: ARF, CDK4I, CDKN2, CMM2, INK4, INK4a, MLM, MTS1, TP16, p14, p14ARF, p16, p16INK4, p16INK4a, p19
Other Designations: CDK4 inhibitor p16-INK4; cell cycle negative regulator beta; cyclin-dependent kinase inhibitor 2A; cyclin-dependent kinase inhibitor p16; multiple tumor suppressor 1
Location: 9p21
Chromosome: 9 Annotation: NC_000009.10 (21984489..21957750, complement)
MIM: 600160
GeneID: 1029
CDKN2B
Official Symbol: CDKN2B and Name: cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4) [Homo sapiens]
Other Aliases: INK4B, MTS2, P15, TP15
Other Designations: CDK inhibitory protein; CDK4B inhibitor; cyclin-dependent kinase 4 inhibitor B; cyclin-dependent kinase inhibitor 2B; cyclin-dependent kinases 4 and 6 binding protein; multiple tumor suppressor 2; p14_CDK inhibitor; p14_INK4B; p15 CDK inhibitor; p15_INK4B
Location: 9p21
Chromosome: 9 Annotation: NC_000009.10 (21999311..21992901, complement)
MIM: 600431
GeneID: 1030
IGF2BP2
Official Symbol: IGF2BP2 and Name: insulin-like growth factor 2 mRNA binding protein 2 [Homo sapiens]
Other Aliases: IMP-2, IMP2, VICKZ2, p62
Other Designations: IGF II mRNA binding protein 2; IGF-II mRNA-binding protein 2
Location: 3q27.2
Chromosome: 3 Annotation: NC_000003.10 (187025520..186844220, complement)
MIM: 608289
GeneID: 10644
CDKAL1
Official Symbol: CDKAL1 and Name: CDK5 regulatory subunit associated protein 1-like 1 [Homo sapiens]
Other Aliases: FLJ20342, FLJ46705, MGC75469
Location: 6p22.3
Chromosome: 6 Annotation: NC_000006.10 (20642666..21339742)
GeneID: 54901
作者简介：
Michael Boehnke, Ph.D.
Richard G. Cornell Collegiate Professor of Biostatistics
Professional Summary
Michael Boehnke is the Richard G. Cornell Collegiate Professor of Biostatistics and Director of the University of Michigan Center for Statistical Genetics and Genome Science Training Program. He received his Ph.D. in Biomathematics from UCLA in 1983 and joined the faculty in Biostatistics at Michigan in 1984. Dr. Boehnke's research focuses on problems of study design and statistical analysis of human genetic data, with a particular emphasis on development and application of statistical methods for human gene mapping. He is principal investigator of the Finland-United States Investigation of NIDDM Genetics (FUSION) Study, which seeks to identify genetic variants that predispose to type 2 diabetes. He also is active in studies of the genetics of schizophrenia, bipolar disorder, glaucoma, and several other eye diseases.
Courses Taught
BIOSTAT666: Statistical Models and Numerical Methods in Human Genetics Syllabus (PDF)
BIOSTAT866: Advanced Topics in Genetic Modeling
Education
Ph.D., Biomathematics, UCLA, 1983
B.A., Mathematics, University of Oregon, 1977
Research Interest & Projects
Design and Analysis of Human Gene Mapping
Studies Identifying Genes for Type 2 Diabetes: FUSION
Pritzker Neuropsychiatric Disorders Research Consortium
Targeted Genetics Analysis of T2D and Quantitative Traits
Genomic Analysis of Schizophrenia
Molecular Genetics of Primary Open-Angle Glaucoma
Molecular Epidemiology of Colorectal Cancer
National Center for Integrative Biomedical Informatics
Selected Publications
Willer C. J., Scott L. J., Bonnycastle L. L., Jackson A. U., Chines P., Pruim R., Bark C. W., Tsai Y. Y., Pugh E. W., Doheny K. F., Kinnunen L., Mohlke K. L., Valle T. T., Bergman R. N., Tuomilehto J., Collins F. S., Boehnke M. (2006). Tag SNP selection for Finnish individuals based on the CEPH Utah HapMap database. Genetic Epidemiology, 30, 180-190.
Skol A. D., Scott L. J., Abecasis G. R., Boehnke M. (2006). Joint analysis is more efficient for whole genome association studies. Nature Genetics, 38, 209-213.
Li M., Boehnke M., and Abecasis G. R. (2005). Joint modeling of linkage and association: identifying SNPs responsible for a linkage signal. American Journal of Human Genetics, 76, 934-949.
Hauser E. R., Watanabe R. M., Duren W. L., Bass M. P., Langefeld C. D., and Boehnke M. (2004). Ordered subset analysis in genetic linkage mapping of complex traits. Genetic Epidemiology, 27, 53-63.
HSilander K., Mohlke K. L., Scott L. J., Peck E. C., Hollstein P., Skol A D., Deloukas P., ... ,Boehnke M., and Collins F. S. (2004). Genetic variation near the Hepatocye Nuclear Factor-4 Alpha gene predicts susceptibility to type 2 diabetes. Diabetes, 53, 1141-1149.
Silander K., Scott L.J., Valle T.T., Mohlke K.L., Stringham H.M., ..., Collins F.S., and Boehnke M. (2004). A large set of Finnish affected sibling pair families with type 2 diabetes suggests susceptibility loci on chromosomes 6, 11, and 14 Diabetes, 53, 821-829.
Professional Affiliations
American Society for Human Genetics
American Statistical Association
Biometric Society
International Genetic Epidemiology Society
Additional Information
Director, Center for Statistical Genetics
http://csg.sph.umich.edu/
Director, Genome Science Training Program
http://csg.sph.umich.edu//training/
