生物谷報(bào)道：通過一項(xiàng)基因譜相關(guān)分析研究鑒定了四種較新的鑒定基因――定位在9號(hào)染色體上的CDKN2A, CDKN2B基因,，定位在3號(hào)染色體上的IGF2BP2基因以及CDKAL1基因――這項(xiàng)分析研究中,，研究者詳細(xì)調(diào)查了數(shù)千人群的染色體組來鑒別單核苷酸多態(tài)性（SNPs）。國(guó)際小組也證實(shí)了既往的發(fā)現(xiàn)：另六個(gè)基因遺傳性變型――TCF7L2, SLC30A8, HHEX, PPARG, KCNJ11, 以及FTO――與糖尿病發(fā)展的風(fēng)險(xiǎn)性增高相關(guān),。
糖尿病一級(jí)親屬的糖尿病發(fā)生高風(fēng)險(xiǎn)性是一般人群的3.5倍，但迄今為止鑒別糖尿病的遺傳危害因子的發(fā)現(xiàn)局限,。進(jìn)一步而言,，需定義這種疾病的基因結(jié)構(gòu)以及鑒別疾病發(fā)病機(jī)理中的生物學(xué)途徑，1161例芬蘭2型糖尿病患者和1174例芬蘭正常葡萄糖耐量受試者參與芬蘭－美國(guó)年青人非胰島素依賴型糖尿病(FUSION) 和國(guó)家的FINRISK研究,。通過SNPs關(guān)聯(lián)分析后,，研究者證實(shí)了染色體的三個(gè)新區(qū)域影響2型糖尿病的發(fā)生。此三個(gè)基因變異型定位于附近被認(rèn)為調(diào)節(jié)胰島素和那些在胰臟內(nèi)促進(jìn)胰島素分泌增長(zhǎng)的基因,。除了鑒定出CDKN2A/CDKN2B,，IGF2BP2, 和 CDKAL1外，研究者也檢測(cè)11號(hào)染色體上既往不含有注釋基因的區(qū)域,。這樣的結(jié)果在兩個(gè)獨(dú)立樣本中被證實(shí),，第一個(gè)樣本來自Wellcome病例對(duì)照協(xié)會(huì)，第二個(gè)為在DGI內(nèi)瑞典和芬蘭人的染色體組,。既往鑒定的變異基因型-- TCF7L2, SLC30A8, HHEX, PPARG, KCNJ11和FTO—也被研究者證實(shí),，此結(jié)果有助于使得研究糖尿病發(fā)生的遺傳性變型數(shù)目達(dá)到10. 研究人員接著檢測(cè)了芬蘭受試者的所有10項(xiàng)糖尿病相關(guān)遺傳性變型的染色體組，并構(gòu)建了一個(gè)logistic回歸模型預(yù)測(cè)每個(gè)受試者的糖尿病風(fēng)險(xiǎn)性,。通過這樣,，他們鑒定了存在遺傳性變型的受試者發(fā)生糖尿病的風(fēng)險(xiǎn)達(dá)四倍之高，研究小組提到：通過這樣他們看發(fā)現(xiàn)個(gè)體預(yù)防醫(yī)學(xué)項(xiàng)目的潛在價(jià)值,。研究者詳細(xì)調(diào)查了數(shù)千人群的大樣本染色體組來鑒別單核苷酸多態(tài)性（SNPs）,。
《科學(xué)》刊物中2007年4月26號(hào)的作者Dr Laura Scott（密西根州Ann Arbor大學(xué)）在文章中寫到：“研究的三組需要大量樣本，我們能肯定糖尿病的新風(fēng)險(xiǎn)因子已經(jīng)鑒定出來,，每個(gè)基因的發(fā)現(xiàn)都有助于發(fā)病機(jī)制的闡明,，所有的蛋白及相關(guān)途徑都代表著糖尿病預(yù)防或治療的藥物潛在靶位點(diǎn)。
原文出處：
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 »
相關(guān)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
作者簡(jiǎn)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/
