生物谷報(bào)道：一項(xiàng)考查人數(shù)超過35000人,、覆蓋整個(gè)人類基因組的研究表明,，與骨關(guān)節(jié)炎相關(guān)的常見遺傳突變?cè)谌梭w身高上起著重要的作用,。此項(xiàng)研究1月13日刊登在《自然—遺傳學(xué)》（Nature Genetics）上,。研究小組部分成員來自美國國立衛(wèi)生研究院,。
在此項(xiàng)最新的基因組范圍內(nèi)的掃描中,，與身高最為相關(guān)的基因突變是人類基因組的一個(gè)特定區(qū)域,，該區(qū)域被認(rèn)為是影響著生長分化因子5（growth differentiation factor 5；GDF5）基因的表達(dá),。GDF5參與調(diào)控腿骨和其他長骨的軟骨發(fā)育,。很少有GDF5基因的突變體表明它與骨骼發(fā)育相關(guān)，越來越多的突變體將該基因的常見突變體與臀部,、膝蓋的骨關(guān)節(jié)炎（osteoarthritis）的易感性聯(lián)系起來,。
“我們研究的人類常見突變體中主要有兩個(gè)明顯特征，一是身材短小,，二是像之前所述的那樣,，具有較高的骨關(guān)節(jié)炎的發(fā)病率。” 此項(xiàng)研究的通訊作者Karen L. Mohlke介紹說,，她是北卡羅來納大學(xué)教堂山分校的教授,，“我們的研究暗示著在遺傳導(dǎo)致的身高缺陷與骨關(guān)節(jié)炎之間，骨生長和發(fā)育起著重要的作用,。”
Mohlke和她的同事強(qiáng)調(diào)說,，新的研究僅僅涉及到部分影響身高的遺傳基因，這表明要對(duì)身高這一復(fù)雜的人類性狀進(jìn)行完整的描述仍需更多更深入的研究,。
許多因子都影響著人體的身高,，包括遺傳、產(chǎn)前環(huán)境,、飲食等,。當(dāng)前，科學(xué)家認(rèn)為影響人類身高的多樣性中，將近80%來自于遺傳,。但是,，這個(gè)最新的遺傳突變體，以及另外一個(gè)最新發(fā)現(xiàn)的與身高相關(guān)的遺傳突變體HMGA2,，兩者對(duì)人體身高的影響之和仍不到1%,。
“很多遺傳突變對(duì)身高的影響都很小，所以需要采集更大量的數(shù)據(jù)才能真正找出這些基因,。”美國國立人類基因組研究所（National Human Genome Research Institute,；NHGRI）的主任Francis S. Collins介紹說，他是此項(xiàng)研究的共同作者,。（來源：生命經(jīng)緯）
生物谷推薦原始出處：
Nature Genetics
Published online: 13 January 2008 | doi:10.1038/ng.74
Common variants in the GDF5-UQCC region are associated with variation in human height
Serena Sanna1,2,19, Anne U Jackson1,19, Ramaiah Nagaraja3, Cristen J Willer1, Wei-Min Chen1,4, Lori L Bonnycastle5, Haiqing Shen6, Nicholas Timpson7,8, Guillaume Lettre9, Gianluca Usala2, Peter S Chines5, Heather M Stringham1, Laura J Scott1, Mariano Dei2, Sandra Lai2, Giuseppe Albai2, Laura Crisponi2, Silvia Naitza2, Kimberly F Doheny10, Elizabeth W Pugh10, Yoav Ben-Shlomo7, Shah Ebrahim11, Debbie A Lawlor7,8, Richard N Bergman12, Richard M Watanabe12,13, Manuela Uda2, Jaakko Tuomilehto14, Josef Coresh15, Joel N Hirschhorn9, Alan R Shuldiner6,16, David Schlessinger3, Francis S Collins5, George Davey Smith7,8, Eric Boerwinkle17, Antonio Cao2, Michael Boehnke1, Gonçalo R Abecasis1 & Karen L Mohlke18
Identifying genetic variants that influence human height will advance our understanding of skeletal growth and development. Several rare genetic variants have been convincingly and reproducibly associated with height in mendelian syndromes, and common variants in the transcription factor gene HMGA2 are associated with variation in height in the general population1. Here we report genome-wide association analyses, using genotyped and imputed markers, of 6,669 individuals from Finland and Sardinia, and follow-up analyses in an additional 28,801 individuals. We show that common variants in the osteoarthritis-associated locus2GDF5-UQCC contribute to variation in height with an estimated additive effect of 0.44 cm (overall P < 10-15). Our results indicate that there may be a link between the genetic basis of height and osteoarthritis, potentially mediated through alterations in bone growth and development.
Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109, USA.
Istituto di Neurogenetica e Neurofarmacologia (INN), Consiglio Nazionale delle Ricerche, c/o Cittadella Universitaria di Monserrato, Monserrato, Cagliari 09042, Italy.
Gerontology Research Center, National Institute on Aging, Baltimore, Maryland 21224, USA.
Division of Biostatistics and Epidemiology, Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
Genome Technology Branch, National Human Genome Research Institute, Bethesda, Maryland 20892, USA.
Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Department of Social Medicine, University of Bristol, Canynge Hall, Bristol BS8 2PR, UK.
Medical Research Council (MRC) Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Canynge Hall, Bristol BS8 2PR, UK.
Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Seven Cambridge Center, Cambridge, Massachusetts 02142, USA.
Center for Inherited Disease Research (CIDR), Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland 21224, USA.
London School of Hygiene and Tropical Medicine, University of London, London WC1E 7HT, UK.
Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.
Diabetes Unit, Department of Health Promotion and Chronic Disease Prevention, National Public Health Institute, 00300 Helsinki, and Department of Public Health, University of Helsinki, 00014 Helsinki, Finland.
Welch Center for Prevention, Epidemiology and Clinical Research, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA.
Geriatric Research and Education Center, Veterans Administration Medical Center, Baltimore, Maryland 21201, USA.
Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas 77225, USA.
Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
These authors contributed equally to this work.
Correspondence to: Karen L Mohlke18 e-mail: [email protected]
Correspondence to: Gonçalo R Abecasis1 e-mail: [email protected]
