Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 7 November 2008:
Vol. 322. no. 5903, pp. 881 - 888
DOI: 10.1126/science.1156409
Prev | Table of Contents | Next

Review

Genetic Mapping in Human Disease

David Altshuler,1,2,3,4,5* Mark J. Daly,1,2,5* Eric S. Lander1,6,7,8*

Genetic mapping provides a powerful approach to identify genes and biological processes underlying any trait influenced by inheritance, including human diseases. We discuss the intellectual foundations of genetic mapping of Mendelian and complex traits in humans, examine lessons emerging from linkage analysis of Mendelian diseases and genome-wide association studies of common diseases, and discuss questions and challenges that lie ahead.

1 Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
2 Center for Human Genetic Research and Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
3 Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
4 Department of Genetics, Harvard Medical School, Boston, MA 02114, USA.
5 Department of Medicine, Harvard Medical School, Boston, MA 02114, USA.
6 Department of Systems Biology, Harvard Medical School, Boston, MA 02114, USA.
7 Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
8 Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.

* To whom correspondence should be addressed. E-mail: altshuler{at}molbio.mgh.harvard.edu (D.A.); mjdaly{at}chgr.mgh.harvard.edu (M.J.D.); lander{at}broad.mit.edu (E.S.L.)

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Genetic diagnosis by whole exome capture and massively parallel DNA sequencing.
M. Choi, U. I. Scholl, W. Ji, T. Liu, I. R. Tikhonova, P. Zumbo, A. Nayir, A. Bakkaloglu, S. Ozen, S. Sanjad, et al. (2009)
PNAS 106, 19096-19101
   Abstract »    Full Text »    PDF »
IGF2 mRNA-binding protein 2: biological function and putative role in type 2 diabetes.
J. Christiansen, A. M Kolte, T. v O Hansen, and F. C Nielsen (2009)
J. Mol. Endocrinol. 43, 187-195
   Abstract »    Full Text »    PDF »
Pervasive transcription of the eukaryotic genome: functional indices and conceptual implications.
M. E. Dinger, P. P. Amaral, T. R. Mercer, and J. S. Mattick (2009)
Brief Funct Genomic Proteomic 8, 407-423
   Abstract »    Full Text »    PDF »
Genetics and the general physician: insights, applications and future challenges.
J.C. Knight (2009)
QJM 102, 757-772
   Abstract »    Full Text »    PDF »
Transgenerational genetic effects on phenotypic variation and disease risk.
J. H. Nadeau (2009)
Hum. Mol. Genet. 18, R202-R210
   Abstract »    Full Text »    PDF »
Control of fetal hemoglobin: new insights emerging from genomics and clinical implications.
S. L. Thein, S. Menzel, M. Lathrop, and C. Garner (2009)
Hum. Mol. Genet. 18, R216-R223
   Abstract »    Full Text »    PDF »
GRIMP: a web- and grid-based tool for high-speed analysis of large-scale genome-wide association using imputed data.
K. Estrada, A. Abuseiris, F. G. Grosveld, A. G. Uitterlinden, T. A. Knoch, and F. Rivadeneira (2009)
Bioinformatics 25, 2750-2752
   Abstract »    Full Text »    PDF »
Triplet repeat length bias and variation in the human transcriptome.
M. Molla, A. Delcher, S. Sunyaev, C. Cantor, and S. Kasif (2009)
PNAS 106, 17095-17100
   Abstract »    Full Text »    PDF »
Kallikreins: unravelling the genetics of autoimmune glomerulonephritis.
J. Behmoaras, H. T. Cook, and C. D. Pusey (2009)
Nephrol. Dial. Transplant. 24, 2987-2989
   Full Text »    PDF »
Progress in the study of genetic disease: bringing new light to complex problems.
A. Shelling (2009)
Postgrad. Med. J. 85, 505-507
   Full Text »    PDF »
Harnessing the information contained within genome-wide association studies to improve individual prediction of complex disease risk.
D. M. Evans, P. M. Visscher, and N. R. Wray (2009)
Hum. Mol. Genet. 18, 3525-3531
   Abstract »    Full Text »    PDF »
Genome-wide association studies in kidney diseases: Quo Vadis?.
F. Pesce and F. P. Schena (2009)
Nephrol. Dial. Transplant.
   Full Text »    PDF »
Genetics of COPD and Emphysema.
E. S. Wan and E. K. Silverman (2009)
Chest 136, 859-866
   Abstract »    Full Text »    PDF »
Insights into the nature and consequences of our variable genome.
J. C. Knight (2009)
Brief Funct Genomic Proteomic 8, 343-344
   Full Text »    PDF »
Sequencing Genomes: From Individuals to Populations.
K. U. Mir (2009)
Brief Funct Genomic Proteomic 8, 367-378
   Abstract »    Full Text »    PDF »
A probabilistic approach for SNP discovery in high-throughput human resequencing data.
R. Hoberman, J. Dias, B. Ge, E. Harmsen, M. Mayhew, D. J. Verlaan, T. Kwan, K. Dewar, M. Blanchette, and T. Pastinen (2009)
Genome Res. 19, 1542-1552
   Abstract »    Full Text »    PDF »
Genomic Analysis of Left Ventricular Remodeling.
R. Sarwar and S. A. Cook (2009)
Circulation 120, 437-444
   Full Text »    PDF »
Dissecting the phenotype in genome-wide association studies of psychiatric illness.
Cross-Disorder Phenotype Group of the Psychiatric, N. Craddock, K. Kendler, M. Neale, J. Nurnberger, S. Purcell, M. Rietschel, R. Perlis, S. L. Santangelo, T. Schulze, et al. (2009)
The British Journal of Psychiatry 195, 97-99
   Abstract »    Full Text »    PDF »
Association Mapping: Critical Considerations Shift from Genotyping to Experimental Design.
S. Myles, J. Peiffer, P. J. Brown, E. S. Ersoz, Z. Zhang, D. E. Costich, and E. S. Buckler (2009)
PLANT CELL 21, 2194-2202
   Abstract »    Full Text »    PDF »
A chromosome 16 quantitative trait locus regulates allogeneic bone marrow engraftment in nonmyeloablated mice.
T. M. Cao, A. Thomas, Y. Wang, S. Tsai, K. Logronio, and J. A. Shizuru (2009)
Blood 114, 202-210
   Abstract »    Full Text »    PDF »
SNPinfo: integrating GWAS and candidate gene information into functional SNP selection for genetic association studies.
Z. Xu and J. A. Taylor (2009)
Nucleic Acids Res. 37, W600-W605
   Abstract »    Full Text »    PDF »
Pathway and network-based analysis of genome-wide association studies in multiple sclerosis.
S. E. Baranzini, N. W. Galwey, J. Wang, P. Khankhanian, R. Lindberg, D. Pelletier, W. Wu, B. M.J. Uitdehaag, L. Kappos, GeneMSA Consortium, et al. (2009)
Hum. Mol. Genet. 18, 2078-2090
   Abstract »    Full Text »    PDF »
Complex Renal Traits: Role of Adrenergic Genetic Polymorphism.
M. M. Fung and D. T. O'Connor (2009)
J. Am. Soc. Nephrol. 20, 1172-1174
   Full Text »    PDF »
Personalized Medicine: Reality and Reality Checks.
J S. Leeder and S. P Spielberg (2009)
Ann. Pharmacother. 43, 963-966
   Abstract »    Full Text »    PDF »
Genomewide Association Studies -- Illuminating Biologic Pathways.
J. N. Hirschhorn (2009)
N. Engl. J. Med. 360, 1699-1701
   Full Text »    PDF »
High-throughput, high-accuracy array-based resequencing.
J. Zheng, M. Moorhead, L. Weng, F. Siddiqui, V. E. H. Carlton, J. S. Ireland, L. Lee, J. Peterson, J. Wilkins, S. Lin, et al. (2009)
PNAS 106, 6712-6717
   Abstract »    Full Text »    PDF »
Rare Variants of IFIH1, a Gene Implicated in Antiviral Responses, Protect Against Type 1 Diabetes.
S. Nejentsev, N. Walker, D. Riches, M. Egholm, and J. A. Todd (2009)
Science 324, 387-389
   Abstract »    Full Text »    PDF »
Defining the Pathogenicity of DNA Sequence Variation.
C. Y. Ho and C. A. MacRae (2009)
Circ Cardiovasc Genet 2, 95-97
   Full Text »    PDF »
Breathe Deeply into Your Genes!: Genetic Variants and Air Pollution Effects.
A. Baccarelli (2009)
Am. J. Respir. Crit. Care Med. 179, 431-432
   Full Text »    PDF »
Landmarks in the History of Cancer Epidemiology.
P. Greenwald and B. K. Dunn (2009)
Cancer Res. 69, 2151-2162
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)