One of the most challenging problems in biology and medicine is defining the relationship between genotype and phenotype. The development and application of genetic linkage mapping has lead to the identification of candidate genes for hundreds of rare human diseases revealing simple inheritance patterns. Although linkage has been successfully applied to mapping rare human diseases, whole genome scans for linkage to common human diseases such as cardiovascular disease, hypertension, and asthma, have yielded less favorable results. Many of these diseases arise from the interaction of multiple genes combined with environmental modifiers. Thus, the relative risk of any given effect is small making association analysis more practical as a method for exploring disease susceptibility/resistance in humans.

For more than a decade, my group has been interested in the identification and typing of common sequence variations in the human genome known as single nucleotide polymorphisms (SNPs) in an effort to gain an understanding of the patterns of sequence variation in human genome and to improve approaches for association mapping of common human diseases. In collaboration with a number of groups, we are exploring the genetics of cardiovascular disease risk in human populations. We are also developing and testing novel SNP and haplotype-based approaches for association mapping in humans, and we are exploring the relationships that may exist between genotype and trait expression at the RNA and protein levels in humans.

Selected Publications:

Common and rare von Willebrand factor (VWF) coding variants, von Willebrand factor levels, and factor VIII levels in African Americans. Johnsen JM, Auer PL, Morrison AC, Jiao S, Wei P, Haessler J, Fox K, McGee SR, Smith JD, Carlson CS, Smith N, Boerwinkle E, Kooperberg C, Nickerson DA, Rich SS, Green D, Peters U, Cushman M, Reiner AP. Blood 2013 May 20 [Epub ahead of print]

Mutations in KCTD1 CauseScalp-Ear-Nipple Syndrome. Marneros AG, Beck AE, Turner EH, McMillin MJ, Edwards MJ, Field M, de Macena Sobreira NL, Perez AB, Fortes JA, Lampe AK, Giovannucci Uzielli ML, Gordon CT, Plessis G, Le Merrer M, Amiel J, Reichenberger E, Shively KM, Cerrato F, Labow BI, Tabor HK, Smith JD, Shendure J, Nickerson DA, Bamshad MJ; University of Washington Center for Mendelian Genomics. Am J Hum Genet. 2013 Apr 4;92(4):621-6.

Exome Sequencing and Genome-Wide Linkage Analysis in 17 Families Illustrate the Complex Contribution of TTN Truncating Variants to Dilated Cardiomyopathy. Norton N, Li D, Rampersaud E, Morales A, Martin ER, Zuchner S, Guo S, Gonzalez M, Hedges DJ, Robertson PD, Krumm N, Nickerson DA, Hershberger RE; National Heart, Lung, and Blood Institute GO Exome Sequencing Project and the Exome Sequencing Project Family Studies Project Team. Circ Cardiovasc Genet. 2013 Apr 1;6(2):144-53.

Utilizing graph theory to select the largest set of unrelated individuals for genetic analysis. Staples J, Nickerson DA, Below JE. Genet Epidemiol. 2013 Feb;37(2):136-41.

Whole-genome analysis reveals that mutations in inositol polyphosphate phosphatase-like 1 cause opsismodysplasia. Below JE, Earl DL, Shively KM, McMillin MJ, Smith JD, Turner EH, Stephan MJ, Al-Gazali LI, Hertecant JL, Chitayat D, Unger S, Cohn DH, Krakow D, Swanson JM, Faustman EM, Shendure J, Nickerson DA, Bamshad MJ; University of Washington Center for Mendelian Genomics. Am J Hum Genet. 2013 Jan 10;92(1):137-43.

Mutations in ECEL1 cause distal arthrogryposis type 5D. McMillin MJ, Below JE, Shively KM, Beck AE, Gildersleeve HI, Pinner J, Gogola GR, Hecht JT, Grange DK, Harris DJ, Earl DL, Jagadeesh S, Mehta SG, Robertson SP, Swanson JM, Faustman EM, Mefford HC, Shendure J, Nickerson DA, Bamshad MJ; University of Washington Center for Mendelian Genomics. Am J Hum Genet. 2013 Jan 10;92(1):150-6.

Analysis of 6,515 exomes reveals the recent origin of most human protein-coding variants. Fu W, O'Connor TD, Jun G, Kang HM, Abecasis G, Leal SM, Gabriel S, Rieder MJ, Altshuler D, Shendure J, Nickerson DA, Bamshad MJ; NHLBI Exome Sequencing Project, Akey JM. Nature. 2013 Jan 10;493(7431):216-20.

Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders. O'Roak BJ, Vives L, Fu W, Egertson JD, Stanaway IB, Phelps IG, Carvill G, Kumar A, Lee C, Ankenman K, Munson J, Hiatt JB, Turner EH, Levy R, O'Day DR, Krumm N, Coe BP, Martin BK, Borenstein E, Nickerson DA, Mefford HC, Doherty D, Akey JM, Bernier R, Eichler EE, Shendure J. Science. 2012 Dec 21;338(6114):1619-22.

Copy number variation detection and genotyping from exome sequence data. Krumm N, Sudmant PH, Ko A, O'Roak BJ, Malig M, Coe BP; NHLBI Exome Sequencing Project, Quinlan AR, Nickerson DA, Eichler EE. Genome Res. 2012 Aug;22(8):1525-32.

Evolution and functional impact of rare coding variation from deep sequencing of human exomes. Tennessen JA, Bigham AW, O'Connor TD, Fu W, Kenny EE, Gravel S, McGee S, Do R, Liu X, Jun G, Kang HM, Jordan D, Leal SM, Gabriel S, Rieder MJ, Abecasis G, Altshuler D, Nickerson DA, Boerwinkle E, Sunyaev S, Bustamante CD, Bamshad MJ, Akey JM; Broad GO; Seattle GO; NHLBI Exome Sequencing Project. Science. 2012 Jul 6;337(6090):64-9.

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