The long-term goal of our laboratory is to understand the evolution, pathology and mechanisms of recent gene duplication and DNA transposition within the human genome.

Our research specifically addresses a new paradigm that has emerged in the past few years in which particular regions of the human genome have been shown active in the acquisition, duplication and dispersal of large gene-containing genomic segments.

We hypothesize that these 'jumping genomic segments' are part of an ongoing evolutionary process that results in a novel form of large-scale variation in human genomic DNA and contributes rapidly to primate gene evolution.

The large blocks of sequence similarity generated by this process, we further propose provide the substrates for aberrant recombination, thereby leading to recurrent and potentially pathogenic chromosomal structural rearrangements.

The general aims of our research are
1) to investigate the molecular mechanism(s) responsible for such duplications;
2) to evaluate their role in the evolution of the higher primate genome; and
3) to assess their impact in contributing to polymorphism of both normal human chromosomes and chromosomes associated with genetic instability diseases.

Our approach has been to combine bioinformatics, large-scale comparative sequencing, phylogenetics and high-resolution FISH methods to address these questions.

We are committed to the further characterization of these complex regions of the genome and the development of assays to correlate their dynamic structure with chromosome function, gene evolution and human disease. My research philosophy combines various disciplines (evolutionary biology, human genetics/genomics and bioinformatics) to understand the mechanisms and consequences of novel forms of variation in the human genome. Such a synergism of various disciplines provides a powerful strategy to address biological processes of genome evolution. The development of tools and the conditions required to pursue such a holistic approach, with respect to studies of genome evolution, are unprecedented. With the advent of the information age, current large-scale sequencing of genomes and the development of powerful bioinformatics tools, such 'complex' and mulitfaceted research objectives will become increasingly tractable endeavors.

My overall goal is to contribute to this new era of genomics sciences as it applies to evolution and medicine and to impart the value of this scientific design, through teaching and mentorship, to the next generation of scientists.

Selected Publications:

Girirajan S, Rosenfeld JA, Cooper GM, Antonacci F, Siswara P, Itsara A, Vives L, Walsh T, McCarthy SE, Baker C, Mefford HC, Kidd JM, Browning SR, Browning BL, Dickel DE, Levy DL, Ballif BC, Platky K, Farber DM, Gowans GC, Wetherbee JJ, Asamoah A, Weaver DD, Mark PR, Dickerson J, Garg BP, Ellingwood SA, Smith R, Banks VC, Smith W, McDonald MT, Hoo JJ, French BN, Hudson C, Johnson JP, Ozmore JR, Moeschler JB, Surti U, Escobar LF, El-Khechen D, Gorski JL, Kussmann J, Salbert B, Lacassie Y, Biser A, McDonald-McGinn DM, Zackai EH, Deardorff MA, Shaikh TH, Haan E, Friend KL, Fichera M, Romano C, Gecz J, Delisi LE, Sebat J, King MC, Shaffer LG, Eichler EE. (2010). A recurrent 16p12.1 microdeletion supports a two-hit model for severe developmental delay. Nat Genet Mar;42(3):203-9.

Alkan C, Kidd JM, Marques-Bonet T, Aksay G, Antonacci F, Hormozdiari F, Kitzman JO, Baker C, Malig M, Mutlu O, Sahinalp SC, Gibbs RA, Eichler EE. (2009). Personalized copy number and segmental duplication maps using next-generation sequencing. Nat Genet Oct;41(10):1061–7.

Marques-Bonet T, Kidd JM, Ventura M, Graves TA, Cheng Z, Hillier LW, Jiang Z, Baker C, Malfavon-Borja R, Fulton LA, Alkan C, Aksay G, Girirajan S, Siswara P, Chen L, Cardone MF, Navarro A, Mardis ER, Wilson RK, Eichler EE. (2009). A burst of segmental duplications in the genome of the African great ape ancestor. Nature Feb 12;457(7231):877–81.

Itsara A, Cooper GM, Baker C, Girirajan S, Li J, Absher D, Krauss RM, Myers RM, Ridker PM, Chasman DI, Mefford H, Ying P, Nickerson DA, Eichler EE. (2009). Population analysis of large copy number variants and hotspots of human genetic disease. Am J Hum Genet. Feb;84(2):148–61.

Kidd JM, Cooper GM, Donahue WF, Hayden HS, Sampas N, Graves T, Hansen N, Teague B, Alkan C, Antonacci F, Haugen E, Zerr T, Yamada NA, Tsang P, Newman TL, Tuzun E, Cheng Z, Ebling HM, Tusneem N, David R, Gillett W, Phelps KA, Weaver M, Saranga D, Brand A, Tao W, Gustafson E, McKernan K, Chen L, Malig M, Smith JD, Korn JM, McCarroll SA, Altshuler DA, Peiffer DA, Dorschner M, Stamatoyannopoulos J, Schwartz D, Nickerson DA, Mullikin JC, Wilson RK, Bruhn L, Olson MV, Kaul R, Smith DR, Eichler EE. (2008). Mapping and sequencing of structural variation from eight human genomes. Nature May 1;453(7191):56–64.

Jiang Z, Tang H, Ventura M, Cardone MF, Marques-Bonet T, She X, Pevzner P, Eichler EE. (2007). Ancestral reconstruction of segmental duplications reveals punctuated cores of human genome evolution. Nat Genet Nov;39(11):1361–1368 (7 Oct 2007).

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