UW Genome Sciences

The Trask group studies large-scale facets of genome organization. Our work relies on continued development of fluorescence in situ hybridization (FISH), a means of fluorescently tagging specific DNA sequences in chromosomes or nuclei, and flow cytometry, a technology for isolating specific chromosomes for molecular analyses based on their DNA content.

One aspect of genomic organization under study is the arrangement of DNA within the interphase nucleus. Two meters of DNA are packed within each nucleus in interphase, the stage when transcription, repair, and replication occur. FISH is used to mark sites of sequences lying at known distances from each other on the same chromosome (or on different chromosomes). By comparing interphase distances between these points to predictions of various physical models, such as that of a random-walk, we hope to learn which arrangements, if any, are dictated by functional constraints and which can be explained by the physical forces acting on these large molecules.

The structure, function, and evolution of some of the more complex and variable regions of the human genome are also under investigation. One project focuses on the subtelomeric regions of human chromosomes. These regions are a patchwork of sequence-blocks that are duplicated near the ends of multiple chromosomes. They exhibit remarkable polymorphism: the number and location of large blocks can vary among individuals. Because these segments can contain genes, the compositional variability of subtelomeric DNA may have phenotypic consequences. A combination of molecular and cytogenetic techniques is currently being used to unravel the structure and function of these highly dynamic regions of the genome.

In addition, we are studying the large and complex duplications encompassing members of the olfactory receptor gene family. Members of this large gene family are distributed over 40 sites in the human genome, yet each sensory neuron expresses only one gene. In order to determine how the expressed repertoire of olfactory receptors has evolved and is regulated, we are analyzing the genomic organization and function of these genes in mouse and man.

Selected Publications:

McPherson JD, Marra M, Hillier L, Waterston RH, Chinwalla A, Wallis  J, Sekhon M, Wylie K, Mardis ER, Wilson RK, Fulton R, Kucaba TA,  Wagner-McPherson C, Barbazuk WB, Gregory SG, Humphray SJ, French L,  Evans RS, Bethel G, Whittaker A, Holden JL, McCann OT, Dunham A,  Soderlund C, Scott CE, Bentley DR, Schuler G, Chen HC, Jang W, Green  ED, Idol JR, Maduro VV, Montgomery KT, Lee E, Miller A, Emerling S,  Kucherlapati, Gibbs R, Scherer S, Gorrell JH, Sodergren E, Clerc- Blankenburg K, Tabor P, Naylor S, Garcia D, de Jong PJ, Catanese JJ,  Nowak N, Osoegawa K, Qin S, Rowen L, Madan A, Dors M, Hood L, Trask  B, Friedman C, Massa H, Cheung VG, Kirsch IR, Reid T, Yonescu R,  Weissenbach J, Bruls T, Heilig R, Branscomb E, Olsen A, Doggett N,  Cheng JF, Hawkins T, Myers RM, Shang J, Ramirez L, Schmutz J,  Velasquez O, Dixon K, Stone NE, Cox DR, Haussler D, Kent WJ, Furey T,  Rogic S, Kennedy S, Jones S, Rosenthal A, Wen G, Schilhabel M,  Gloeckner G, Nyakatura G, Siebert R, Schlegelberger B, Korenberg J,  Chen XN, Fujiyama A, Hattori M, Toyoda A, Yada T, Park HS, Sakaki Y,  Shimizu N, Asakawa S, Kawasaki K, Sasaki T, Shintani A, Shimizu A,  Shibuya K, Kudoh J, Minoshima S, Ramser J, Seranski P, Hoff C,  Poustka A, Reinhardt R, Lehrach H. A physical map of the human  genome. Nature 409:934-941, 2001.

Olivier M, Aggarwal A, Allen J, Almendras AA, Bajorek ES, Beasley EM,  Brady SD, Bushard JM, Bustos VI, Chu A, Chung TR, De Witte A, Denys  ME, Dominguez R, Fang NY, Foster BD, Freudenberg RW, Hadley D,  Hamilton LR, Jeffrey TJ, Kelly L, Lazzeroni L, Levy MR, Lewis SC, Liu  X, Lopez FJ, Louie B, Marquis JP, Martinez RA, Matsuura MK, Misherghi  NS, Norton JA, Olshen A, Perkins SM, Perou AJ, Piercy C, Piercy M,  Qin F, Reif T, Sheppard K, Shokoohi V, Smick GA, Sun WL, Stewart EA,  Fernando J, Tejeda, Tran NM, Trejo T, Vo NT, Yan SC, Zierten DL, Zhao  S, Sachidanandam R, Trask BJ, Myers RM, Cox DR. A high-resolution  radiation hybrid map of the human genome draft sequence. Science  291:1298-1302, 2001.

Bailey JA, Yavor AM, Massa HF, Trask BJ, Eichler EE. Segmental  duplications: organization and impact within the current human genome  project assembly. Genome Res 11:1005-1017, 2001.

Kouros-Mehr H, Pintchovski S, Melnyk J, Chen YJ, Friedman C, Trask B,  Shizuya H. Identification of non-functional human VNO receptor genes  provides evidence for vestigiality of the human VNO. Chem Senses  26:1167-1174, 2001.

Lane RP, Roach JC, Lee IY, Boysen C, Smit A, Trask BJ, Hood L.  Genomic analysis of the olfactory receptor region of the mouse and  human T-cell receptor alpha/delta loci. Genome Res 12:81-87, 2002.

Lane RP, Cutforth T, Axel R, Hood L, Trask BJ. Sequence analysis of  mouse vomeronasal receptor gene clusters reveals common promoter  motifs and a history of recent expansion. Proc Natl Acad Sci U S A  99:291-296, 2002.

Young JM, Friedman C, Williams EM, Ross JA, Tonnes-Priddy L, Trask  BJ. Different evolutionary processes shaped the mouse and human  olfactory receptor gene families. Hum Mol Genet 11:535-546, 2002.

Mefford HC, Trask BJ. The complex structure and dynamic evolution of  human subtelomeres. Nat Rev Genet 3:91-102, 2002.

Gygi MP, Ferguson MD, Mefford HC, Lund KP, O'Day C, Zhou P, Friedman  C, van den Engh G, Stolowitz ML, Trask BJ. Use of fluorescent  sequence-specific polyamides to discriminate human chromosomes by  microscopy and flow cytometry. Nucleic Acids Res 30:2790-2799, 2002.

Tanaka H, Tapscott SJ, Trask BJ, Yao MC. Short inverted repeats  initiate gene amplification through the formation of a large DNA  palindrome in mammalian cells. Proc Natl Acad Sci U S A 99:8772-8777,  2002.

Sultana R, Yu CE, Yu J, Munson J, Chen D, Hua W, Estes A, Cortes F,  de la Barra F, Yu D, Haider ST, Trask BJ, Green ED, Raskind WH,  Disteche CM, Wijsman E, Dawson G, Storm DR, Schellenberg GD,  Villacres EC. Identification of a novel gene on chromosome 7q11.2  interrupted by a translocation breakpoint in a pair of autistic  twins. Genomics 80:129-134, 2002.

Trask BJ. Human cytogenetics: 46 chromosomes, 46 years and counting.  Nat Rev Genet 3:769-778, 2002.

Fan Y, Linardopoulou E, Friedman C, Williams E, Trask BJ. Genomic  structure and evolution of the ancestral chromosome fusion site in  2q13-2q14.1 and paralogous regions on other human chromosomes. Genome  Res 12:1651-1662, 2002.

Fan Y, Newman T, Linardopoulou E, Trask BJ. Gene content and function  of the ancestral chromosome fusion site in human chromosome  2q13-2q14.1 and paralogous regions. Genome Res 12:1663-1672, 2002.

Newman T, Trask BJ. Complex evolution of 7E olfactory receptor genes  in segmental duplications. Genome Res 13:781-793, 2003.

Heilig R, Eckenberg R, Petit JL, Fonknechten N, Da Silva C, Cattolico  L, Levy M, Barbe V, de Berardinis V, Ureta-Vidal A, Pelletier E, Vico  V, Anthouard V, Rowen L, Madan A, Qin S, Sun H, Du H, Pepin K,  Artiguenave F, Robert C, Cruaud C, Bruls T, Jaillon O, Friedlander L,  Samson G, Brottier P, Cure S, Segurens B, Aniere F, Samain S,  Crespeau H, Abbasi N, Aiach N, Boscus D, Dickhoff R, Dors M, Dubois  I, Friedman C, Gouyvenoux M, James R, Mairey-Estrada B, Mangenot S,  Martins N, Menard M, Oztas S, Ratcliffe A, Shaffer T, Trask B,  Vacherie B, Bellemere C, Belser C, Besnard-Gonnet M, Bartol-Mavel D,  Boutard M, Briez-Silla S, Combette S, Dufosse-Laurent V, Ferron C,  Lechaplais C, Louesse C, Muselet D, Magdelenat G, Pateau E, Petit E,  Sirvain-Trukniewicz P, Trybou A, Vega-Czarny N, Bataille E, Bluet E,  Bordelais I, Dubois M, Dumont C, Guerin T, Haffray S, Hammadi R,  Muanga J, Pellouin V, Robert D, Wunderle E, Gauguet G, Roy A, Sainte- Marthe L, Verdier J, Verdier-Discala C, Hillier L, Fulton L,  McPherson J, Matsuda F, Wilson R, Scarpelli C, Gyapay G, Wincker P,  Saurin W, Quetier F, Waterston R, Hood L, Weissenbach J. The DNA  sequence and analysis of human chromosome 14. Nature 421:601-607, 2003.

Young JM, Shykind BM, Lane RP, Tonnes-Priddy L, Ross JA, Walker M,  Williams EM, Trask BJ. Odorant receptor expressed sequence tags  demonstrate olfactory expression of over 400 genes, extensive  alternate splicing and unequal expression levels. Genome Biol 4:R71,  2003.

Gibbs RA, Weinstock GM, Metzker ML, Muzny DM, Sodergren EJ, Scherer  S, Scott G, Steffen D, Worley KC, Burch PE, Okwuonu G, Hines S, Lewis  L, DeRamo C, Delgado O, Dugan-Rocha S, Miner G, Morgan M, Hawes A,  Gill R, Celera, Holt RA, Adams MD, Amanatides PG, Baden-Tillson H,  Barnstead M, Chin S, Evans CA, Ferriera S, Fosler C, Glodek A, Gu Z,  Jennings D, Kraft CL, Nguyen T, Pfannkoch CM, Sitter C, Sutton GG,  Venter JC, Woodage T, Smith D, Lee HM, Gustafson E, Cahill P, Kana A,  Doucette-Stamm L, Weinstock K, Fechtel K, Weiss RB, Dunn DM, Green  ED, Blakesley RW, Bouffard GG, De Jong PJ, Osoegawa K, Zhu B, Marra  M, Schein J, Bosdet I, Fjell C, Jones S, Krzywinski M, Mathewson C,  Siddiqui A, Wye N, McPherson J, Zhao S, Fraser CM, Shetty J, Shatsman  S, Geer K, Chen Y, Abramzon S, Nierman WC, Havlak PH, Chen R, Durbin  KJ, Egan A, Ren Y, Song XZ, Li B, Liu Y, Qin X, Cawley S, Worley KC,  Cooney AJ, D'Souza LM, Martin K, Wu JQ, Gonzalez-Garay ML, Jackson  AR, Kalafus KJ, McLeod MP, Milosavljevic A, Virk D, Volkov A, Wheeler  DA, Zhang Z, Bailey JA, Eichler EE, Tuzun E, Birney E, Mongin E,  Ureta-Vidal A, Woodwark C, Zdobnov E, Bork P, Suyama M, Torrents D,  Alexandersson M, Trask BJ, Young JM, Huang H, Wang H, Xing H, Daniels  S, Gietzen D, Schmidt J, Stevens K, Vitt U, Wingrove J, Camara F, Mar  Alba M, Abril JF, Guigo R, Smit A, Dubchak I, Rubin EM, Couronne O,  Poliakov A, Hubner N, Ganten D, Goesele C, Hummel O, Kreitler T, Lee  YA, Monti J, Schulz H, Zimdahl H, Himmelbauer H, Lehrach H, Jacob HJ,  Bromberg S, Gullings-Handley J, Jensen-Seaman MI, Kwitek AE, Lazar J,  Pasko D, Tonellato PJ, Twigger S, Ponting CP, Duarte JM, Rice S,  Goodstadt L, Beatson SA, Emes RD, Winter EE, Webber C, Brandt P,  Nyakatura G, Adetobi M, Chiaromonte F, Elnitski L, Eswara P, Hardison  RC, Hou M, Kolbe D, Makova K, Miller W, Nekrutenko A, Riemer C,  Schwartz S, Taylor J, Yang S, Zhang Y, Lindpaintner K, Andrews TD,  Caccamo M, Clamp M, Clarke L, Curwen V, Durbin R, Eyras E, Searle SM,  Cooper GM, Batzoglou S, Brudno M, Sidow A, Stone EA, Venter JC,  Payseur BA, Bourque G, Lopez-Otin C, Puente XS, Chakrabarti K,  Chatterji S, Dewey C, Pachter L, Bray N, Yap VB, Caspi A, Tesler G,  Pevzner PA, Haussler D, Roskin KM, Baertsch R, Clawson H, Furey TS,  Hinrichs AS, Karolchik D, Kent WJ, Rosenbloom KR, Trumbower H,  Weirauch M, Cooper DN, Stenson PD, Ma B, Brent M, Arumugam M,  Shteynberg D, Copley RR, Taylor MS, Riethman H, Mudunuri U, Peterson  J, Guyer M, Felsenfeld A, Old S, Mockrin S, Collins F.  Genome  sequence of the Brown Norway rat yields insights into mammalian  evolution. Nature 428:493-521, 2004.

Lane RP, Young J, Newman T, Trask BJ. Species specificity in rodent  pheromone receptor repertoires. Genome Res 14:603-608, 2004.

Sebat J, Lakshmi B, Troge J, Alexander J, Young J, Lundin P, Maner S,  Massa H, Walker M, Chi M, Navin N, Lucito R, Healy J, Hicks J, Ye K,  Reiner A, Gilliam TC, Trask B, Patterson N, Zetterberg A, Wigler M.  Large-scale copy number polymorphism in the human genome. Science  305:525-528, 2004.

Loo LW, Grove DI, Williams EM, Neal CL, Cousens LA, Schubert EL,  Holcomb IN, Massa HF, Glogovac J, Li CI, Malone KE, Daling JR, Delrow  JJ, Trask BJ, Hsu L, Porter PL. Array comparative genomic  hybridization analysis of genomic alterations in breast cancer  subtypes. Cancer Res 64:8541-8549, 2004.

Young JM, Kambere M, Trask BJ, Lane RP. Divergent V1R repertoires in  five species: Amplification in rodents, decimation in primates, and a  surprisingly small repertoire in dogs. Genome Res 15:231-240, 2005.

Rowen L, Williams E, Glusman G, Linardopoulou E, Friedman C, Ahearn  ME, Seto J, Boysen C, Qin S, Wang K, Kaur A, Bloom S, Hood L, Trask  BJ. Interchromosomal segmental duplications explain the unusual  structure of PRSS3, the gene for an inhibitor-resistant trypsinogen.  Mol Biol Evol 22:1712-1720, 2005.

Linardopoulou EV, Williams EM, Fan Y, Friedman C, Young JM, Trask  BJ.  Human subtelomeres are hot spots of interchromosomal  recombination and segmental duplication.  Nature 437:94-100, 2005.

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