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Bruce T. Lahn

Professor
blahn@bsd.uchicago.edu
Research Summary
Our lab studies the mechanism of cell fate restriction. The approaches we take fall at the interface of several disciplines, including developmental biology, stem cell biology and epigenetics. Below is a brief summary of our work. The hallmark of multicellular life is the presence of diverse cell types within a single organism, all bearing the same genome but disparate gene expression patterns. In mammals, as in many other taxa, this is accomplished via the progressive differentiation of pluripotent stem cells into a variety of specialized cell types. During this process, cells lose their potential for all but the lineage to which they have become committed. A longstanding but unresolved question in biology is: how is cell fate restricted during somatic differentiation? Furthermore, how is this restriction reversed during reproduction to reestablish pluripotency at the onset of development? Based on emerging data from the literature and our lab, we developed a conceptually simple model, dubbed the “gene occlusion” model, to account for cell fate restriction during somatic development and its reversal during reproduction. The model makes three assertions: (1) A gene’s transcriptional potential can assume either the competent state wherein the gene is responsive to, and can be activated by, trans-acting factors in the cellular milieu, or the occluded state wherein the gene is blocked by cis-acting, chromatin-based mechanisms from responding to trans factors such that it remains silent irrespective of the presence of transcriptional activators. (2) As somatic differentiation proceeds, lineage-inappropriate genes shift progressively and irreversibly from competent to occluded state, thus restricting cell fate. (3) During reproduction, global deocclusion occurs in the germline and/or early zygotic cells to reset the genome to the competent state. Monoallelic silencing such as X inactivation and imprinting is a clear example of occlusion. Here, the inactive state of the silent alleles can be causally attributed to cis (as opposed to trans) mechanisms given the presence of corresponding active alleles within the same trans environment of the cell. It was unclear, however, whether there are also many genes for which both alleles are occluded. We showed this to be the case using a cell fusion assay. Specifically, we fused two cell types and searched for genes with silent copies in one fusion partner but active copies in the other partner. The active copies served as a positive control for the presence of a transcriptionally supportive milieu, much like the active alleles of monoallelically silenced genes. With this control, the silent copies are identified as being occluded. In the last few years, our lab has accumulated a substantial body of evidence supporting key predictions of the gene occlusion model in mammalian systems. We showed that occlusion is a prevalent phenomenon affecting a large number of genes in a variety of somatic cell types, including both terminally differentiated cells and somatic stem cells. We found that occluded genes in a given cell type include many master regulators of alternative lineages. We established a mechanistic link between DNA methylation and the maintenance of occlusion for at least some occluded genes, and showed that a variety of well-studied chromatin marks are likely not involved in occlusion. We uncovered functional evidence for a critical requirement of occlusion in cell fate restriction. Finally, we showed that embryonic stem cells are fundamentally distinct from somatic cells in that they have the capacity for genome-wide deocclusion. Collectively, these data establish the gene occlusion model as a simple and coherent conceptual framework for studying how the restriction of cell fate is brought about during development, erased during reproduction, and possibly subverted in disease. Currently, we are continuing to study several aspects of the gene occlusion model. First, we are investigating the biochemical mechanism underlying the maintenance of occlusion in somatic cells. Second, we are probing the mechanism by which de novo occlusion is established during differentiation. Third, we are exploring the implications of gene occlusion in a variety of biological processes including stem cell differentiation, induction of iPS cells, cancer and aging.
Biosciences Graduate Program Association
Publications

  1. Lahn BT. Social dominance hierarchy: toward a genetic and evolutionary understanding. Cell Res. 2020 Jul; 30(7):560-561. View in: PubMed

  2. Aaker JD, Elbaz B, Wu Y, Looney TJ, Zhang L, Lahn BT, Popko B. Transcriptional Fingerprint of Hypomyelination in Zfp191null and Shiverer (Mbpshi) Mice. ASN Neuro. 2016 Oct; 8(5). View in: PubMed

  3. Ke Q, Li W, Lai X, Chen H, Huang L, Kang Z, Li K, Ren J, Lin X, Zheng H, Huang W, Ma Y, Xu D, Chen Z, Song X, Lin X, Zhuang M, Wang T, Zhuang F, Xi J, Mao FF, Xia H, Lahn BT, Zhou Q, Yang S, Xiang AP. TALEN-based generation of a cynomolgus monkey disease model for human microcephaly. Cell Res. 2016 09; 26(9):1048-61. View in: PubMed

  4. Du X, Yang XH, Wu YF, Liang J, Zhang J, Huang ZC, Zhu ZP, Lin W, Zou MX, Wen JY, Wu SJ, Guo R, Zhang XM, Lahn BT, He F, Xiang AP. Distribution of the cytoskeletal protein, Nestin, in acute leukemia. Biotech Histochem. 2015 Jul; 90(5):384-94. View in: PubMed

  5. Jiang MH, Li G, Liu J, Liu L, Wu B, Huang W, He W, Deng C, Wang D, Li C, Lahn BT, Shi C, Xiang AP. Nestin(+) kidney resident mesenchymal stem cells for the treatment of acute kidney ischemia injury. Biomaterials. 2015 May; 50:56-66. View in: PubMed

  6. Jiang MH, Cai B, Tuo Y, Wang J, Zang ZJ, Tu X, Gao Y, Su Z, Li W, Li G, Zhang M, Jiao J, Wan Z, Deng C, Lahn BT, Xiang AP. Characterization of Nestin-positive stem Leydig cells as a potential source for the treatment of testicular Leydig cell dysfunction. Cell Res. 2014 Dec; 24(12):1466-85. View in: PubMed

  7. Di CG, Xiang AP, Jia L, Liu JF, Lahn BT, Ma BF. Involvement of extracellular factors in maintaining self-renewal of neural stem cell by nestin. Neuroreport. 2014 Jul 09; 25(10):782-7. View in: PubMed

  8. Madzo J, Liu H, Rodriguez A, Vasanthakumar A, Sundaravel S, Caces DBD, Looney TJ, Zhang L, Lepore JB, Macrae T, Duszynski R, Shih AH, Song CX, Yu M, Yu Y, Grossman R, Raumann B, Verma A, He C, Levine RL, Lavelle D, Lahn BT, Wickrema A, Godley LA. Hydroxymethylation at gene regulatory regions directs stem/early progenitor cell commitment during erythropoiesis. Cell Rep. 2014 Jan 16; 6(1):231-244. View in: PubMed

  9. Looney TJ, Zhang L, Chen CH, Lee JH, Chari S, Mao FF, Pelizzola M, Zhang L, Lister R, Baker SW, Fernandes CJ, Gaetz J, Foshay KM, Clift KL, Zhang Z, Li WQ, Vallender EJ, Wagner U, Qin JY, Michelini KJ, Bugarija B, Park D, Aryee E, Stricker T, Zhou J, White KP, Ren B, Schroth GP, Ecker JR, Xiang AP, Lahn BT. Systematic mapping of occluded genes by cell fusion reveals prevalence and stability of cis-mediated silencing in somatic cells. Genome Res. 2014 Feb; 24(2):267-80. View in: PubMed

  10. Chen F, Cai B, Gao Y, Yuan X, Cheng F, Wang T, Jiang M, Zhou Y, Lahn BT, Li W, Xiang AP. Suicide gene-mediated ablation of tumor-initiating mouse pluripotent stem cells. Biomaterials. 2013 Feb; 34(6):1701-11. View in: PubMed

  11. Ostler KR, Yang Q, Looney TJ, Zhang L, Vasanthakumar A, Tian Y, Kocherginsky M, Raimondi SL, DeMaio JG, Salwen HR, Gu S, Chlenski A, Naranjo A, Gill A, Peddinti R, Lahn BT, Cohn SL, Godley LA. Truncated DNMT3B isoform DNMT3B7 suppresses growth, induces differentiation, and alters DNA methylation in human neuroblastoma. Cancer Res. 2012 Sep 15; 72(18):4714-23. View in: PubMed

  12. Foshay KM, Looney TJ, Chari S, Mao FF, Lee JH, Zhang L, Fernandes CJ, Baker SW, Clift KL, Gaetz J, Di CG, Xiang AP, Lahn BT. Embryonic stem cells induce pluripotency in somatic cell fusion through biphasic reprogramming. Mol Cell. 2012 Apr 27; 46(2):159-70. View in: PubMed

  13. Cheng F, Ke Q, Chen F, Cai B, Gao Y, Ye C, Wang D, Zhang L, Lahn BT, Li W, Xiang AP. Protecting against wayward human induced pluripotent stem cells with a suicide gene. Biomaterials. 2012 Apr; 33(11):3195-204. View in: PubMed

  14. Gaetz J, Clift KL, Fernandes CJ, Mao FF, Lee JH, Zhang L, Baker SW, Looney TJ, Foshay KM, Yu WH, Xiang AP, Lahn BT. Evidence for a critical role of gene occlusion in cell fate restriction. Cell Res. 2012 May; 22(5):848-58. View in: PubMed

  15. Yu WH, Li FG, Chen XY, Li JT, Wu YH, Huang LH, Wang Z, Li P, Wang T, Lahn BT, Xiang AP. PPAR? suppression inhibits adipogenesis but does not promote osteogenesis of human mesenchymal stem cells. Int J Biochem Cell Biol. 2012 Feb; 44(2):377-84. View in: PubMed

  16. Song CX, Szulwach KE, Fu Y, Dai Q, Yi C, Li X, Li Y, Chen CH, Zhang W, Jian X, Wang J, Zhang L, Looney TJ, Zhang B, Godley LA, Hicks LM, Lahn BT, Jin P, He C. Selective chemical labeling reveals the genome-wide distribution of 5-hydroxymethylcytosine. Nat Biotechnol. 2011 Jan; 29(1):68-72. View in: PubMed

  17. Park D, Xiang AP, Mao FF, Zhang L, Di CG, Liu XM, Shao Y, Ma BF, Lee JH, Ha KS, Walton N, Lahn BT. Nestin is required for the proper self-renewal of neural stem cells. Stem Cells. 2010 Dec; 28(12):2162-71. View in: PubMed

  18. Lahn BT. The "occlusis" model of cell fate restriction. Bioessays. 2011 Jan; 33(1):13-20. View in: PubMed

  19. Qin J, Li WQ, Zhang L, Chen F, Liang WH, Mao FF, Zhang XM, Lahn BT, Yu WH, Xiang AP. A stem cell-based tool for small molecule screening in adipogenesis. PLoS One. 2010 Sep 27; 5(9):e13014. View in: PubMed

  20. Wang T, Mao FF, Lai W, Li W, Yu W, Wang Z, Zhang L, Zhang J, Niu J, Zhang X, Lahn BT, Xiang AP. Multiple mesodermal lineage differentiation of Apodemus sylvaticus embryonic stem cells in vitro. BMC Cell Biol. 2010 Jun 19; 11:42. View in: PubMed

  21. Qin JY, Zhang L, Clift KL, Hulur I, Xiang AP, Ren BZ, Lahn BT. Systematic comparison of constitutive promoters and the doxycycline-inducible promoter. PLoS One. 2010 May 12; 5(5):e10611. View in: PubMed

  22. Li W, Liu C, Qin J, Zhang L, Chen R, Chen J, Yu X, Wu G, Lahn BT, Fu Y, Xiang AP. Efficient genetic modification of cynomolgus monkey embryonic stem cells with lentiviral vectors. Cell Transplant. 2010; 19(9):1181-93. View in: PubMed

  23. Kilian KA, Bugarija B, Lahn BT, Mrksich M. Geometric cues for directing the differentiation of mesenchymal stem cells. Proc Natl Acad Sci U S A. 2010 Mar 16; 107(11):4872-7. View in: PubMed

  24. Chen Z, Wang T, Luo H, Lai Y, Yang X, Li F, Lei Y, Su C, Zhang X, Lahn BT, Xiang AP. Expression of nestin in lymph node metastasis and lymphangiogenesis in non-small cell lung cancer patients. Hum Pathol. 2010 May; 41(5):737-44. View in: PubMed

  25. Chen R, Chen J, Cheng S, Qin J, Li W, Zhang L, Jiao H, Yu X, Zhang X, Lahn BT, Xiang AP. Assessment of embryotoxicity of compounds in cosmetics by the embryonic stem cell test. Toxicol Mech Methods. 2010 Mar; 20(3):112-8. View in: PubMed

  26. Li W, Wang D, Qin J, Liu C, Zhang Q, Zhang X, Yu X, Lahn BT, Mao FF, Xiang AP. Generation of functional hepatocytes from mouse induced pluripotent stem cells. J Cell Physiol. 2010 Mar; 222(3):492-501. View in: PubMed

  27. Lahn BT, Ebenstein L. Let's celebrate human genetic diversity. Nature. 2009 Oct 08; 461(7265):726-8. View in: PubMed

  28. Lee JH, Gaetz J, Bugarija B, Fernandes CJ, Snyder GE, Bush EC, Lahn BT. Chromatin analysis of occluded genes. Hum Mol Genet. 2009 Jul 15; 18(14):2567-74. View in: PubMed

  29. Park D, Xiang AP, Zhang L, Mao FF, Walton NM, Choi SS, Lahn BT. The radial glia antibody RC2 recognizes a protein encoded by Nestin. Biochem Biophys Res Commun. 2009 May 08; 382(3):588-92. View in: PubMed

  30. Ke H, Wang P, Yu W, Liu X, Liu C, Yang F, Mao FF, Zhang L, Zhang X, Lahn BT, Xiang AP. Derivation, characterization and gene modification of cynomolgus monkey mesenchymal stem cells. Differentiation. 2009 Mar; 77(3):256-62. View in: PubMed

  31. Lee JH, Bugarija B, Millan EJ, Walton NM, Gaetz J, Fernandes CJ, Yu WH, Mekel-Bobrov N, Vallender TW, Snyder GE, Xiang AP, Lahn BT. Systematic identification of cis-silenced genes by trans complementation. Hum Mol Genet. 2009 Mar 01; 18(5):835-46. View in: PubMed

  32. Vallender EJ, Mekel-Bobrov N, Lahn BT. Genetic basis of human brain evolution. Trends Neurosci. 2008 Dec; 31(12):637-44. View in: PubMed

  33. Peng Y, Chen Z, Yu W, Zhou Q, Xu L, Mao FF, Huang G, Zhang X, Li S, Lahn BT, Xiang AP. Effects of thymic polypeptides on the thymopoiesis of mouse embryonic stem cells. Cell Biol Int. 2008 Oct; 32(10):1265-71. View in: PubMed

  34. Wang P, Liu XM, Liu XM, Ma BF, Jia L, Wang D, Zhang XM, Yu XB, Lahn BT, Xiang AP. Isolation, characterization and gene modification of fetal neural stem/progenitor cells from cynomolgus monkey. Neuroreport. 2008 Mar 05; 19(4):419-24. View in: PubMed

  35. Bush EC, Lahn BT. A genome-wide screen for noncoding elements important in primate evolution. BMC Evol Biol. 2008 Jan 23; 8:17. View in: PubMed

  36. Hawks J, Cochran G, Harpending HC, Lahn BT. A genetic legacy from archaic Homo. Trends Genet. 2008 Jan; 24(1):19-23. View in: PubMed

  37. Yu W, Chen Z, Zhang J, Zhang L, Ke H, Huang L, Peng Y, Zhang X, Li S, Lahn BT, Xiang AP. Critical role of phosphoinositide 3-kinase cascade in adipogenesis of human mesenchymal stem cells. Mol Cell Biochem. 2008 Mar; 310(1-2):11-8. View in: PubMed

  38. Xiang AP, Mao FF, Li WQ, Park D, Ma BF, Wang T, Vallender TW, Vallender EJ, Zhang L, Lee J, Waters JA, Zhang XM, Yu XB, Li SN, Lahn BT. Extensive contribution of embryonic stem cells to the development of an evolutionarily divergent host. Hum Mol Genet. 2008 Jan 01; 17(1):27-37. View in: PubMed

  39. Vallender EJ, Lahn BT. Uncovering the mutation-fixation correlation in short lineages. BMC Evol Biol. 2007 Sep 21; 7:168. View in: PubMed

  40. Yang XH, Wu QL, Yu XB, Xu CX, Ma BF, Zhang XM, Li SN, Lahn BT, Xiang AP. Nestin expression in different tumours and its relevance to malignant grade. J Clin Pathol. 2008 Apr; 61(4):467-73. View in: PubMed

  41. Niemann S, Landers JE, Churchill MJ, Hosler B, Sapp P, Speed WC, Lahn BT, Kidd KK, Brown RH, Hayashi Y. Motoneuron-specific NR3B gene: no association with ALS and evidence for a common null allele. Neurology. 2008 Feb 26; 70(9):666-76. View in: PubMed

  42. Zhang AX, Yu WH, Ma BF, Yu XB, Mao FF, Liu W, Zhang JQ, Zhang XM, Li SN, Li MT, Lahn BT, Xiang AP. Proteomic identification of differently expressed proteins responsible for osteoblast differentiation from human mesenchymal stem cells. Mol Cell Biochem. 2007 Oct; 304(1-2):167-79. View in: PubMed

  43. Ma BF, Liu XM, Zhang AX, Wang P, Zhang XM, Li SN, Lahn BT, Xiang AP. Mathematical models for the proliferation of neural stem/progenitor cells in clonogenic culture. Rejuvenation Res. 2007 Jun; 10(2):205-14. View in: PubMed

  44. Huang G, Li WQ, Chen R, Chen ZG, Zhang XM, Mao FX, Huang SL, Li SN, Lahn BT, Xiang AP. Establishment and characterization of two new human embryonic stem cell lines, SYSU-1 and SYSU-2. Chin Med J (Engl). 2007 Apr 05; 120(7):589-94. View in: PubMed

  45. Evolutionary and biomedical insights from the rhesus macaque genome. Science. 2007 Apr 13; 316(5822):222-34. View in: PubMed

  46. Mekel-Bobrov N, Posthuma D, Gilbert SL, Lind P, Gosso MF, Luciano M, Harris SE, Bates TC, Polderman TJ, Whalley LJ, Fox H, Starr JM, Evans PD, Montgomery GW, Fernandes C, Heutink P, Martin NG, Boomsma DI, Deary IJ, Wright MJ, de Geus EJ, Lahn BT. The ongoing adaptive evolution of ASPM and Microcephalin is not explained by increased intelligence. Hum Mol Genet. 2007 Mar 15; 16(6):600-8. View in: PubMed

  47. Mekel-Bobrov N, Lahn BT. What makes us human: revisiting an age-old question in the genomic era. J Biomed Discov Collab. 2006 Nov 29; 1:18. View in: PubMed

  48. Vallender EJ, Lahn BT. Multiple independent origins of sex chromosomes in amniotes. Proc Natl Acad Sci U S A. 2006 Nov 28; 103(48):18031-2. View in: PubMed

  49. Evans PD, Mekel-Bobrov N, Vallender EJ, Hudson RR, Lahn BT. Evidence that the adaptive allele of the brain size gene microcephalin introgressed into Homo sapiens from an archaic Homo lineage. Proc Natl Acad Sci U S A. 2006 Nov 28; 103(48):18178-83. View in: PubMed

  50. Bush EC, Lahn BT. The evolution of word composition in metazoan promoter sequence. PLoS Comput Biol. 2006 Nov 03; 2(11):e150. View in: PubMed

  51. Vallender TW, Lahn BT. Improved DNA methylation analysis via enrichment of demethylated cells expressing an X-inactivated transgene. Biotechniques. 2006 Oct; 41(4):461-6. View in: PubMed

  52. Vallender EJ, Lahn BT. A primate-specific acceleration in the evolution of the caspase-dependent apoptosis pathway. Hum Mol Genet. 2006 Oct 15; 15(20):3034-40. View in: PubMed

  53. Vallender EJ, Paschall JE, Malcom CM, Lahn BT, Wyckoff GJ. SPEED: a molecular-evolution-based database of mammalian orthologous groups. Bioinformatics. 2006 Nov 15; 22(22):2835-7. View in: PubMed

  54. Choi SS, Vallender EJ, Lahn BT. Systematically assessing the influence of 3-dimensional structural context on the molecular evolution of mammalian proteomes. Mol Biol Evol. 2006 Nov; 23(11):2131-3. View in: PubMed

  55. Vallender TW, Lahn BT. Localized methylation in the key regulator gene endothelin-1 is associated with cell type-specific transcriptional silencing. FEBS Lett. 2006 Aug 07; 580(18):4560-6. View in: PubMed

  56. Zhang JQ, Yu XB, Ma BF, Yu WH, Zhang AX, Huang G, Mao FF, Zhang XM, Wang ZC, Li SN, Lahn BT, Xiang AP. Neural differentiation of embryonic stem cells induced by conditioned medium from neural stem cell. Neuroreport. 2006 Jul 17; 17(10):981-6. View in: PubMed

  57. Dorus S, Anderson JR, Vallender EJ, Gilbert SL, Zhang L, Chemnick LG, Ryder OA, Li W, Lahn BT. Sonic Hedgehog, a key development gene, experienced intensified molecular evolution in primates. Hum Mol Genet. 2006 Jul 01; 15(13):2031-7. View in: PubMed

  58. Evans PD, Vallender EJ, Lahn BT. Molecular evolution of the brain size regulator genes CDK5RAP2 and CENPJ. Gene. 2006 Jun 21; 375:75-9. View in: PubMed

  59. Ma BF, Liu XM, Xie XM, Zhang AX, Zhang JQ, Yu WH, Zhang XM, Li SN, Lahn BT, Xiang AP. Slower cycling of nestin-positive cells in neurosphere culture. Neuroreport. 2006 Mar 20; 17(4):377-81. View in: PubMed

  60. Gilbert SL, Zhang L, Forster ML, Anderson JR, Iwase T, Soliven B, Donahue LR, Sweet HO, Bronson RT, Davisson MT, Wollmann RL, Lahn BT. Trak1 mutation disrupts GABA(A) receptor homeostasis in hypertonic mice. Nat Genet. 2006 Feb; 38(2):245-50. View in: PubMed

  61. Bush EC, Lahn BT. Selective constraint on noncoding regions of hominid genomes. PLoS Comput Biol. 2005 Dec; 1(7):e73. View in: PubMed

  62. Bussell JJ, Pearson NM, Kanda R, Filatov DA, Lahn BT. Human polymorphism and human-chimpanzee divergence in pseudoautosomal region correlate with local recombination rate. Gene. 2006 Mar 01; 368:94-100. View in: PubMed

  63. Choi SS, Bush EC, Lahn BT. Different classes of tissue-specific genes show different levels of noncoding conservation. Genomics. 2006 Mar; 87(3):433-6. View in: PubMed

  64. Choi SS, Li W, Lahn BT. Robust signals of coevolution of interacting residues in mammalian proteomes identified by phylogeny-aided structural analysis. Nat Genet. 2005 Dec; 37(12):1367-71. View in: PubMed

  65. Mekel-Bobrov N, Gilbert SL, Evans PD, Vallender EJ, Anderson JR, Hudson RR, Tishkoff SA, Lahn BT. Ongoing adaptive evolution of ASPM, a brain size determinant in Homo sapiens. Science. 2005 Sep 09; 309(5741):1720-2. View in: PubMed

  66. Evans PD, Gilbert SL, Mekel-Bobrov N, Vallender EJ, Anderson JR, Vaez-Azizi LM, Tishkoff SA, Hudson RR, Lahn BT. Microcephalin, a gene regulating brain size, continues to evolve adaptively in humans. Science. 2005 Sep 09; 309(5741):1717-20. View in: PubMed

  67. Gilbert SL, Dobyns WB, Lahn BT. Genetic links between brain development and brain evolution. Nat Rev Genet. 2005 Jul; 6(7):581-90. View in: PubMed

  68. Wyckoff GJ, Malcom CM, Vallender EJ, Lahn BT. A highly unexpected strong correlation between fixation probability of nonsynonymous mutations and mutation rate. Trends Genet. 2005 Jul; 21(7):381-5. View in: PubMed

  69. Vallender EJ, Pearson NM, Lahn BT. The X chromosome: not just her brother's keeper. Nat Genet. 2005 Apr; 37(4):343-5. View in: PubMed

  70. Gilbert SL, Ozdag F, Ulas UH, Dobyns WB, Lahn BT. Hereditary hyperekplexia caused by novel mutations of GLRA1 in Turkish families. Mol Diagn. 2004; 8(3):151-5. View in: PubMed

  71. Dorus S, Vallender EJ, Evans PD, Anderson JR, Gilbert SL, Mahowald M, Wyckoff GJ, Malcom CM, Lahn BT. Accelerated evolution of nervous system genes in the origin of Homo sapiens. Cell. 2004 Dec 29; 119(7):1027-40. View in: PubMed

  72. Dorus S, Evans PD, Wyckoff GJ, Choi SS, Lahn BT. Rate of molecular evolution of the seminal protein gene SEMG2 correlates with levels of female promiscuity. Nat Genet. 2004 Dec; 36(12):1326-9. View in: PubMed

  73. Vallender EJ, Lahn BT. Effects of chromosomal rearrangements on human-chimpanzee molecular evolution. Genomics. 2004 Oct; 84(4):757-61. View in: PubMed

  74. Vallender EJ, Lahn BT. Positive selection on the human genome. Hum Mol Genet. 2004 Oct 01; 13 Spec No 2:R245-54. View in: PubMed

  75. Wong A, Vallender EJ, Heretis K, Ilkin Y, Lahn BT, Martin CL, Ledbetter DH. Diverse fates of paralogs following segmental duplication of telomeric genes. Genomics. 2004 Aug; 84(2):239-47. View in: PubMed

  76. Evans PD, Anderson JR, Vallender EJ, Choi SS, Lahn BT. Reconstructing the evolutionary history of microcephalin, a gene controlling human brain size. Hum Mol Genet. 2004 Jun 01; 13(11):1139-45. View in: PubMed

  77. Vallender EJ, Lahn BT. How mammalian sex chromosomes acquired their peculiar gene content. Bioessays. 2004 Feb; 26(2):159-69. View in: PubMed

  78. Evans PD, Anderson JR, Vallender EJ, Gilbert SL, Malcom CM, Dorus S, Lahn BT. Adaptive evolution of ASPM, a major determinant of cerebral cortical size in humans. Hum Mol Genet. 2004 Mar 01; 13(5):489-94. View in: PubMed

  79. Choi SS, Lahn BT. Adaptive evolution of MRG, a neuron-specific gene family implicated in nociception. Genome Res. 2003 Oct; 13(10):2252-9. View in: PubMed

  80. Malcom CM, Wyckoff GJ, Lahn BT. Genic mutation rates in mammals: local similarity, chromosomal heterogeneity, and X-versus-autosome disparity. Mol Biol Evol. 2003 Oct; 20(10):1633-41. View in: PubMed

  81. Dorus S, Gilbert SL, Forster ML, Barndt RJ, Lahn BT. The CDY-related gene family: coordinated evolution in copy number, expression profile and protein sequence. Hum Mol Genet. 2003 Jul 15; 12(14):1643-50. View in: PubMed

  82. Lahn BT, Tang ZL, Zhou J, Barndt RJ, Parvinen M, Allis CD, Page DC. Previously uncharacterized histone acetyltransferases implicated in mammalian spermatogenesis. Proc Natl Acad Sci U S A. 2002 Jun 25; 99(13):8707-12. View in: PubMed

  83. Honarpour N, Gilbert SL, Lahn BT, Wang X, Herz J. Apaf-1 deficiency and neural tube closure defects are found in fog mice. Proc Natl Acad Sci U S A. 2001 Aug 14; 98(17):9683-7. View in: PubMed

  84. Lahn BT, Pearson NM, Jegalian K. The human Y chromosome, in the light of evolution. Nat Rev Genet. 2001 Mar; 2(3):207-16. View in: PubMed

  85. Lahn BT, Page DC. A human sex-chromosomal gene family expressed in male germ cells and encoding variably charged proteins. Hum Mol Genet. 2000 Jan 22; 9(2):311-9. View in: PubMed

  86. Lahn BT, Page DC. Four evolutionary strata on the human X chromosome. Science. 1999 Oct 29; 286(5441):964-7. View in: PubMed

  87. Lahn BT, Page DC. Retroposition of autosomal mRNA yielded testis-specific gene family on human Y chromosome. Nat Genet. 1999 Apr; 21(4):429-33. View in: PubMed

  88. Lahn BT, Page DC. Functional coherence of the human Y chromosome. Science. 1997 Oct 24; 278(5338):675-80. View in: PubMed

  89. Lahn BT, Ma N, Breg WR, Stratton R, Surti U, Page DC. Xq-Yq interchange resulting in supernormal X-linked gene expression in severely retarded males with 46,XYq- karyotype. Nat Genet. 1994 Nov; 8(3):243-50. View in: PubMed
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