ABOUT THE RESEARCHER

OVERVIEW

  1. Autism and neurodevelopmental genetics: The Yu lab conducts genome-wide and world-wide searches to find the genes that are responsible for autism spectrum disorders (ASDs) and other neurodevelopmental conditions. We have had a particular emphasis on biallelic/recessive mutations (i.e., impacting both copies of a gene) in ASD, and have uncovered a striking enrichment of biallelic gene disruptions in affected individuals, especially in girls. 
  2. Rare diseases and translational genomic medicine: We are passionate about finding ways to bring genomic tools to the bedside to help care for patients with genetic disorders. These projects range from the deployment of genome sequencing in the neonatal intensive care unit to the design and delivery of genome-guided therapeutics for sick children.

BACKGROUND

Dr. Yu completed his undergraduate degree in biochemistry and molecular biology at Harvard College, his M.D. and Ph.D. degree (in Neuroscience) from the University of California at San Francisco, clinical neurology training at Massachusetts General Hospital and Brigham and Women’s Hospital, and a fellowship in neurodevelopmental genetics at MGH and Boston Children’s Hospital. He joined the faculty in the Division of Genetics and Genomics as Instructor in 2010 and Assistant Professor in 2013.

Selected Publications

  1. Jamuar SS, Schmitz-Abe K, D'Gama AM, Drottar M, Chan WM, Peeva M, Servattalab S, Lam AN, Delgado MR, Clegg NJ, Zayed ZA, Dogar MA, Alorainy IA, Jamea AA, Abu-Amero K, Griebel M, Ward W, Lein ES, Markianos K, Barkovich AJ, Robson CD, Grant PE, Bosley TM, Engle EC, Walsh CA, Yu TW. Biallelic mutations in human DCC cause developmental split-brain syndrome. Nat Genet. 2017 Feb 27; PubMed PMID: 28250456.

  2. Berg JS, Agrawal PB, Bailey DB Jr, Beggs AH, Brenner SE, Brower AM, Cakici JA, Ceyhan-Birsoy O, Chan K, Chen F, Currier RJ, Dukhovny D, Green RC, Harris-Wai J, Holm IA, Iglesias B, Joseph G, Kingsmore SF, Koenig BA, Kwok PY, Lantos J, Leeder SJ, Lewis MA, McGuire AL, Milko LV, Mooney SD, Parad RB, Pereira S, Petrikin J, Powell BC, Powell CM, Puck JM, Rehm HL, Risch N, Roche M, Shieh JT, Veeraraghavan N, Watson MS, Willig L, Yu TW, Urv T, Wise AL. Newborn Sequencing in Genomic Medicine and Public Health. Pediatrics. 2017 Feb;139(2)PubMed PMID: 28096516; PubMed Central PMCID: PMC5260149.

  3. Jayaraman D, Kodani A, Gonzalez DM, Mancias JD, Mochida GH, Vagnoni C, Johnson J, Krogan N, Harper JW, Reiter JF, Yu TW, Bae BI, Walsh CA. Microcephaly Proteins Wdr62 and Aspm Define a Mother Centriole Complex Regulating Centriole Biogenesis, Apical Complex, and Cell Fate. Neuron. 2016 Nov 23;92(4):813-828. PubMed PMID: 27974163; PubMed Central PMCID: PMC5199216.

  4. Jamuar SS, Lam AT, Kircher M, D'Gama AM, Wang J, Barry BJ, Zhang X, Hill RS, Partlow JN, Rozzo A, Servattalab S, Mehta BK, Topcu M, Amrom D, Andermann E, Dan B, Parrini E, Guerrini R, Scheffer IE, Berkovic SF, Leventer RJ, Shen Y, Wu BL, Barkovich AJ, Sahin M, Chang BS, Bamshad M, Nickerson DA, Shendure J, Poduri A, Yu TW, Walsh CA. Somatic mutations in cerebral cortical malformations. N Engl J Med. 2014 Aug 21;371(8):733-43. PubMed PMID: 25140959; PubMed Central PMCID: PMC4274952.

  5. De Rubeis S, He X, Goldberg AP, Poultney CS, Samocha K, Cicek AE, Kou Y, Liu L, Fromer M, Walker S, Singh T, Klei L, Kosmicki J, Shih-Chen F, Aleksic B, Biscaldi M, Bolton PF, Brownfeld JM, Cai J, Campbell NG, Carracedo A, Chahrour MH, Chiocchetti AG, Coon H, Crawford EL, Curran SR, Dawson G, Duketis E, Fernandez BA, Gallagher L, Geller E, Guter SJ, Hill RS, Ionita-Laza J, Jimenz Gonzalez P, Kilpinen H, Klauck SM, Kolevzon A, Lee I, Lei I, Lei J, Lehtimäki T, Lin CF, Ma'ayan A, Marshall CR, McInnes AL, Neale B, Owen MJ, Ozaki N, Parellada M, Parr JR, Purcell S, Puura K, Rajagopalan D, Rehnström K, Reichenberg A, Sabo A, Sachse M, Sanders SJ, Schafer C, Schulte-Rüther M, Skuse D, Stevens C, Szatmari P, Tammimies K, Valladares O, Voran A, Li-San W, Weiss LA, Willsey AJ, Yu TW, Yuen RK, Cook EH, Freitag CM, Gill M, Hultman CM, Lehner T, Palotie A, Schellenberg GD, Sklar P, State MW, Sutcliffe JS, Walsh CA, Scherer SW, Zwick ME, Barett JC, Cutler DJ, Roeder K, Devlin B, Daly MJ, Buxbaum JD. Synaptic, transcriptional and chromatin genes disrupted in autism. Nature. 2014 Nov 13;515(7526):209-15. PubMed PMID: 25363760; PubMed Central PMCID: PMC4402723.

  6. Yu TW, Berry-Kravis E. Autism and fragile X syndrome. Semin Neurol. 2014 Jul;34(3):258-65. PubMed PMID: 25192504.

  7. Yu TW, Chahrour MH, Coulter ME, Jiralerspong S, Okamura-Ikeda K, Ataman B, Schmitz-Abe K, Harmin DA, Adli M, Malik AN, D'Gama AM, Lim ET, Sanders SJ, Mochida GH, Partlow JN, Sunu CM, Felie JM, Rodriguez J, Nasir RH, Ware J, Joseph RM, Hill RS, Kwan BY, Al-Saffar M, Mukaddes NM, Hashmi A, Balkhy S, Gascon GG, Hisama FM, LeClair E, Poduri A, Oner O, Al-Saad S, Al-Awadi SA, Bastaki L, Ben-Omran T, Teebi AS, Al-Gazali L, Eapen V, Stevens CR, Rappaport L, Gabriel SB, Markianos K, State MW, Greenberg ME, Taniguchi H, Braverman NE, Morrow EM, Walsh CA. Using whole-exome sequencing to identify inherited causes of autism. Neuron. 2013 Jan 23;77(2):259-73. PubMed PMID: 23352163; PubMed Central PMCID: PMC3694430.

  8. Chahrour MH, Yu TW, Lim ET, Ataman B, Coulter ME, Hill RS, Stevens CR, Schubert CR; ARRA Autism Sequencing Collaboration, Greenberg ME, Gabriel SB, Walsh CA. Whole-exome sequencing and homozygosity analysis implicate depolarization-regulated neuronal genes in autism. PLoS Genet. 2012;8(4):e1002635.

  9. Yu TW, Mochida GH, Tischfield DJ, Sgaier SK, Flores-Sarnat L, Sergi CM, Topçu M, McDonald MT, Barry BJ, Felie JM, Sunu C, Dobyns WB, Folkerth RD, Barkovich AJ, Walsh CA. Mutations in WDR62, encoding a centrosome-associated protein, cause microcephaly with simplified gyri and abnormal cortical architecture. Nat Genet. 2010 Nov;42(11):1015-2

  10. Chang C, Yu TW, Bargmann CI, Tessier-Lavigne M. Inhibition of netrin-mediated axon attraction by a receptor protein tyrosine phosphatase. Science. 2004 Jul 2;305(5680):103-6. PubMed PMID: 15232111.

  11. Gitai Z, Yu TW, Lundquist EA, Tessier-Lavigne M, Bargmann CI. The netrin receptor UNC-40/DCC stimulates axon attraction and outgrowth through enabled and, in parallel, Rac and UNC-115/AbLIM. Neuron. 2003 Jan 9;37(1):53-65. PubMed PMID:  12526772.

  12. Yu TW, Hao JC, Lim W, Tessier-Lavigne M, Bargmann CI. Shared receptors in axon guidance: SAX-3/Robo signals via UNC-34/Enabled and a Netrin-independent UNC-40/DCC function. Nat Neurosci. 2002 Nov;5(11):1147-54. PubMed PMID: 12379860.

  13. Hao JC, Yu TW, Fujisawa K, Culotti JG, Gengyo-Ando K, Mitani S, Moulder G, Barstead R, Tessier-Lavigne M, Bargmann CI. C. elegans slit acts in midline, dorsal-ventral, and anterior-posterior guidance via the SAX-3/Robo receptor. Neuron. 2001 Oct 11;32(1):25-38. PubMed PMID: 11604136.

  14. Parent JM, Yu TW, Leibowitz RT, Geschwind DH, Sloviter RS, Lowenstein DH. Dentate granule cell neurogenesis is increased by seizures and contributes to aberrant network reorganization in the adult rat hippocampus. J Neurosci. 1997 May 15;17(10):3727-38. PubMed PMID: 9133393.

PUBLICATIONS

Publications powered by Harvard Catalyst Profiles

  1. Exome and genome sequencing for pediatric patients with congenital anomalies or intellectual disability: an evidence-based clinical guideline of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2021 Jul 01. View abstract
  2. Discordant results between conventional newborn screening and genomic sequencing in the BabySeq Project. Genet Med. 2021 Jul; 23(7):1372-1375. View abstract
  3. Disruption of RFX family transcription factors causes autism, attention-deficit/hyperactivity disorder, intellectual disability, and dysregulated behavior. Genet Med. 2021 06; 23(6):1028-1040. View abstract
  4. Homozygous deletions implicate non-coding epigenetic marks in Autism spectrum disorder. Sci Rep. 2020 08 20; 10(1):14045. View abstract
  5. Children's rare disease cohorts: an integrative research and clinical genomics initiative. NPJ Genom Med. 2020; 5:29. View abstract
  6. Children's rare disease cohorts: an integrative research and clinical genomics initiative. NPJ Genom Med. 2020 Jul 06; 5(1):29. View abstract
  7. A phenotypically severe, biochemically "silent" case of HIBCH deficiency in a newborn diagnosed by rapid whole exome sequencing and enzymatic testing. Am J Med Genet A. 2020 04; 182(4):780-784. View abstract
  8. Prospective, phenotype-driven selection of critically ill neonates for rapid exome sequencing is associated with high diagnostic yield. Genet Med. 2020 04; 22(4):736-744. View abstract
  9. Patient-Customized Oligonucleotide Therapy for a Rare Genetic Disease. N Engl J Med. 2019 10 24; 381(17):1644-1652. View abstract
  10. De Novo Variants in WDR37 Are Associated with Epilepsy, Colobomas, Dysmorphism, Developmental Delay, Intellectual Disability, and Cerebellar Hypoplasia. Am J Hum Genet. 2019 Sep 05; 105(3):672-674. View abstract
  11. Infant mortality: the contribution of genetic disorders. J Perinatol. 2019 12; 39(12):1611-1619. View abstract
  12. De Novo Variants in WDR37 Are Associated with Epilepsy, Colobomas, Dysmorphism, Developmental Delay, Intellectual Disability, and Cerebellar Hypoplasia. Am J Hum Genet. 2019 08 01; 105(2):413-424. View abstract
  13. Recessive gene disruptions in autism spectrum disorder. Nat Genet. 2019 07; 51(7):1092-1098. View abstract
  14. Unique bioinformatic approach and comprehensive reanalysis improve diagnostic yield of clinical exomes. Eur J Hum Genet. 2019 09; 27(9):1398-1405. View abstract
  15. Interpretation of Genomic Sequencing Results in Healthy and Ill Newborns: Results from the BabySeq Project. Am J Hum Genet. 2019 01 03; 104(1):76-93. View abstract
  16. Parental interest in genomic sequencing of newborns: enrollment experience from the BabySeq Project. Genet Med. 2019 03; 21(3):622-630. View abstract
  17. Reconciling newborn screening and a novel splice variant in BTD associated with partial biotinidase deficiency: a BabySeq Project case report. Cold Spring Harb Mol Case Stud. 2018 08; 4(4). View abstract
  18. The BabySeq project: implementing genomic sequencing in newborns. BMC Pediatr. 2018 07 09; 18(1):225. View abstract
  19. DCC mutation update: Congenital mirror movements, isolated agenesis of the corpus callosum, and developmental split brain syndrome. Hum Mutat. 2018 01; 39(1):23-39. View abstract
  20. Rare variant association test in family-based sequencing studies. Brief Bioinform. 2017 Nov 01; 18(6):954-961. View abstract
  21. Integrated genome and transcriptome sequencing identifies a noncoding mutation in the genome replication factor DONSON as the cause of microcephaly-micromelia syndrome. Genome Res. 2017 08; 27(8):1323-1335. View abstract
  22. Increased Survival and Partly Preserved Cognition in a Patient With ACO2-Related Disease Secondary to a Novel Variant. J Child Neurol. 2017 08; 32(9):840-845. View abstract
  23. Biallelic mutations in human DCC cause developmental split-brain syndrome. Nat Genet. 2017 Apr; 49(4):606-612. View abstract
  24. From Sequence Data to Returnable Results: Ethical Issues in Variant Calling and Interpretation. Genet Test Mol Biomarkers. 2017 Mar; 21(3):178-183. View abstract
  25. Newborn Sequencing in Genomic Medicine and Public Health. Pediatrics. 2017 Feb; 139(2). View abstract
  26. A curated gene list for reporting results of newborn genomic sequencing. Genet Med. 2017 07; 19(7):809-818. View abstract
  27. Microcephaly Proteins Wdr62 and Aspm Define a Mother Centriole Complex Regulating Centriole Biogenesis, Apical Complex, and Cell Fate. Neuron. 2016 Nov 23; 92(4):813-828. View abstract
  28. The sensitivity of exome sequencing in identifying pathogenic mutations for LGMD in the United States. J Hum Genet. 2017 Feb; 62(2):243-252. View abstract
  29. A novel de novo mutation in ATP1A3 and childhood-onset schizophrenia. Cold Spring Harb Mol Case Stud. 2016 Sep; 2(5):a001008. View abstract
  30. BRAT1 mutations present with a spectrum of clinical severity. . 2016 09; 170(9):2265-73. View abstract
  31. Orthogonal NGS for High Throughput Clinical Diagnostics. Sci Rep. 2016 Apr 19; 6:24650. View abstract
  32. Overlapping 16p13.11 deletion and gain of copies variations associated with childhood onset psychosis include genes with mechanistic implications for autism associated pathways: Two case reports. . 2016 May; 170A(5):1165-73. View abstract
  33. Insights into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci. Neuron. 2015 Sep 23; 87(6):1215-1233. View abstract
  34. Centriolar satellites assemble centrosomal microcephaly proteins to recruit CDK2 and promote centriole duplication. Elife. 2015 Aug 22; 4. View abstract
  35. Katanin p80 regulates human cortical development by limiting centriole and cilia number. Neuron. 2014 Dec 17; 84(6):1240-57. View abstract
  36. Synaptic, transcriptional and chromatin genes disrupted in autism. Nature. 2014 Nov 13; 515(7526):209-15. View abstract
  37. A genome-wide association study of autism using the Simons Simplex Collection: Does reducing phenotypic heterogeneity in autism increase genetic homogeneity? Biol Psychiatry. 2015 May 01; 77(9):775-84. View abstract
  38. Autism and fragile X syndrome. Semin Neurol. 2014 Jul; 34(3):258-65. View abstract
  39. Somatic mutations in cerebral cortical malformations. N Engl J Med. 2014 Aug 21; 371(8):733-43. View abstract
  40. POMK mutations disrupt muscle development leading to a spectrum of neuromuscular presentations. Hum Mol Genet. 2014 Nov 01; 23(21):5781-92. View abstract
  41. Modest impact on risk for autism spectrum disorder of rare copy number variants at 15q11.2, specifically breakpoints 1 to 2. Autism Res. 2014 Jun; 7(3):355-62. View abstract
  42. An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge. Genome Biol. 2014 Mar 25; 15(3):R53. View abstract
  43. Mutations in QARS, encoding glutaminyl-tRNA synthetase, cause progressive microcephaly, cerebral-cerebellar atrophy, and intractable seizures. Am J Hum Genet. 2014 Apr 03; 94(4):547-58. View abstract
  44. METTL23, a transcriptional partner of GABPA, is essential for human cognition. Hum Mol Genet. 2014 Jul 01; 23(13):3456-66. View abstract
  45. Identification of KLHL41 Mutations Implicates BTB-Kelch-Mediated Ubiquitination as an Alternate Pathway to Myofibrillar Disruption in Nemaline Myopathy. Am J Hum Genet. 2013 Dec 05; 93(6):1108-17. View abstract
  46. Mutation of KCNJ8 in a patient with Cantú syndrome with unique vascular abnormalities - support for the role of K(ATP) channels in this condition. Eur J Med Genet. 2013 Dec; 56(12):678-82. View abstract
  47. Exome sequencing identifies a novel SMCHD1 mutation in facioscapulohumeral muscular dystrophy 2. Neuromuscul Disord. 2013 Dec; 23(12):975-80. View abstract
  48. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nat Genet. 2013 Sep; 45(9):984-94. View abstract
  49. Cardiac expression of human type 2 iodothyronine deiodinase increases glucose metabolism and protects against doxorubicin-induced cardiac dysfunction in male mice. Endocrinology. 2013 Oct; 154(10):3937-46. View abstract
  50. Adjusting head circumference for covariates in autism: clinical correlates of a highly heritable continuous trait. Biol Psychiatry. 2013 Oct 15; 74(8):576-84. View abstract
  51. Using whole-exome sequencing to identify inherited causes of autism. Neuron. 2013 Jan 23; 77(2):259-73. View abstract
  52. Common genetic variants, acting additively, are a major source of risk for autism. Mol Autism. 2012 Oct 15; 3(1):9. View abstract
  53. Exome sequencing and functional validation in zebrafish identify GTDC2 mutations as a cause of Walker-Warburg syndrome. Am J Hum Genet. 2012 Sep 07; 91(3):541-7. View abstract
  54. Whole-exome sequencing and homozygosity analysis implicate depolarization-regulated neuronal genes in autism. PLoS Genet. 2012; 8(4):e1002635. View abstract
  55. FLNA genomic rearrangements cause periventricular nodular heterotopia. Neurology. 2012 Jan 24; 78(4):269-78. View abstract
  56. Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams syndrome region, are strongly associated with autism. Neuron. 2011 Jun 09; 70(5):863-85. View abstract
  57. Mutations in WDR62, encoding a centrosome-associated protein, cause microcephaly with simplified gyri and abnormal cortical architecture. Nat Genet. 2010 Nov; 42(11):1015-20. View abstract
  58. Education research: A program perspective on learning how to teach. Neurology. 2008 May 06; 70(19):e75-7. View abstract
  59. Thrombotic intracranial aneurysms: classification scheme and management strategies in 68 patients. Neurosurgery. 2005 Mar; 56(3):441-54; discussion 441-54. View abstract
  60. Inhibition of netrin-mediated axon attraction by a receptor protein tyrosine phosphatase. Science. 2004 Jul 02; 305(5680):103-6. View abstract
  61. The netrin receptor UNC-40/DCC stimulates axon attraction and outgrowth through enabled and, in parallel, Rac and UNC-115/AbLIM. Neuron. 2003 Jan 09; 37(1):53-65. View abstract
  62. Shared receptors in axon guidance: SAX-3/Robo signals via UNC-34/Enabled and a Netrin-independent UNC-40/DCC function. Nat Neurosci. 2002 Nov; 5(11):1147-54. View abstract
  63. Dynamic regulation of axon guidance. Nat Neurosci. 2001 Nov; 4 Suppl:1169-76. View abstract
  64. C. elegans slit acts in midline, dorsal-ventral, and anterior-posterior guidance via the SAX-3/Robo receptor. Neuron. 2001 Oct 11; 32(1):25-38. View abstract
  65. Dentate granule cell neurogenesis is increased by seizures and contributes to aberrant network reorganization in the adult rat hippocampus. J Neurosci. 1997 May 15; 17(10):3727-38. View abstract