HST.161 | Fall 2007 | Graduate

Molecular Biology and Genetics in Modern Medicine


The calendar below presents reading assignments as preparation for lectures, for short papers and questions, and for problem sets. The reading assignments should be completed prior to the lecture for which they are listed.

1 Mendelian genetics, part 1


Binder, William D., Michael A. Fifer, Mary Etta King, and James R. Stone. “Case 26-2005: A 48-Year-Old Man with Sudden Loss of Consciousness while Jogging.” N Engl J Med 353 (2005): 824-832.

Brown, Robert H., D. Phil, P. Ellen Grant, and Christopher R. Pierson. “Case 35-2006: A Newborn Boy with Hypotonia.” N Engl J Med 355 (2006): 2132-2142.

Walton, David S., Shizuo Mukai, Eric F. Grabowski, John E. Munzenrider, and Thaddeus P. Dryja. “Case 5-2006: An 11-Year-Old Girl with Loss of Vision in the Right Eye.” N Engl J Med 354 (2006): 741-748.

Stoler, Joan M., Natalia T. Leach, and Patricia K. Donahoe. “Case 36-2004: A 23-Day-Old Infant with Hypospadias and Failure to Thrive.” N Engl J Med 351 (2004): 2319-2326.

2 Hypertrophic cardiomyopathy  

Discussion section example

Muscular dystrophies

Blake, Derek J., Andrew Weir, Sarah E. Newey, and Kay E. Davies. “Function and Genetics of Dystrophin and Dystrophin-Related Proteins in Muscle.” Physiol Rev 82 (2002): 291-329.

Watkins, Hugh, Ludwig Thierfelder, Ryuichiro Anan, John Jarcho, Akira Matsumori, William McKenna, J. G. Seidman, and Christine E. Seidman. “Independent Origin of Identical? Cardiac Myosin Heavy-Chain Mutations in Hypertrophic Cardiomyopathy.” Am J Hum Genetics 53 (1993): 1180-1185.

Morita, Hiroyuki, Jonathan Seidman, and Christine E. Seidman. “Genetic Causes of Human Heart Failure.” J Clin Invest 115 (2005): 518-526.

Discussion section

Adler, Elliot, Mark A. Hoon, Ken L. Mueller, Jayaram Chandrashekar, Nicholas J. P. Ryba, and Charles S. Zuker. “A Novel Family of Mammalian Taste Receptors.” Cell 100 (2000): 693-702.

Chandrashekar, Jayaram, Ken L. Mueller, Mark A. Hoon, Elliot Adler, Luxin Feng, Wei Guo, Charles S. Zuker, and Nicholas J. P. Ryba. “T2Rs Function as Bitter Taste Receptors.” Cell 100 (2000): 703-711.

For reading assignment 1

Allamand, Valerie, et al. “A Single Homozygous Point Mutation in a 3’ Untranslated Region Motif of Selenoprotein N mRNA Causes SEPN1-related Myopathy.” EMBO Reports 7 (2006): 450-454.

Hatfield, Dolph L., and Vadim N. Gladyshev. “How Selenium Has Altered Our Understanding of the Genetic Code.” Molec and Cell Bio 22 (2002): 3565-3576.


Moosmann, Bernd, and Christian Behl. “Selenoprotein Synthesis and Side-effects of Statins.” Lancet 363 (2004): 892-894.

Baker, Steven K. “Molecular Clues into the Pathogenesis of Statin-mediated Muscle Toxicity.” Muscle & Nerve 31 (2005): 572-580.

Maron, Barry J. “Sudden Death in Young Athletes.” N Engl J Med 349 (2003): 1064-1075.


Mendelian genetics, part 2

Cystic fibrosis

Discussion section

Welch, Ellen M., et al. “PTC124 Targets Genetic Disorders Caused by Nonsense Mutations.” Nature 447 (2007): 87-93.

Kuzmiak, Holly A., and Lynne E. Maquat. “Applying Nonsense-mediated mRNA Decay Research to the Clinic: Progress and Challenges.” Trends in Molecular Medicine 12 (2006): 306-316.

Problem set 1 reading

Song, Lei, Steven R. DePalma, Maria Kharlap, Andrey G. Zenovich, Allison Cirino, Richard Mitchell, Barbara McDonough, Barry J. Maron, Christine E. Seidman, J. G. Seidman, and Carolyn Y. Ho. “Novel Locus for an Inherited Cardiomyopathy Maps to Chromosome 7.” Circulation 113 (2006): 2186-2192.


Discussion sections


Olivieri, Nancy F. “The β-Thalassemias.” N Engl J Med 341 (1999): 99-109.

Min-Oo, Gundula, and Philippe Gros. “Erythrocyte Variants and the Nature of Their Malaria Protective Effect.” Cellular Microbiology 7 (2005): 753-763.


Mechanisms of mutation



Discussion sections

Mithochondrial disorders

Discussion section

Nachman, Michael W., and Susan L. Crowell. “Estimate of the Mutation Rate per Nucleotide in Humans.” Genetics 156 (2000): 297-304.

Crow, James F. “The Origins, Patterns and Implications of Human Spontaneous Mutation.” Nature Reviews Genetics 1 (2000): 40-47.


Chromosomes, part 1

Prenatal diagnostics

For reading assignment 2

Watkins, Hugh, Ludwig Thierfelder, Ryuichiro Anan, John Jarcho, Akira Matsumori, William McKenna, J. G. Seidman, and Christine E. Seidman. “Independent Origin of Identical? Cardiac Myosin Heavy-Chain Mutations in Hypertrophic Cardiomyopathy.” Am J Hum Genetics 53 (1993): 1180-1185.

Koenig, M., et al. “The Molecular Basis for Duchenne versus Becker Muscular Dystrophy: Correlation of Severity with Type of Deletion.” Am J Hum Genet 45 (1989): 498-506.

Liebhaber, S. A., E.-U. Griese, I. Weiss, F. E. Cash, H. Ayyub, D. R. Higgs, and J. Horst. “Inactivation of Human α-globin Gene Expression by a de novo Deletion Located Upstream of the α-globin Gene Cluster.” PNAS 87 (1990): 9431-9435.

9 Discussion sections

Discussion section

Sebat, Jonathan, et al. “Strong Associations of De Novo Copy Number Mutations with Autism.” Science 316 (2007): 445-449.

Iafrate, A. John, Lars Feuk, Miguel N. Rivera, Marc L. Listewnik, Patricia K. Donahoe, Ying Qi, Stephen W. Scherer, and Charles Lee. “Detection of Large-scale Variation in the Human Genome.” Nature Genetics 36 (2004): 949-951.

OMIM: Autism

Problem set 2 reading

Crow, James F. “Felix Bernstein and the First Human Marker Locus.” Genetics 133 (1993): 4-7.


William’s syndrome

Chromosomes, part 2


Discussion sections

Newborn screening



Genetic deafness

Discussion section

Tsakiri, Kalliopi D., et al. “Adult-onset Pulmonary Fibrosis Caused by Mutations in Telomerase.” PNAS 104 (2007): 7552-7557.

Molecular Biology of The Cell

For reading assignment 3

Stamm, Christof, Ingeborg Friehs, Siew Yen Ho, Adrian M. Moran, Richard A. Jonas, and Pedro J. del Nido. “Review: Congenital Supravalvar Aortic Stenosis: A Simple Lesion?” European Journal of Cardio-thoracic Surgery 19 (2001): 195-202.

Meyer-Lindenberg, Andreas, Carolyn B. Mervis, and Karen Faith Berman. “Neural Mechanisms in Williams Syndrome: A Unique Window to Genetic Influences on Cognition and Behaviour.” Nature Reviews Neuroscience 7 (2006): 380-393.


Trinucleotide repeats

Huntington’s disease


Discussion sections

Myotonic dystrophy

Discussion section

Herman, David, Kai Jenssen, Ryan Burnett, Elisabetta Soragni, Susan L Perlman, and Joel M. Gottesfeld. “Histone Deacetylase Inhibitors Reverse Gene Silencing in Friedreich’s Ataxia.” Nature Chemical Biology 2 (2006): 551-558.

Puccio, Helene, and Michel Koenig. “Friedreich Ataxia: A Paradigm for Mitochondrial Diseases.” Current Opinion in Genetics and Development 12 (2202): 272-277.

15 Epigenetics/imprinting/X-inactivation Hydatiform Mole

Discussion sections

Rett syndrome

Discussion section

Bacher, Christian P., Michele Guggiari, Benedikt Brors, Sandrine Augui, Philippe Clerc, Philip Avner, Roland Eils, and Edith Heard. “Transient Colocalization of X-inactivation Centres Accompanies the Initiation of X Inactivation.” Nature Cell Biology 8 (2006): 293-299.

Xu, Na, Chia-Lun Tsai, and Jeannie T. Lee. “Transient Homologous Chromosome Pairing Marks the Onset of X Inactivation.” Science 311 (2006): 1149-1152.

17 Facioscapulohumeral Dystrophy (FSHD)

For reading assignment 4

Orr, Harry T., and Huda Y. Zoghbi. “Trinucleotide Repeat Disorders.” Annu Rev Neurosci 30 (2007): 575-621.


Ranum, Laura P. W., and Thomas A. Cooper. “RNA-Mediated Neuromuscular Disorders.” Annu Rev Neurosci 29 (2006): 259-277.

Mirkin, Sergei M. “DNA Structures, Repeat Expansions and Human Hereditary Disorders.” Current Opinion in Structural Biology 16 (2006): 351-358.

Penagarikano, Olga, Jennifer G. Mulle, and Stephen T. Warren. “The Pathophysiology of Fragile X Syndrome.” Annu Rev Genomics Hum Genet 8 (2007): 109-129.

Butler, Rachel, and Gillian P. Bates. “Histone Deacetylase Inhibitors as Therapeutics for Polyglutamine Disorders.” Nature Reviews Neuroscience 7 (2006): 784-796.

Imbert, Georges, Christine Kretz, Keith Johnson, and Jean-Louis Mandel. “Original of the Expansion Mutation in Myotonic Dystrophy.” Nature Genetics 4 (1993): 72-76.

Bachinski, Linda L., et al. “Confirmation of the Type 2 Myotonic Dystrophy (CCTG)n Expansion Mutation in Patients with Proximal Myotonic Myopathy/Proximal Myotonic Dystrophy of Different European Origins: A Single Shared Haplotype Indicates an Ancestral Founder Effect.” Am J Hum Genet 73 (2003): 835-848.

Martorell, L., J. Gamez, M. L. Cayuela, F. K. Gould, J. P. McAbney, T. Ashizawa, D. G. Monckton, and M. Baiget. “Germline Mutational Dynamics in Myotonic Dystrophy Type 1 Males: Allele Length and Age Effects.” Neurology 62 (2004): 269-274.

Kanadia, Rahul N., et al. “A Muscleblind Knockout Model for Myotonic Dystrophy.” Science 302 (2003): 1978-1980.

Manley, Kevin, Thomas L. Shirley, Lorraine Flaherty, and Anne Messer. “Msh2 Deficiency Prevents in Vivo Somatic Instability of the CAG Repeat in Huntington Disease Transgenic Mice.” Nature Genetics 23 (1999): 471-473.

Lin, Xiaoyan, et al. “Failure of MBNL1-dependent Post-natal Splicing Transitions in Myotonic Dystrophy.” Human Molecular Genetics 15 (2006): 2087-2097.

McBride, Sean M. J., et al. “Pharmacological Rescue of Synaptic Plasticity, Courtship Behavior, and Mushroom Body Defects in a Drosophila Model of Fragile X Syndrome.” Neuron 45 (2005): 753-764.

Hockly, Emma, et al. “Suberoylanilide Hydroxamic Acid, a Histone Deacetylase Inhibitor, Ameliorates Motor Deficits in a Mouse Model of Huntington’s Disease.” PNAS 100 (2003): 2041-2046.


Discussion sections


Discussion section

Lemmers, Richard J. L. F., et al. “Specific Sequence Variations within the 4q35 Region Are Associated with Facioscapulohumeral Muscular Dystrophy.” Am J Hum Genet 81 (2007): 884-894.

Van der Maarel, Silvere M., and Rune R. Frants. “The D4Z4 Repeat-Mediated Pathogenesis for Facioscapulohumeral Muscular Dystrophy.” Am J Hum Genet 76 (2005): 375-386.

Lemmers, Richard J. L. F., et al. “Facioscapulohumeral Muscular Dystrophy is Uniquely Associated With One of the Two Variants of the 4q Subtelomere.” Nature Genetics 32 (2002): 235-236.

19 Colon cancer

For reading assignment 5

Buiting, Karin, et al. “Epimutations in Prader-Willi and Angelman Syndromes: A Molecular Study of 136 Patients with an Imprinting Defect.” Am J Hum Genet 72 (2003): 571-577.

Horsthemke, B., and K. Buiting. “Imprinting Defects on Human Chromosome 15.” Cytogenet Genome Res 113 (2006): 292-299.

Williamson, Sarah L., and John Christodoulou. “Rett Syndrome: New Clinical and Molecular Insights.” Euro J Hum Genet 14 (2006): 896-903.

Reik, Wolf, and Annabelle Lewis. “Co-evolution of X-chromosome Inactivation and Imprinting in Mammals.” Nature Rev Genetics 1, AOP (2005): 1-8.

Robertson, Keith D. “DNA Methylation and Human Disease.” Nature Rev Genetics 6 (2005): 597-610.


Discussion sections


Discussion section

Bell, Daphne W., et al. “Inherited Susceptibility to Lung Cancer may be Associated With the T790M Drug Resistance Mutation in EGFR.” Nature Genetics 37 (2005): 1315-1316.

Engelman, Jeffrey A., et al. “MET Amplification Leads to Gefitinib Resistance in Lung Cancer by Activating ERBB3 Signaling.” Science 316 (2007): 1039-1043.


Complex traits

Hereditary Breast Ovarian Cancer


Genomic and epigenomic studies of human cancers

Gene therapy

Problem set 3 reading

Cavenee, W. K., et al. “Expression of Recessive Alleles by Chromosomal Mechanisms in Retinoblastoma.” Nature 305 (1983): 779-784.

23 RNAi  

Discussion sections


Discussion section

Klein, Robert J. “Complement Factor H Polymorphism in Age-Related Macular Degeneration.” Science 308 (2005): 385-389.