 |
GEN 228 - Spring
2012 Syllabus & Readings.
| January 27, 2012 Focus on Huntington’s Disease
|
Huntington’s Disease
| 2:00 |
Clinical and patient presentation- Dr. H. Diana
Rosas. |
| 3:00 |
Genetics of HD- Dr. James Gusella. |
| 4:00 |
Models and Modifiers of HD- Dr. Marcy MacDonald. |
Basic concepts to be covered:
- Phenotyping
- Genotype – Phenotype correlations
- Dominant mendelian inheritance
- Linkage analysis
- Positional Cloning
- Concept of triplet repeat diseases
- Modeling genetic disease in mice
- Identification of modifier genes
Reading material:
Thompson & Thompson:
- Introduction and Review – Chapters 1 – 4
- Chapter 5: Patterns of Single-Gene Inheritance
- Chapter 8: pp.111 -131, Mapping Human Genes by Linkage Analysis
- Chapter 12: pp. 236-242, Triplet Repeat Disorders: Unstable,
Dynamic Mutations
- Clinical Case Study-Huntington’s Disease (blue pages)
Papers:
The Huntington’s Disease Collaborative Research Group. 1993.
A Novel Gene Containing a Trinucleotide Repeat That Is Expanded
and Unstable on Huntington’s Disease Chromosomes, Cell, 72:
971-983. Click
here for PDF
James F Gusella and Marcy E MacDonald. Huntington’s disease:
the case for genetic modifiers, Genome Medicine, 2009, 1:80.
Click here for PDF
H. Diana Rosas, David H. Salat, Stephanie Y Lee, Alexandra K. Zaleta,
Vasanth Pappu, Bruce Fischl, Doug Greve, Nathanael Hevelones and
Steven M. Herschl. Cerebral cortex and the clinical expression of
Huntington’s disease: complexity and heterogeneity. Brain
(2008), 131, 1057-1068. Click
here for PDF
Jean Paul G. Vonsattel. Huntington disease models and human neuropathology:
similarities and differences. Acta Neuropathol (2008) 115:55-69.
Click
here for PDF
|
| February 3, 2012 Focus on Cystic Fibrosis |
Cystic Fibrosis
| 2:00 |
Introduction to clinical and genetic aspects of
CF - Drs. Leonard Sicilian and Sam Moskowitz. |
| 2:40 |
Break |
| 2:45 |
CF patient presentation – Dr. Leonard Sicilian |
| 3:25 |
Break |
| 3:35 |
Genetic and environmental factors that modify CF phenotypes
- Dr. Sam Moskowitz. |
| 4:15 |
Break |
| 4:20 |
Novel therapies that target specific CFTR alleles - Dr. Sam
Moskowitz. |
Basic concepts to be covered:
- Autosomal recessive mendelian inheritance
- Pleiotropic effects of single-gene disorders
- Genotype – phenotype correlations
- Identification of modifier genes
- Allele-specific therapeutics
Papers:
Moskowitz SM, Chmiel JF, Sternen DL, Cheng E, Gibson RL, Marshall
SG, Cutting GR. Clinical practice and genetic counseling for cystic
fibrosis and CFTR-related disorders. Genet Med 2008;10:851-868.
Click
here for PDF.
Drumm ML, Konstan MW, Schluchter MD, Handler A, Pace R, Zou F, Zariwala
M, Fargo D, Xu A, Dunn JM, Darrah RJ, Dorfman R, Sandford AJ, Corey
M, Zielenski J, Durie P, Goddard K, Yankaskas JR, Wright FA, Knowles
MR. Genetic modifiers of lung disease in cystic fibrosis. N Engl
J Med 2005;353:1443-1453. Click
here for PDF.
Bartlett JR, Friedman KJ, Ling SC, Pace RG, Bell SC, Bourke B, Castaldo
G, Castellani C, Cipolli M, Colombo C, Colombo JL, Debray D, Fernandez
A, Lacaille F, Macek M, Jr., Rowland M, Salvatore F, Taylor CJ,
Wainwright C, Wilschanski M, Zemkova D, Hannah WB, Phillips MJ,
Corey M, Zielenski J, Dorfman R, Wang Y, Zou F, Silverman LM, Drumm
ML, Wright FA, Lange EM, Durie PR, Knowles MR. Genetic modifiers
of liver disease in cystic fibrosis. Jama 2009;302:1076-1083. Click
here for PDF.
Accurso FJ, Rowe SM, Clancy JP, Boyle MP, Dunitz JM, Durie PR, Sagel
SD, Hornick DB, Konstan MW, Donaldson SH, Moss RB, Pilewski JM,
Rubenstein RC, Uluer AZ, Aitken ML, Freedman SD, Rose LM, Mayer-Hamblett
N, Dong Q, Zha J, Stone AJ, Olson ER, Ordonez CL, Campbell PW, Ashlock
MA, Ramsey BW. Effect of VX-770 in persons with cystic fibrosis
and the G551D-CFTR mutation. N Engl J Med 2010; 363:1991-2003. (Also
see editorial: Welsh MJ. Targeting the basic defect in cystic fibrosis.
N Engl J Med 2010; 363:2056-2057). Click
here for PDF. Click
here for second PDF.
Pedemonte N, Lukacs GL, Du K, Caci E, Zegarra-Moran O, Galietta
LJ, Verkman AS. Small-molecule correctors of defective DeltaF508-CFTR
cellular processing identified by high-throughput screening. J Clin
Invest 2005;115:2564-2571. Click
here for PDF.
Kerem E, Hirawat S, Armoni S, Yaakov Y, Shoseyov D, Cohen M, Nissim-Rafinia
M, Blau H, Rivlin J, Aviram M, Elfring GL, Northcutt VJ, Miller
LL, Kerem B, Wilschanski M. Effectiveness of PTC124 treatment of
cystic fibrosis caused by nonsense mutations: a prospective phase
II trial. Lancet 2008;372:719-727. Click
here for PDF.
Optional Reading Material:
Rommens JM, Iannuzzi MC, Kerem B-S, Drumm ML, Melmer G, Dean M,
Rozmahel R, Cole JL, Kennedy D, Hidaka N, Zsiga M, Buchwald M, Riordan
JR, Tsui L-C, Collins FS. Identification of the cystic fibrosis
gene: chromosome walking and jumping. Science 1989;245:1059-1065.
Click
here for PDF.
Riordan JR, Rommens JM, Kerem B-S, Alon N, Rozmahel R, Grzelczak
Z, Zielenski J, Lok S, Plavsic N, Chou J-L, Drumm ML, Iannuzzi MC,
Collins FS, Tsui L-C. Identification of the cystic fibrosis gene:
cloning and characterization of complementary DNA. Science 1989;245:1066-1073.
Click
here for PDF.
Kerem B-S, Rommens JM, Buchanan JA, Markiewicz D, Cox TK, Chakravarti
A, Buchwald M, Tsui L-C. Identification of the cystic fibrosis gene:
genetic analysis. Science 1989;245:1073-1080. Click
here for PDF.
Griesenbach U, Alton EW. Gene transfer to the lung: lessons learned
from more than 2 decades of CF gene therapy. Adv Drug Deliv Rev
2009;61:128-139. Click
here for PDF.
|
| February 10, 2012 Focus on Alzheimer’s Disease |
Alzheimer’s Disease
| 2:00 |
Clinical and Patient Presentation- Dr. Alireza
Atri |
| 3:00 |
Alzheimer's Disease Genetics - Dr. Rudolph Tanzi |
| 4:00 |
From Genes to Biology - Dr. Rudolph Tanzi |
Basic concepts to be covered:
- AD: signs and symptoms
- Inheritance Patterns of AD
- Single Genes and AD, the Presenilins and APP
- Late-onset AD genetics
- Therapeutics
Reading material:
Thompson & Thompson:
- Case presentation - Alzheimer Disease
Papers:
Tanzi RE, Bertram L. Twenty years of the Alzheimer’s disease
amyloid hypothesis: A genetic perspective. Cell, 2005; 120: 545-555.
Click
here for PDF
Optional reading material:
Bertram L, Lange C, Mullin K, Parkinson M, Hsiao M, Hogan MF, Schjeide
BM, Hooli B, Divito J, Ionita I, Jiang H, Laird N, Moscarillo T,
Ohlsen KL, Elliott K, Wang X, Hu-Lince D, Ryder M, Murphy A, Wagner
SL, Blacker D, Becker KD, Tanzi RE. Genome-wide Association Analysis
Reveals Putative Alzheimer’s Disease Susceptibility Loci in
Addition to APOE. Am J Hum Genet. 2008 Nov;83(5):623-32. Click
here for PDF
Bertram L. Lill CM, Tanzi RE. The genetics of Alzheimer disease:
back to the future. Neuron. 2010 Oct 21; 68(2):270-81. Click
here for PDF
|
| February 17, 2012 Familial Dysautonomia |
Familial Dysautonomia
| 2:00 |
Clinical Presentation - Dr. Felicia Axelrod, Director,
Dysautonomia Center, New York University School of Medicine
and Ms. Sarah Zucker |
| 3:00 |
Discovery of the FD gene - Dr. Susan Slaugenhaupt |
| 4:00 |
Diseases of mRNA splicing - mechanism and treatment - Dr.
Susan Slaugenhaupt |
Basic concepts to be covered:
- Clinical manifestations
- Recessive inheritance
- Linkage analysis and positional cloning
- Haplotypes/power of inbred populations
- Prenatal screening-importance to reduction in disease burden
- mRNA splicing and disease
- Development of treatments for RNA splicing disease
Papers:
Slaugenhaupt SA, Blumenfeld A, Gill SP, Leyne M, Mull J, Cuajungco
MP, Liebert CB, Chadwick B, Idelson M, Reznik L, Robbins CM, Makalowska
I, Brownstein MJ, Krappmann D, Scheidereit C, Maayan C, Axelrod
FB, Gusella JF. Tissue-specific expression of a splicing mutation
in the IKBKAP gene causes familial dysautonomia. Am J Hum
Genet 2001; 68:598-605. Click
here for PDF
Slaugenhaupt SA, Mull J, Leyne M, Cuajungco MP, Gill SP, Hims M,
Quintero F, Axelrod FB, Gusella JF. 2004. Rescue of a human mRNA
splicing defect by the plant cytokinin kinetin. Hum Mol Genet;
13(4):429-36. Click
here for PDF
Hims MM, Ibrahim EC, Leyne M, Mull J, Liu L, Lazaro C, Shetty RS,
Gill S, Gusella JF, Reed R, and Slaugenhaupt SA. 2007. Therapeutic
potential and mechanism of kinetin as a treatment for the human
splicing disease familial dysautonomia. J Mol Med. 85(2):149-61.
Click here
for PDF
Chen YT, Hims MM, Shetty RS, Mull J, Liu L, Leyne M, Slaugenhaupt
SA. Loss of mouse Ikbkap, a subunit of elongator, leads to transcriptional
deficits and embryonic lethality that can be resolved by human IKBKAP.
Mol Cell Biol 2009; 29(3): 736-44. Click
here for PDF
Axelrod FB, Liebes L, Gold-von Simson G, Mendoza S, Mull J, Leyne
M, Norcliffe-Kaufmann L, Kaufmann H, Slaugenhaupt SA. Kinetin Improves
IKBKAP mRNA Splicing in Patients With Familial Dysautonomia. Pediatr
Res 2011; 70: 480-483. Click
here for PDF
Norcliffe-Kaufmann L, Axelrod F, Kaufmann H (2010) Afferent baroreflex
failure in familial dysautonomia. Neurology 75: 1904-11. Click
here for PDF
|
| February 24, 2012 Diseases of the Mitochondrion and Computational
Medicine |
TBA
|
| March 2, 2012 Phakomatosis: Focus on TSC and NF2 |
Phakomatosis: Focus on TSC and NF2
| 2:00 |
Introduction to Phakomatosis and clinical overview
of TSC and NF2
Patient presentations. Dr. Elizabeth Thiele and Dr. Scott Plotkin |
| 3:15 |
Genetics and signaling aspects of TSC and NF2. Dr. Vijaya
Ramesh |
| 4:00 |
Clinical translation. Dr. Thiele and Dr. Plotkin |
Basic concepts to be covered:
- Diagnostic criteria for TSC
- Clinical manifestation of TSC
- Diagnostic criteria for NF2
- Clinical manifestation of NF2
- TSC1 and TSC2 genes and protein
- Mutations, genotype-phenotype correlation
- Regulation of mTOR signaling by TSC1-TSC2 complex
- NF2 gene and protein
- Challenges in correlating NF2 protein function with the disease
- Regulation of mTORC1 signaling by NF2
Clinical Translation:
- Correlation between genotype and cognitive phenotype
- Determinants of autistic features in patients with TSC and NF1
- Emerging treatments for NF2-related hearing loss
- Assisted reproduction in NF2 and TSC
Papers:
Tuberous Sclerosis – a seminar. Curatolo P, Bombardieri R,
Jozwiak S. Lancet 2008; 372: 657–68. Click
here for PDF
Management of the patient and family with neurofibromatosis 2:
a consensus conference statement. Evans DG, Baser ME, O'Reilly B,
Rowe J, Gleeson M, Saeed S, King A, Huson SM, Kerr R, Thomas N,
Irving R, MacFarlane R, Ferner R, McLeod R, Moffat D, Ramsden R.
Br J Neurosurg. 2005 Feb;19(1):5-12. Click
here for PDF
Guertin DA and Sabatini DM. Defining the role of mTOR in cancer.
Cancer Cell. 2007 12:9-22. Click
here for PDF
Huang J and Manning BD. The TSC1-TSC2 complex: a molecular switchboard
controlling cell growth. Biochem J. 2008 412: 179-190. Click
here for PDF
McClatchey AI and Fehon RG. Merlin and the ERM proteins: Regulators
of receptor distribution and signaling at the cell cortex. Trends
Cell Biol 2009 19: 198-206. Click
here for PDF
Original papers for discussion:
James MF, Han S, Polizzano C, Plotkin S, Maning BD, Stemmer-Rachamimov
AO, Gusella JF and Ramesh V. NF2/merlin is a novel negative regulator
of mTOR complex 1 and activation of mTORC1 is associated with meningioma
and schwannoma growth. Mol Cell Biol. 2009 29: 4250-4261. Click
here for PDF
Hearing improvement after bevacizumab in patients with neurofibromatosis
type 2. Plotkin SR, Stemmer-Rachamimov AO, Barker FG 2nd, Halpin
C, Padera TP, Tyrrell A, Sorensen AG, Jain RK, di Tomaso E. N Engl
J Med. 2009 Jul 23;361(4):358-67. Click
here for PDF
Genotype and cognitive phenotype of patients with tuberous sclerosis
complex. Van Eeghen AM, Black ME, Pulsifer MB, Kwiatkowski DJ and
Thiele EA. Eur J of Hum Genetics 2011, 1–6. Click
here for PDF
|
| March 9, 2012 Grant writing and course paper |
no syllabus for this class
|
| March 16, 2012 The Genetic Basis of Type 2 Diabetes |
TBA
|
| March 23, 2012 Inflammatory Bowel Disease |
Crohn’s Disease
| 2:00 |
Clinical and patient presenation – Dr Ramnik
Xavier |
| 2:45 |
Structure of Variation across the Human Genome – Dr.
Mark Daly |
| 3:45 |
Genetics of Crohn’s Disease – Dr. Daly |
| 4:30 |
Functional Genomics and Crohn’s – Dr. Xavier |
Basic concepts to be covered:
- Haplotype structure of the human genome-history of genetic markers,
measures of linkage disequilibrium
- Recombination in the human genome
- Population stratification
- Structural variation
- Genetics and genomics of Crohn’s disease
Papers:
Khor B, Gardet A, Xavier RJ. Genetics and pathogenesis of inflammatory
bowel
disease. Nature. 2011 Jun 15;474(7351):307-17. doi: 10.1038/nature10209.
Review.
PubMed PMID: 21677747; PubMed Central PMCID: PMC3204665. Click
here for PDF
Optional and classic reading material:
Sachidanandam R, et al. International SNP Map Working Group.
A map of human genome sequence variation containing 1.42 million
single nucleotide polymorphisms. Nature. 2001 Feb 15;409(6822):928-33.
Click
here for PDF
Gabriel SB, et al. The structure of haplotype blocks in the human
genome.
Science. 2002 Jun 21;296(5576):2225-9. Click
here for PDF
Franke A, et al. Genome-wide meta-analysis increases to 71 the
number of confirmed Crohn's disease susceptibility loci. Nature
Genetics 2010 Dec;42(12):1118-25. Click
here for PDF
|
| March 30, 2012 Focus on Schizophrenia and Bipolar Disorder and
Association Study Methodology |
|
TBA
|
| April 6, 2012 Genetics of Blood Lipids and Risk for Myocardial
Infarction |
|
Genetics of Blood Lipids and Risk for
Myocardial Infarction
| 2:00 |
Clinical and Patient Presentation – Drs.
Sekar Kathiresan and Christopher Newton-Cheh |
| 3:00 |
Understanding the inherited basis for blood lipids and myocardial
infarction – Dr. Sekar Kathiresan |
Basic concepts to be covered:
- Intermediate Phenotypes
- Quantitative traits
- Heritability
- Genetic architecture for complex quantitative and dichotomous
traits
- Threshold/liability model for disease
- Pharmacogenetics
- Disease risk prediction incorporating genetic information
Reading Material:
Thompson & Thompson:
Chapter 9. The Genetic Contribution to Disease: Locating and identifying
Disease Genes
Papers:
Cohen JC, Kiss RS, Pertsemlidis A, Marcel YL, McPherson R, Hobbs
HH. Multiple rare alleles contribute to low plasma levels of HDL
cholesterol. Science 2004; 305:869-72. Click
here for PDF
Teslovich TM*, Musunuru K*, Global Lipids Genetics Consortium
Collaborators, Cupples LA*, Sandhu MS*, Ridker PM*, Rader DJ*, van
Duijn CM*, Peltonen L*, Abecasis GR*, Boehnke M*, Kathiresan S*.
Biological, clinical, and population relevance of 95 loci for blood
lipids. Nature 2010;466: 707-713. Click
here for PDF
Musunuru K*, Pirruccello JP*, Do R*, Peloso GM, Guiducci C, Sougnez
C, Garimella KV, Fisher S, Abreu J, Barry AJ, Fennell T, Banks E,
Ambrogio L, Cibulskis K, Kernytsky A, Gonzalez E, Rudzicz N, Engert
JC, DePristo MA, Daly MJ, Cohen JC, Hobbs HH, Altshuler D, Schonfeld
G, Gabriel SB*, Yue P*, Kathiresan S*. Exome sequencing, mutations
in ANGPTL3, and familial combined hypolipidemia. N Engl J Med 2010;
363: 2220-2227. Click
here for PDF
Ripatti S, Tikkanen S, Orho-Melander M, Havulinna AS, Silander K,
Sharma A, Guiducci C, Perola M, Jula A, Sinisalo J, Lokki ML, Nieminen
MS, Melander O, Salomaa V, Peltonen L, Kathiresan S. A multi-locus
genetic risk score and risk for incident coronary heart disease.
Lancet, 2010;376: 1393-1400. Click
here for PDF
Optional and Classic Reading Material:
Brown MS, Goldstein JL. A receptor-mediated pathway for cholesterol
homeostasis. Science. 1986; 232: 34-47. Click
here for PDF
Musunuru K*, Strong A*, Frank-Kamenetsky M, Lee NE, Ahfeldt T,
Sachs KV, Li X, Li H, Kuperwasser N, Ruda VM, Pirruccello JJ, Muchmore
B, Prokunina-Olsson L, Hall JL, Schadt EE, Morales CR, Lund-Katz
S, Phillips MC, Wong J, Cantley W, Racie T, Ejebe KG, Orho-Melander
M, Melander O, Koteliansky V, Fitzgerald K, Krauss RM, Cowan CA,
Kathiresan S* & Rader DJ*. From noncoding variant to phenotype
via SORT1 at the 1p13 cholesterol locus. Nature 2010;466: 714-719.
Click
here for PDF
Kathiresan S, Voight BF, Purcell S, Musunuru K, et al. Genome-wide
association of early-onset myocardial infarction with common single
nucleotide polymorphisms, common copy number variants, and rare
copy number variants. Nat Genet 2009;41: 334-341. Click
here for PDF
|
| April 13, 2012 The Cancer Genome: Focus on Breast Cancer |
The Cancer Genome: Focus on Breast Cancer
| 2:00 |
Introduction – Dr. Sridhar Ramaswamy |
| 2:10 |
Clinical and patient presentation – Dr. Paula Ryan
Inherited Breast Cancer Syndromes – Dr. Paula Ryan |
| 3:00 |
Breast Cancer Genetics, Biology, & Oncology – Dr.
Sridhar Ramaswamy |
| 4:00 |
Paper Discussion – Drs. Ramaswamy and Ryan |
Basic concepts to be covered:
- Core Issues in Cancer Medicine & Biology
- Somatic Mutation & Germline Variants
- Functional Genomics
- Therapeutics
Papers:
Shattuck-Eidens D, McClure M, Simard J, Labrie F, Narod S, Couch
F, Hoskins K, Weber B, Castilla L, Erdos M, et al. A collaborative
survey of 80 mutations in the BRCA1 breast and ovarian cancer susceptibility
gene. Implications for presymptomatic testing and screening. JAMA.
1995 Feb 15;273(7):535-41. Click
here for PDF
FitzGerald MG, MacDonald DJ, Krainer M, Hoover I, O'Neil E, Unsal
H, Silva-Arrieto S, Finkelstein DM, Beer-Romero P, Englert C, Sgroi
DC, Smith BL, Younger JW, Garber JE, Duda RB, Mayzel KA, Isselbacher
KJ, Friend SH, Haber DA. Germ-line BRCA1 mutations in Jewish and
non-Jewish women with early-onset breast cancer. N Engl J Med. 1996
Jan 18;334(3):143-9. Click
here for PDF
van de Vijver MJ, He YD, van't Veer LJ, Dai H, Hart AA, Voskuil
DW, Schreiber GJ, Peterse JL, Roberts C, Marton MJ, Parrish M, Atsma
D, Witteveen A, Glas A, Delahaye L, van der Velde T, Bartelink H,
Rodenhuis S, Rutgers ET, Friend SH, Bernards R. A gene-expression
signature as a predictor of survival in breast cancer.N Engl J Med.
2002 Dec 19;347(25):1999-2009. Click
here for PDF
Farmer et al. Targeting the DNA repair defect in BRCA mutant cells
as a therapeutic strategy. Nature (2005) 434:917. Click
here for PDF
Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber T, Mandelker
D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell
C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar
AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE,
Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE. The Consensus
Coding Sequences of Human Breast and Colorectal Cancers. Science.
2006 Sep 7; [Epub ahead of print]. Click
here for PDF
Easton et al. Genome-wide association study identifies novel breast
cancer susceptibility loci. Nature (2007) 447:1087. Click
here for PDF
Beroukhim R, Mermel CH, Porter D, Wei G, Raychaudhuri S, Donovan
J, Barretina J, Boehm JS, Dobson J, Urashima M, Mc Henry KT, Pinchback
RM, Ligon AH, Cho YJ, Haery L, Greulich H, Reich M, Winckler W,
Lawrence MS, Weir BA, Tanaka KE, Chiang DY, Bass AJ, Loo A, Hoffman
C, Prensner J, Liefeld T, Gao Q, Yecies D, Signoretti S, Maher E,
Kaye FJ, Sasaki H, Tepper JE, Fletcher JA, Tabernero J, Baselga
J, Tsao MS, Demichelis F, Rubin MA, Janne PA, Daly MJ, Nucera C,
Levine RL, Ebert BL, Gabriel S, Rustgi AK, Antonescu CR, Ladanyi
M, Letai A, Garraway LA, Loda M, Beer DG, True LD, Okamoto A, Pomeroy
SL, Singer S, Golub TR, Lander ES, Getz G, Sellers WR, Meyerson
M. The landscape of somatic copy-number alteration across human
cancers. Nature. 2010 Feb 18;463(7283):899-905. PMID: 20164920.
Click here
for PDF
|
| April 20, 2012 Treatment of Genetic Disease |
Treatment of Genetic Disease
| 2:00 |
Clinical and patient presentation - Dr. Christopher
Newton-Cheh |
| 3:00 |
Genetics of blood pressure - Dr. Christopher Newton-Cheh |
| 4:15 |
Review of papers - Ji (2), Newton-Cheh (1) - Dr. Christopher
Newton-Cheh |
Basic concepts to be covered:
- Intermediate phenotypes
- Quantitative traits
- Heritability
- Genetic architecture for complex quantitative and dichotomous
traits
- Continuum from rare variants to common variants
- Translating genetics to individuals and populations
Reading Material:
Thompson & Thompson:
Chapter 9. The Genetic Contribution to Disease: Locating and identifying
Disease Genes
Papers:
Erhet GB et al. Genetic variants in novel pathways influence blood
pressure and cardiovascular disease risk. Nature, October 2011.
Volume 478. Click
here for PDF
Ji W, Foo JN, O'Roak BJ, Zhao H, Larson MG, Simon DB, Newton-Cheh
C, State MW, Levy D, Lifton RP. Rare independent mutations in renal
salt handling genes contribute to blood pressure variation. Nature
Genetics. 2008 May;40(5):592-9. Click
here for PDF
Newton-Cheh C, Larson MG, Ramachandran VS, Levy D, Bloch KD, Surti
A, Guiducci C, Kathiresan S, Benjamin EJ, Struck J, Morgenthaler
NG, Bergmann A, Blankenberg S, Kee F, Nilsson P, Yin X, Peltonen
L, Vartiainen E, Salomaa V, Hirschhorn JN, Melander O, Wang TJ.
Association of Common Variants in NPPA and NPPB with Circulating
Natriuretic Peptides and Blood Pressure. Nature Genetics. 2009;41(3):348-53.
Click here for PDF of article and Click
here for PDF of Supplement
Optional Reading Material:
Gitelman's variant of Bartter's syndrome, inherited hypokalaemic
alkalosis, is caused by mutations in the thiazide-sensitive Na-Cl
cotransporter. Simon DB, Nelson-Williams C, Bia MJ, Ellison D, Karet
FE, Molina AM, Vaara I, Iwata F, Cushner HM, Koolen M, Gainza FJ,
Gitleman HJ, Lifton RP.
Click here for PDF
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