genetics 202 human genetics -...

Genetics 202 Autumn 2010 ________________________________________________________________________

Genetics 202 Human Genetics

Autumn 2010 Department of Genetics

Stanford University School of Medicine

______________________________________________________________________________ Genetics 202: Human Genetics

GENE 202 – HUMAN GENETICS

AUTUMN QUARTER 2010 TUES/THURS 9-11AM -- LK 130

Lecture#

Day

Date Time Location Topic Instructor Readings: (Young if not specified)

1 Tues 9/28/10 9-11am LK130 Course Overview; Review of Basic Genetics Principles; Chromosomes and Prenatal Genetics

Hudgins and Ormond

Ch 1, Ch 13 (p 243-244) Feero, Guttmacher Collins (2010) NEJM 362:2001-11. Uhlmann and Guttmacher (2008) JAMA. 299(11): 1356-8. ------- Ch 2 and 3; Ch 14 (p 271-276); Manning and Hudgins(2010) Genet Med epub

2 Thurs 9/30 9-11am LK130 Chromosomes and Prenatal Genetics II

Hudgins and Ormond

See above

3 Tues 10/5 9-11am LK130 Single Gene Disorders

Ormond and Hudgins

Ch 4 (p 69-81) ; Ch 7 (p 135-138); Ch 13 (p 244-252)

4 Thurs

10/7 9-10am LK130

Single Gene Disorders II

Ormond and Hudgins

See above

4 Thurs

10/7 10-11am

LK203/4 LK 205/6 LK208 LK209

Study section on Chromosome Disorders

Cherry Manning Chen Taylor

No readings

5 Tues 10/12 9-11am LK130 Cancer Genetics Ford Ch 10; Pollack and Welsh (2010) Am J Clin Oncol epub; Shulman (2010) Obstet Gynecol Clin North Am. 37(1):109-33

6 Thurs 10/14 9-10am LK130 Nonmendelian Bernstein Ch 4 pp 81-88

Modes of Inheritance

Optional: Siegel and Slavotinek (2005) Ped Derm 22:482-7.

6 Thurs 10/14 10-11am

LK203/4 LK 205/6 LK208 LK209

Study section on Single Gene Disorders

Bernstein Kwan Merker Muller

No readings

7 Tues 10/19 9-11am LK 130 Biochemical Genetics

Enns and Schelley

Ch 11; Levy (2009) Pediatr Rev 30;131

8 Thurs 10/21 9-10am LK203/4 LK 205/6 LK208 LK209

Study section on Cancer Genetics

Ladabaum Ford Lebensohn Chun

No readings

Thurs 10/21 10-11am

LK 203/4 Optional review session on Chromosomes and Single Gene Disorders

Hudgins and Ormond

No readings

9 Tues 10/26 9-11am LK130 Genomics and Complex Disorders

Ormond and Hudgins

Ch 6 Manolio 2010. N Engl J Med; 363:166-176 Manolio et al. 2009; Nature. 461(7265):747-53. Pearson and Manolio (2008) JAMA 299:1335.

10 Thurs 10/28 9-10am LK130 Genomics and Complex Disorders II

Hudgins and Ormond

See above

10 Thurs 10/28 10-11am

LK203/4 LK 205/6 LK208 LK209

Study section on Biochemical genetics

Cowan Niemi Cusmano Enns

No readings

11 Tues 11/2 9-11am LK130 Patient Panel (not videotaped)

TBA “Welcome to Holland”

12 Thurs 11/4 9-11am LK203/4 LK 205/6 LK208 LK209

Study section on genomics and complex disorders

Dudley Merker Morgan Sherlock

No readings

13 Tues 11/9 9-10am 10-11am

LK130 New Genetic Technologies Principles of stem cell and iPS cell biology

Snyder Baker

Snyder Du and Gerstein (2010). Genes Dev. 24(5):423-31. Pelak et al (2010) PLoS Genet 6(9): e1001111 Teo and Vallier (2010) Biochem. J. (2010) 428: 11–23.

14 Thurs 11/11 9-10am

LK203/4 LK 205/6 LK208 LK209

Journal Clubs on Genomics

Anderson Brown Karczewski Scharfe

Ng et al (2010) Nature Genet 42(1):30-5 Ng et al (2010) Nature Genet 42(9):790-94.

14

Thurs

11/11

10-11am

LK203/4

Optional Review Session on Genomics /New Technologies

Hudgins and Ormond

No readings

16 Tues 11/16 9-10am LK130 Gene and Cell

Therapy for Inherited Diseases

Calos Ch 12 (p 232-236); Fischer and Cavazzana-Calvo (2008) Lancet 371:2044

16 Tues 11/16 10-11am LK130 Pharmacoge-nomics

Carrillo Ch 12 (p 225-230); Roden et al. (2006) Ann Intern Med 145:749

17 Thurs 11/18 9-10am LK130 Genetics, Ethics and the Law

Greely Greely (1997) Oncology 11:171-6 Ormond et al (2010). Lancet 375(9727):1749-51.

18 Thurs 11/18 10-11am LK130 Optional review session on final 3 topics

No Classes

Week of

11/22- 11/26 Thanksgiving Week

Thurs 12/2 9-11am LK130 Review Session

TAs

Final Exam

Wed 12/9 8:30-11:30am.

LK130 (computers provided)

Computer based final examination

Course Objectives: The goals of this course are: 1) to learn how genetic reasoning is applied in principle and in practice to human health and disease through a combination of lectures and the cases presented in study sections, 2) to understand how recent advances in human genetics and genomics is currently, and will in the future, impact the diagnosis, prevention and treatment of human disease, and 3) to interact with patients and families who have experienced genetic disease in a professional manner. The following are a list of the major topics to be covered in this course. Knowledge of these areas will be required to pass the final exam. An undergraduate level knowledge of basic biochemistry and molecular biology principles (as well as background from the Molecular Mechanisms of Medicine course) will be extremely helpful.

Fundamentals of chromosome structure and function, including segregation and recombination

Fundamentals of gene structure and function, including genetic variation and mutation in human populations

Patterns of inheritance (Mendelian and non-Mendelian) Pedigree analysis and risk assessment Principles and practice of clinical genetic evaluation, testing, and counseling Genetic basis of various Mendelian and complex disorders seen in the prenatal, pediatric,

and adult settings Treatment of genetic diseases, including therapeutics, pharmacogenomics and gene

therapy Introduction to new genomic technologies and their clinical applications Social and ethical issues associated with genetic testing of individuals, families and

populations

Course Directors Kelly Ormond, MS, CGC (Genetics) [email protected] 6-9847 Louanne Hudgins, MD, FACMG, FAAP [email protected] 8-4937 (Pediatrics/ Medical Genetics, Obstetrics and Gynecology) Administrative associate to Professors Ormond and Hudgins: Heide 8-4937 Directions to the course directors’ offices in the basement of Boswell (A097) are posted on the coursework site. Professor Ormond’s office hours are typically Tuesdays from 1-3pm, Wednesdays from noon –

2pm, or by appointment. She will be unavailable 10/14-10/15, 11/1-11/5, 11/12 and Thanksgiving week, so please arrange alternative times in advance. You may contact either Professor Ormond or her administrative associate, Heide, to arrange appointments outside of office hours.

Dr. Hudgins’ office hours are to be arranged through her administrative associate, Heide. She

will also be unavailable 11/1-11/5.

Teaching Assistants Sarah Garcia, PhD (Human Genetics ’11) [email protected] Reana Tischler (Human Genetics ’11) [email protected] Kim Vande Wydeven (Human Genetics ’11) [email protected] Yuri Kim, PhD (MS II ’13) [email protected] Each of you will be assigned a TA for your study section. We encourage you to direct questions regarding course material to your assigned TA, or to the course directors. Additional Lecturers Julie Baker, PhD (Genetics) Michelle Calos, PhD (Genetics) Michelle Carrillo (PharmGKB) Greg Enns, MD (Pediatrics/ Medical Genetics) Jim Ford, MD (Medicine/Genetics) Hank Greeley, JD (Law, Genetics) Susan Schelley, MS, CGC (Pediatrics/Medical Genetics) Mike Snyder, PhD (Genetics) Study Section Instructors Matt Anderson, MD (Pathology) Jon Bernstein, MD, PhD (Pediatrics/Medical Genetics) Colleen Brown , MS, CGC (Cardiovascular Genetics) Tena Cherry, PhD (Pathology; Director, Cytogenetics Laboratory) Kelly Chen, MS, CGC (Prenatal Genetics) Nicki Chun, MS, CGC (Cancer Genetics) Tina Cowan, PhD (Pathology; Director, Biochemical Genetics Laboratory) Kristina Cusmano, MD (Metabolic Genetics) Joel Dudley, PhD (Bioinformatics) Greg Enns, MD (Pediatrics/Medical Genetics) Jim Ford, MD (Medicine, Genetics) Konrad Karczewski, PhD candidate (Genetics) Andrea Kwan, MS, CGC (Pediatrics/Medical Genetics) Uri Laudabaum, MD (Cancer Genetics) Alexandra Lebonsohn, MS, CGC (Cancer Genetics) Melanie Manning, MD (Pediatrics/Medical Genetics and Assoc Director, Cytogenetics Lab) Jason Merker, MD (Molecular and Cytogenetics Pathology Fellow) Alex Morgan, PhD candidate (Bioinformatics and Pediatrics) Eric Mueller, MD, PhD (Medical Genetics Fellow) Anna Kaisa Niemi, MD, PhD (Medical Genetics Fellow) Gavin Sherlock, PhD (Genetics) Joanne Taylor, MS, CGC (Prenatal Genetics) Doug Vollrath, MD, PhD (Genetics) Recommended Text --Students will find the following textbook a helpful reference during the course. It is available through the Stanford Bookstore and three copies are on reserve at Lane Library: Young I (2005) Medical Genetics. Oxford University Press, ISBN: 0-19-8564945

Additional readings will be posted on the Coursework website.

Grading There are 3 key components of this course that will contribute to your grade. First year medical students will receive a Pass/Fail grade for this course as follows:

Weekly problem sets (20%). There will be 5 problem sets on Coursework (see topics listed below). You are welcome to work with other students on the problem sets. In order to receive full credit for your weekly problem sets, you must complete all of the problem sets by their deadlines (the Wednesday 11:59pm, after the lecture and before the study section), and you must receive a grade of 70% or greater when we look overall at your total problem set score. If you do not complete all problem sets at this level, you will receive 0% for this component.

Attendance in study sections (5), the patient panel and the journal club session.

Participation in a group presentations at TWO study sections plus the genomics study session (20%). Attendance at all 5 study sections, the patient panel and the journal club is MANDATORY. If you are going to have to miss a study section, you must clear your absence IN ADVANCE with your TA (this includes planned medical issues!). In the event that you have an excused absence for a study section, you will have to turn in both of the study section cases within one week of the study section (to your TA) in order for your attendance to be counted. If you do not have 85% attendance (6 of 7 sessions) documented by December 1, 2010 you will receive 0% for this component.

Final examination. (60%). To pass the course, one must obtain a score of 70% or greater

or remedial work will be required to receive a passing grade. The final exam is scheduled for Wednesday, December 8, 2010, from 8:30-11:30am. We plan to administer the examination on computers using Coursework, and the exam will utilize USMLE type questions similar to those used on the weekly problem sets. Additional information will be available later in the semester.

For undergraduate or graduate students who opt to receive a letter grade, we will use your actual grades from the problem sets (rather than the “all or none” completion approach described above) and the final examination as follows: A= 90-100 B= 80-89 C= 70-79 D= 65-69 F = <65

Lectures: All lectures will be videotaped and available on the Coursework website, with the exception of patient speakers (11/2). Please make a note of this date so that you can be sure to attend class if you do not otherwise do so regularly. All slides will be posted prior to the lecture (typically the night before class) so that you can make notes on the online PDFs during or after class. We strongly encourage you to download them before class. Study Sections: The mandatory study sections will typically take place each Thursday for an hour, but there will be some variation in the specific times depending on if the other hour is a lecture or an optional review session with the course directors. Students are expected to attend all study sections, as these will not be taped, and will provide an interactive way to work through clinical cases. Attendance will be taken at all study sections; it is inappropriate to sign in for your classmates under any circumstances. The goal of the study sections is to work through the material and cases by discussion. Study sections will be facilitated by experts who practice in the area, including clinical geneticists, laboratory directors and genetic counselors, in combination with your course TAs. Discussion of cases will include interpretation of lab results and availability of resources for families and non geneticist physicians, including guidelines for clinical care. Each student will be assigned to present two study section case during the course of the semester. Groups of 5-6 students will be assigned to two cases across the first four case based study sections (Chromosome Disorders 10/7, Single Gene Disorders 10/14, Cancer Genetics 10/21 or Biochemical Genetics 10/28). All groups will be responsible for presenting a case at the Genomics and Complex Disorders Study Section on 11/4. In addition to presenting answers to all the questions for the case, you should also provide access to a recent review article (not included in the syllabus) that will assist in your classmates learning and mastery of the topic. You can email the paper in PDF form to your TA no later than the morning of the study section presentation.

Chromosomes 10/7 Single Gene 10/14 Cancer 10/21

Case 1 Case 2 Case 1 Case 2 Case 1 Case 2

Yuri Group A Group B Group C Group D Group A Group B

Sarah Group E Group F Group G Group H Group E Group F

Reana Group I Group J Group K Group L Group I Group J

Kim Group M Group N Group O Group P Group M Group N Biochemical 10/28 Genomics 11/4 Case 1 Case 2 Case 1/2 Case 3/4 Group C Group D A/B C/D Group G Group H E/F G/H Group K Group L I/J K/L Group O Group P M/N O/P

In addition to the Study Sections, students are also required to attend the patient panel (11/2) and journal club session (11/11). Attendance will be taken, and neither session will be videotaped. Problem Sets There will be five problem sets distributed as follows. Each will be due before the related study section, on the Wednesday (at 11:59pm) after the lecture occurs.

1) Prenatal Genetics and Common Chromosome Disorders (due 10/6/10, 11:59pm) 2) Single Gene Disorders and Risk Assessment (due 10/13/10, 11:59pm) 3) Cancer Genetics (due 10/20/10, 11:59pm) 4) Biochemical Genetics (due 10/27/10, 11:59pm) 5) Genomics (due 11/3/10, 11:59pm)

Course Evaluations An anonymous course evaluation will be online so that you can provide us with valuable feedback regarding the course organization, as well as regarding specific lectures. As you know, not only are evaluations a critical issue to the medical school for accreditation, but your thoughtful comments and constructive feedback will be helpful as we continue to revise this course in future years. We encourage you to jot down information regarding the course during the quarter so that you can provide us with thoughtful feedback about the entire course. As you also know, completion of your anonymous course evaluation will also allow the medical school to release your grades at an earlier opportunity. Course Policies: Students are expected to abide by the University’s Honor Code, which can be found at: http://www.stanford.edu/dept/vpsa/judicialaffairs/guiding/honorcode.htm Students are asked to turn cell phones or pagers to vibrate to minimize distractions during class. Students who choose to use computers for note-taking during class are asked to refrain from internet use in class. Students with documented disabilities: Students who have a disability that may necessitate an academic accommodation or the use of auxiliary aids and services in a class must initiate the request with the Disability Resource Center (DRC). The DRC will evaluate the request with required documentation, recommend appropriate accommodations, and prepare a verification letter dated in the current academic term in which the request is being made. Please contact the DRC as soon as possible; timely notice is needed to arrange for appropriate accommodations. The DRC is located at 563 Salvatierra Walk (723-1066; TDD 723-1067).

Genetics 202 Study Section Instructions Goals: To reinforce genetic concepts taught in class and apply them clinically. To better prepare you for the genetics component of your medical practice, including interpretation of lab results, availability of resources for families, and guidelines for clinical care. Format: The majority of each study section will be devoted to reviewing two clinical cases, which will serve to elucidate concepts presented in lecture. These cases are similar in format to cases that you will encounter on the final exam. A mastery of problem sets and clinical cases indicates a good understanding of the course material. Dates/Times: Study sections will typically take place for an hour each Thursday between 9-11am. Study Groups: Each small group will consist of 20-25 people and will be broken up into 4 smaller “study groups” of 5-6 students each. Group assignments will be posted to Coursework. Each study group is responsible for working together to prepare TWO assigned cases plus the assigned Genomics study section case. Cases: The cases are in your syllabus and also posted to Coursework in the “Study Section Materials” folder. EVERYONE should read each question carefully and answer all questions in advance of the study section, as this will enrich your learning experience. One study group will present each case. Presentations: Each group can present their case in whatever format they see fit. Many groups will opt for Powerpoint. You may find it useful to copy each question directly onto a Powerpoint slide and then insert your answers (along with relevant explanatory figures). Essentially, you are teaching your case to your classmates, with TAs and Genetics Experts to answer any additional questions or points of confusion. If your group is confused about a particular question or wants additional information, you can email your TA in advance of the class or ask for help during the class itself, but we strongly suggest that you not wait until the last minute to contact your TAs with questions. We expect the presentations to be an active learning experience for presenters and their classmates. Preparation for HHD: During Q3-Q5, medical students are expected to present cases for HHD that closely follow the format of Gene 202 cases. Therefore, this course will help to prepare you for HHD presentations. Attendance: Study section attendance is mandatory and will be taken at the start of each study section. It is inappropriate to sign in for anyone other than yourself. Absences must be excused by your TA in advance of the study section. To receive credit for the study section, you must complete BOTH cases for each study section you miss and submit those cases to your TA within one week of the study section. You must also help your group to prepare their presentation, if your absence coincides with your group’s presentation. Failure to meet these guidelines will result in a score of 0% for the study section portion of your grade.

Small group leaders: Each small group will have the same TA for duration of the course, who will serve as the facilitator for the study section. Your TA may be a medical student or a genetic counseling student. Additionally, each study group will be attended by at least one expert in the practice of medical genetics. These experts may be clinical geneticists, laboratory directors, or genetic counselors. Their goal is to assist you in understanding the lecture material and to guide you in its clinical application. Guidelines for Genetics Experts: Your role is primarily that of an expert consultant, rather than as a “presenter.” As much as possible, please allow the students to present their case without interruption, unless they ask specific questions, request feedback, or get very off track. The Teaching Assistants will be responsible for facilitating the session, and they may often defer to you for expert advice. Please review cases in advance of the study section.

Study Section group assignments Yuri Kim in Room LK 203/4 -- Groups A, B, C, D Sarah Garcia in Room LK 205/6 – Groups E, F, G, H Reana Tischler in Room LK208 – Groups I, J, K, L Kim VandeWydeven in Room LK 209 – Groups M, N, O, P

Human Genetics: GENE 202 Autumn 2010

Introduction to Medical Genetics; Course Overview Session type: Lecture September 28, 2010 -- 9-10am Louanne Hudgins, Kelly Ormond Goals

To understand the framework of GENE 202 including course requirements. To be familiar with electronic references for genetic conditions and genetic testing. To review the parts of a human gene and how they can be affected by mutation. To understand commonly used diagnostic methods to test the integrity of gene. To understand the reasons for using a pedigree to document family history information,

and to be familiar with the standardized symbols used to draw them. To begin to understand the importance of medical genetics in the practice of medicine

and to recognize the role of medical geneticists and genetic counselors in medical practice.

To appreciate the psychosocial impact of genetic disease and testing on an individual, including how it influences their requests for testing and the timing of such requests.

To appreciate the impact of genetic testing and test results on family dynamics.

Learning Objectives The student will be able to:

Accurately draw and interpret a pedigree o http://www.progenygenetics.com/online-pedigree/

Describe how mutations and genetic variation contribute to human disease List 3 benefits and limitations of genetic testing Compare direct mutation testing, linkage analysis, and association testing Describe the major components of a genetics evaluation and counseling session. List at least 3 possible reasons why a patient may consider or decline genetic counseling

and testing. List at least 3 ways in which genetic testing may impact the family. List resources in identifying genetics specialists Use GeneTest/GeneReviews and OMIM, as a line of reference for clinical genetic

diagnostics.

o http://genetests.org o http://www.ncbi.nlm.nih.gov/omim/ (you can google OMIM or enter via

PubMed)

Advance preparation: Read in Young: Ch 1, Ch 13 (p 243-244) Feero, Guttmacher Collins (2010) NEJM 362:2001-11. Uhlmann and Guttmacher (2008) JAMA. 299(11): 1356-8.

Assignment: None


Chromosomes and Prenatal Genetics Session type: Lecture September 28, 2010 – 10-11am and September 30, 9-11am Louanne Hudgins and Kelly Ormond Goals

To understand the difference between meiosis and mitosis and why meiosis is important for genetic variation.

To understand the differences between the features seen in individuals with abnormalities involving the autosomes versus the sex chromosomes.

To understand the difference between aneuploidy and structural chromosome abnormalities including recurrence risks.

To understand the genetic basis and clinical features of common chromosome disorders. To become familiar with the various laboratory techniques used in the cytogenetics lab

including karyotype, fluorescent in situ hybridization (FISH) and array comparative genomic hybridization (CGH).

To understand the difference between prenatal genetic screening and diagnosis and that the goal is to detect the greatest number of abnormalities while putting the fewest pregnancies at risk.

To understand the utility and limitations of prenatal ultrasound and maternal serum screening.

To understand the utility and limitations of preimplantation genetic diagnosis. To understand the concept of nondirective counseling and offering women and their

partners choices. To appreciate the psychosocial impact of genetic disease and testing on an individual,

including how it influences their requests for testing and the timing of such requests. To appreciate the impact of genetic testing and test results on family dynamics.


Describe the differences between meiosis and mitosis. Explain the difference between aneuploidy and structural chromosome abnormalities

including the underlying mechanisms and possible recurrence risks Identify under what circumstances the following cytogenetic tests would be indicated:

o Karyotype o Fluorescent in situ hybridization (FISH) o Array comparative genomic hybridization

Interpret cytogenetic results including: o Karyotype (including understanding parts of the chromosome and banding

nomenclature) o Fluorescent in situ hybridization (FISH) o Array comparative genomic hybridization

Describe the common features (including prognosis and recurrence risk) for trisomy 21, trisomy 18, trisomy 13, Turner syndrome, Klinefelter syndrome, XXX, XYY, and 22q11 deletion.

Demonstrate the use of databases and other web-based resources to determine the significance (or lack thereof) of specific microdeletions and duplications.

List at least 5 options available to couples who undertake prenatal genetic screening and diagnosis.

Recognize the patterns of maternal serum screening analytes seen in o Down syndrome o Trisomy 18 o Neural tube defects/abdominal wall defects

Describe the procedures, ideal timing, and associated risks available for obtaining fetal tissue for genetic diagnosis.

Explain the procedure of preimplantation genetic diagnosis (PGD) including the rationale and accuracy

List at least 3 possible reasons why a patient may consider or decline prenatal genetic counseling and testing.

List at least 3 ways in which prenatal genetic testing may impact the family. An additional resource to consult is: http://www.slh.wisc.edu/cytogenetics/abnormalities/nomenclature.dot

Advance preparation: Read in Young: Ch 2 and 3; Ch 14 (p 271-276);

Manning and Hudgins(2010) Genet Med epub

Assignments: Problem set: Prenatal Genetics and Common Chromosome Disorders (due 10/6/10, 11:59pm) Study Section: Review materials prior to session on 10/7. Groups A, B, E, F, I, J, M and N will be responsible for presenting the case material.


Single Gene Disorders Session type: Lecture October 5 (9-11am) and October 7 (9-10am) Kelly Ormond and Louanne Hudgins Goals

To understand Mendelian forms of inheritance (autosomal dominant and recessive, X linked dominant and recessive) and terms such as penetrance and expression.

To understand the concept of distribution of genes in a population and how it relates to genetic disease and population based screening.

To understand the use of the laws of addition and multiplication in calculating risk To appreciate the psychosocial impact of genetic disease and testing on an individual,



• Define and demonstrate use of examples of the following terms: penetrance, expression, anticipation, de novo, locus heterogeneity, allelic heterogeneity, genotype-phenotype correlations, mosaicism (germline and somatic).

• List the features of traditional modes of inheritance (autosomal dominant, recessive and X-linked).

• Calculate risks for various family members where there is a known mendelian or mitochondrial condition.

– Demonstrate when to use the law of addition and the law of multiplication • Calculate population carrier frequencies using Hardy Weinberg principle. • Define the following factors which influence Hardy-Weinberg distribution:

o Heterozygote advantage o Founder effect and genetic drift o Nonrandom mating o Migration and gene flow

• List reasons of how and why Bayesian Analysis is used to refine risk assessment. • List at least 3 possible reasons why a patient may consider or decline genetic counseling

and testing. • List at least 3 ways in which genetic testing may impact the family.

Advance preparation: Read in Young: Ch 4 (p 69-81) ; Ch 7 (p 135-138); Ch 13 (p 244-252) Assignments: Problem set: Single Gene Disorders and Risk Assessment (due 10/13/10, 11:59pm) Study Section: Review materials prior to session on 10/14. Groups C, D, G, H, K, L, O and P will be responsible for presenting the case material.


Chromosomes and Prenatal Genetics Session type: Small Group Discussions (Study Section) October 7 10-11am TAs and expert facilitators

Session Summary: Student groups will present the study section cases for discussion.

Advance preparation: Group assignments for presenting the study section cases are listed below.

Chromosomes 10/7 Case 1 Case 2 Group A Group B Group E Group F Group I Group J Group M Group N

Assignment: see attached. Presenting groups should prepare appropriate materials and students who are not presenting should review the cases in advance of the class session.

Chromosomes and Prenatal Genetics Study Section – Case 1 (10/7/10)

You are asked to evaluate a baby in the nursery who is turning dusky with feeds. Prenatal history is notable for a normal chromosome analysis via chorionic villus sampling (CVS) which was performed for advanced maternal age. Prenatal ultrasound at 18 weeks was reported to be normal. On physical exam, you note the following findings: a large anterior fontanelle, prominent forehead, deeply set eyes, and a harsh systolic murmur. You order an echocardiogram which reveals a large ventricular septal defect. You meet with the mother to obtain a family history and you construct a pedigree. She reports that she has had two miscarriages, both in the first trimester. She is an only child and both of her parents are in good health. She reports that her husband has a 30 year old sister who has not yet had children, and a maternal uncle who is developmentally disabled and whose appearance is different than other family members. His parents are in good health. 1. What tests would you like to order? 2. The test results are attached (see PDF attachments). What does this mean? 3. You are not familiar with this condition. Where would you look for information on this condition? 4. You meet with the parents to discuss this diagnosis and implications for their child. What do you tell the family? 5. What resources would you make available to the family? 6. The mother is quite distraught at this information and cannot understand why this wasn’t identified prenatally. What do you tell her? 7. The family is interested in having other children. In order to determine their recurrence risk, would you like to order any additional testing on the parents and, if so, what test would you like to order?

8. Results are attached. You meet with the parents again. What do you tell them regarding their recurrence risk? 9. Should any other family members be offered testing? 10. The father reports that he is estranged from his sister. How would you proceed?

Chromosomes and Prenatal Genetics Study Section – Case 2 (10/7/10) Emily is a six year old girl who presents for her annual school physical. She has had no major health problems and her developmental history is normal. Prenatal history was reported to be unremarkable. Her birth weight was 7 lbs. and her birth length was 20 inches. On physical exam, you note that her height is below the 3rd centile. She appears proportionate and her arm span is equal to her height. She has no significant minor anomalies. You obtain a family history and construct a pedigree. You note that her mother is 5’8” and her father is 6’. 1. What tests would you offer? The results of the test you order are attached.

2. You are surprised by the results. Where do you look to learn more about this condition?

3. What is the clinical diagnosis associated with this condition, and how do the patients features match the “typical” features? 4. You meet with the family to discuss this diagnosis. They are shocked and state that this isn’t possible since they have no family history of any chromosome abnormalities. How do you respond keeping in mind the mechanism for this chromosome difference? 5. Would you recommend sending parental chromosome analyses? 6. What is their recurrence risk for having other children with this condition? 7. Would you like to order any evaluations on Emily? 8. Her studies are normal. Are there other issues you should discuss with the family regarding Emily’s future health? 9. The parents ask whether Emily can be a mother. How do you respond?


Cancer Genetics Session type: Lecture October 12, 2010 – 9-11am Jim Ford Goals

To understand the role of oncogenes, tumor suppressors and DNA repair genes in the development of cancer.

To understand the difference between sporadic, familial and inherited cancer syndromes To recognize the “red flags” that suggest familial cancer susceptibility. To be aware of the medical and psychological risks and benefits to cancer susceptibility

genetic testing. To appreciate the psychosocial impact of genetic disease and testing on an individual,



Define oncogene and tumor suppressor. Differentiate between sporadic, familial and inherited cancer syndromes. List at least 3 “common” inherited cancer syndromes. List at least 3 factors that suggest familial cancer susceptibility. Describe the most effective process for genetic testing in a family where an inherited

cancer syndrome is suspected. List the essential features of informed consent for cancer predisposition testing. List 3 medical benefits for patients found to carry a cancer susceptibility mutation. List at least 3 possible reasons why a patient may consider or decline cancer genetic

counseling and testing. List at least 3 ways in which cancer genetic testing may impact the family.

Advance preparation: Read: Young Ch 10; Pollack and Welsh (2010) Am J Clin Oncol epub; Shulman (2010) Obstet Gynecol Clin North Am. 37(1):109-33

Assignments: 1) Problem set: Cancer Genetics (due 10/20/10, 11:59pm)

Study Section: Review materials prior to session on 10/21. Groups A, B, E, F, I, J, M and N will be responsible for presenting the case material.


Nonmendelian Inheritance Session type: Lecture October 14 9-10am Louanne Hudgins Goals

To become familiar with non-traditional forms of inheritance such as imprinting, mitochondrial inheritance, and multifactorial/polygenic inheritance.


• Describe how and why imprinting occurs, and list several examples of conditions where imprinting plays a role.

• List the features that differentiate mitochondrially inherited conditions from mendelian conditions.

• Calculate risks for various family members where there is a known condition that follows mitochondrial or non-mendelian inheritance

Advance preparation: Read in Young: Ch 4 pp 81-88

Optional: Siegel and Slavotinek (2005) Ped Derm 22:482-7.

Assignment: None


Single Gene Disorders Session type: Small Group Discussions (Study Section) October 14 10-11am TAs and expert facilitators

Session Summary:

Advance preparation: Group assignments are below for presentation of the study section cases.

Single Gene 10/14 Case 1 Case 2 Group C Group D Group G Group H Group K Group L Group O Group P


Single Gene Disorders -- Case Study 1

Max is a six month old male who failed his newborn hearing screen. Profound sensorineural hearing loss (SNHL) was confirmed by auditory brainstem response (ABR). Medical history is negative for any other health-related issues. Family history: Max has a five year old brother, Tony, who is in excellent health. Mom reports that she is in the third month of her third pregnancy. Max’ father, Jim, has two sisters and his mother, Anne, has two brothers. Jim's and Anne's parents have died. There is no history of illness in the family. Both Max's father and mother are of Greek descent. Consanguinity is denied. On physical exam, you note that Max is a nondysmorphic, that is, he does not have any minor anomalies to suggest a genetic syndrome. 1. Draw the pedigree.

2. What is the most likely mode of inheritance?

3. Mutations in what gene are responsible for ~50% of this form of hearing loss?

4. You perform testing for this gene and identify a homozygous mutation. What is the probability that the unborn fetus will have hereditary hearing impairment? What is the chance that the fetus is a carrier?

5. Tony has normal hearing, what is the probability that he is a carrier?

6. Assume the DNA testing reveals that Max is homozygous for the 35delG mutation, what type of prenatal analysis is possible for the fetus? What are the advantages and disadvantages of this testing?

7. What if the testing on Max showed that he had only one copy of the 35delG mutation on the specific allele testing? Are there additional tests you would order?

8. You exhaust all the current testing options and you are unsuccessful at identifying a second mutation in Max. How do you interpret this information? What does this mean for the fetus and testing during pregnancy?

9. One of Jim's sisters, Alice, has normal hearing and is found to have the 35delG mutation. Assume the incidence of hearing loss due to a GJB2 mutation in the Caucasian population is 1/2500. What is the chance that Alice and her husband will have a child with congenital hearing impairment? 10. Assume Max is homozygous for the 35delG mutation, and Jim does not have a 35delG allele. How would you proceed with counseling the couple?

Single Gene Disorders - Case Study 2 (10/14/10)

Hank is a 42 year old male who comes to your office complaining of excessive fatigue. His physical exam is normal, but laboratory testing reveals an elevated serum creatinine level of 5.7 mg/dl. (Serum creatinine is a measure of renal function. The upper limits of normal for this test for a male of average habitus is 1.2 mg/dl). You obtain a renal ultrasound examination, which reveals abnormally large kidneys with multiple cysts bilaterally. Upon further questioning you discover that his father, Harry, died of renal failure. You obtain medical records, and find that Harry had numerous cysts in both kidneys. Harry has six siblings, all of whom are alive and well. Hank has four siblings, Peter, Jacqueline, John, and Lawrence (ages 22, 39, 47, and 50 respectively). Hank's paternal grandmother and grandfather are both alive and well at the age of 93 and 96 respectively. Hank and his wife, Eleanor, have three children: Ron (22 years old), Natalie (18 years old), and Barbara (16 years old). 1. You make a provisional diagnosis of polycystic kidney disease (PKD), an autosomal dominant condition. Draw the family's pedigree. 2. What is the risk to Hank's children of having inherited the gene for PKD? 3. Ultrasound examination of Hank's older brother, John, reveals the presence of bilateral cysts in the kidneys, and you assign him a diagnosis of PKD. His creatinine level is only 1.8, and Hank is confused about why his bother's renal disease seems to be more mild than his own. How do you explain this to Hank? 4. The penetrance of PKD is 100% by age 90. You obtain medical records from Hank's paternal grandparents, and find that they both recently have had normal results on renal ultrasound and creatinine testing.

a. What implications does this information have for determining where in the pedigree the causative mutation arose?

b. Given this information, what is the risk to Harry's siblings of developing PKD? 5. Hank suddenly hears from his long-lost paternal uncle, Richard (Harry's brother). Richard is in renal failure and has multiple bilateral renal cysts.

a. How might you reconcile this information with you answer to question 3,

immediately above? b. How does this new information change your risk assessment for Harry's other siblings?

6. Lawrence seeks counseling regarding whether he has inherited the PKD gene. His renal ultrasound examination is normal. A recent study of individuals with PKD provides data suggesting that by the age of 50, 90% of individuals who carry the PKD gene will have an abnormal renal ultrasound exam. How would you counsel Lawrence? 7. You learn that 95% of cases of PKD result from mutations in a gene PKD1 located on chromosome 16. How do you explain the fact that 5% of cases do not appear to be the result of mutations in this gene? 8. Natalie desires testing. Because the mutation in the PKD gene has not been identified for this family, direct DNA testing is not possible. A linkage analysis is performed to determine who has inherited the PKD gene using a highly informative multi-allelic marker near the chromosome 16 PKD gene. You are able to analyze Harry's DNA from material that had been saved from autopsy. Harry's genotype at this marker locus is 1,2. Hank's genotype is 3,2. Eleanor's genotype is 4,7, and Natalie's genotype is 4,2. Is Natalie likely to have inherited the PKD gene from her father?


Biochemical Genetics Session type: Lecture October 19 9-11am Greg Enns and Susan Schelley Goals

To understand that inborn errors of metabolism occur due to an enzyme deficiency, which leads to a shortage of substrate and/or buildup of toxic metabolites.

To recognize signs and symptoms associated with inborn errors of metabolism. To be able to identify clues to an underlying inborn error of metabolism by using simple

lab tests. To understand the rationale underlying acute and chronic therapy for metabolic disorders,

including stem cell and solid organ transplantation. To understand the basics of expanded newborn screening including rationale. To recognize the importance of the team approach in effective treatment of children and

adults with inborn errors of metabolism. To appreciate the psychosocial impact of biochemical genetic disease. To appreciate the impact of genetic testing and test results on family dynamics.


Describe the typical signs and symptoms suggestive of an inborn error of metabolism. Describe the findings on routine laboratory tests, e.g. hypoglycemia, which are

suggestive of an inborn error of metabolism. Explain the difference in acute and chronic therapy for metabolic disorders such as urea

cycle disorders. Describe the potential benefits and pitfalls of different methods used for treating

lysosomal disorders. Name three conditions for which hematopoetic stem cell or solid organ transplantation is

used in treating inborn errors of metabolism and explain how the transplant works to treat the condition.

Describe the major categories of disorders for which expanded newborn screening is utilized and what techniques are used for each of the categories.

List at least 3 ways in which the diagnosis of a biochemical genetic disorder may impact the family.

Advance preparation: Read in Young: Ch 11; Levy (2009) Pediatr Rev 30;131

Assignments: Problem set: Biochemical Genetics (due 10/27/10, 11:59pm) Study Section: Review materials prior to session on 10/28. Groups C, D, G, H, K, L, O and P will be responsible for presenting the case material.


Cancer Genetics Session type: Small Group Discussions (Study Section) October 21 (9-10am) TAs and expert facilitators

Session Summary:


Cancer 10/21

Case 1 Case 2 Group A Group B Group E Group F Group I Group J Group M Group N


Cancer Genetics Study Section – Case 1 (10/21/10)

You meet Jane Jones, a 36-year-old woman, in your high risk cancer clinic, who seeks your opinion regarding her risk of developing cancer. The genetic counselor makes the appropriate phone calls, reviews the medical records, and completes the pedigree. Professor Jones reports the following family history: Professor Jones is 36 years old, with two daughters ages 14 and 11. Professor Jones has one sister, age 34, with a son, age 8. Professor Jones has one brother age 40, with one daughter age 19. Professor Jones’ father is 60, has no personal history of cancer, and is adopted. Professor Jones’ mother was diagnosed with breast cancer at age 46, which was treated with a modified radical mastectomy and chemotherapy, but passed away at age 50 from her battle with breast cancer. Professor Jones’ maternal aunt was diagnosed with breast cancer at age 47 and was recently diagnosed with ovarian cancer at the age of 51; she has two sons. Professor Jones’ maternal grandfather is deceased in his 70’s from “old age”. Professor Jones’ maternal grandfather had a brother with prostate cancer at age 40; that great-uncle has a daughter with breast cancer in her 30’s. Professor Jones’ maternal grandmother died in her 80’s of “natural causes.” Maternal ancestry is English and Irish. Paternal ancestry is unknown. There is no consanguinity. Professor Jones wishes to have genetic testing because she’s heard that there are some “breast cancer genes” and she is worried about her own risk for cancer and also for her daughters.

1. Draw the pedigree.

2. Is the cancer being inherited in this family? If so, what appears to be the mode of inheritance in this family?

3. What hereditary cancer syndrome would you consider as the most likely explanation in the family? What specific characteristics of her family history guided your consideration?

4. What testing would you offer to this family?

5. Who would be the most appropriate person to offer genetic testing to, and why?

6. If that person comes back with a negative test result, how will we interpret that result and what will we do next?

7. If that person comes back positive, how will we interpret that result and what will we do next?

8. If Professor Jones is found to have a true negative result, what is the risk of breast cancer for her daughters?

9. If Professor Jones is found to have a positive result, what are the breast cancer risks for

her daughters?

10. If Professor Jones is found to have a mutation in the specific gene you tested for, what medical management can you offer her and what recommendations will you make?

11. If a mutation in this family is identified, who else in the family is eligible to undergo testing? What kind of testing would you order for them?

Cancer Genetics Study Section – Case 2 (10/21/10) You are asked to consult on Jeff Bates, a 46-year-old man who has been diagnosed with colon cancer. Through taking a cancer-focused family history, you discover that Mr. Bates’ sister was diagnosed with uterine cancer at age 47. Mr. Bates’ brother had a screening colonoscopy when his brother was diagnosed with colon cancer and no polyps were found. Mr. Bates’ mother was diagnosed with uterine cancer at 50 years old, and Mr. Bates’ maternal uncle passed away from colon cancer at 65 years old. You should draw out the pedigree for this family to help you in answering the following questions.

1. Does this family appear to have sporadic, familial, or hereditary cancer? If hereditary, what appears to be the mode of inheritance in this family?

2. What hereditary cancer syndrome would you consider as the most likely explanation for

the cancer in this family? What specific characteristics of this family guided your consideration?

3. Since you are a very astute clinician with a strong working knowledge of hereditary

cancer, you request the pathology reports from Mr. Bates’ biopsies to assist you in your evaluation. The pathology report reveals a right-sided adenocarcinoma with mucinous signet ring-cell features. Does this increase or decrease your suspicion for a hereditary cancer syndrome? Why?

4. Explain microsatellite instability. Would you order microsatellite instability (MSI) tumor

studies on Mr. Bates’ tumor? If so, why?

5. You are at an institution that allows you to pursue other studies before going directly to molecular genetic testing. You order microsatellite instability (MSI) and immunohistochemical protein staining on Mr. Bates’ tumor. What are the benefits to doing tumor studies before molecular testing?

6. Tumor studies reveal that Mr. Bates’ tumor is MSI-high with 5/7 markers shifted and

there is loss of staining by immunohistochemistry of MLH1 and PMS2. What does this mean? What is your next step?

7. Who in the family is at risk of having this hereditary cancer syndrome?

8. What are the cancer risks associated with this hereditary cancer syndrome?

9. What are the medical management and surveillance recommendations for Mr. Bates?

What options would you offer other family members who carry the familial mutation?


Optional review session Session type: Small Group Discussions October 21 10-11am Louanne Hudgins and Kelly Ormond


Genomics and Complex Disorders Session type: Lecture October 26 (9-11am) and October 28 (9-10am) Louanne Hudgins and Kelly Ormond Goals

To become aware of the current status of genetic studies (e.g. genome wide association studies, GWAS) for complex multifactorial genetic conditions, including the limitations and future potential of such study approaches.

To become familiar with current genetic research for common diseases using the example of diabetes

To understand how rare genetic conditions can provide insight into the pathophysiology of common disorders.

To think about ways that this current research may impact current and future clinical practice.

To appreciate the psychosocial impact of genetic disease and testing on an individual, including how it influences their requests for testing and the timing of such requests.

To appreciate the impact of genetic testing and test results on family dynamics. Learning Objectives The student will be able to:

Describe how polymorphisms are used as genetic markers. Describe how genetic information can provide insight into underlying pathways. Describe how a GWAS study is conducted. List at least 2 current benefits and limitations of this genetic data. Differentiate between predictive genetic testing and susceptibility genetic testing. List at least 3 possible reasons why a patient may consider or decline genomic counseling

and testing. List at least 3 ways in which genomic testing may impact the individual and/or family.

Advance preparation: Read: Young Ch 6

Manolio 2010. N Engl J Med; 363:166-176 Manolio et al. 2009; Nature. 461(7265):747-53. Pearson and Manolio (2008) JAMA 299:1335.

Assignments:

1) Problem set: Genomics (due 11/3/10, 11:59pm) 2) Study Section: Review materials prior to session on 11/4. All groups will be responsible

for presenting the case material.


Biochemical Genetics Session type: Small Group Discussions (Study Section) October 28 (10-11am) TAs and expert facilitators

Session Summary:


Biochemical Genetics Case 1 Case 2 Group C Group D Group G Group H Group K Group L Group O Group P


Biochemical Genetics Study Section – Case 1 (11/28/10) You are asked to evaluate a three day old male infant in your office for a routine newborn examination after hospital discharge. He is the first child born at full term to a 35 year old G1 P1 mother and 33 year old father following an uncomplicated pregnancy. He was delivered vaginally without complication with Apgar scores of 9 and 9. He did not require any special care after delivery and was discharged at 36 hours of age breastfeeding well. The parents now report that for the past 12 hours or so, their son has been lethargic and feeding poorly. They also report that he is “breathing rapidly”. Family history is unremarkable with no known neonatal deaths, congenital anomalies or mental retardation. On physical examination you note that the infant has an increased respiratory rate, low muscle tone, and does not respond well to stimuli. 1. What is your differential diagnosis for this patient (suspend for a moment your knowledge that this is a metabolism discussion section)? 2. What screening tests would you like to order? 3. The pH is high and PCO2 is very low (normal bicarbonate). Why? 4. What does this pattern in the blood gas suggest? 5. Based on this blood gas pattern, an additional test is urgently indicated. What is it? 6. The analyte ordered above is found to be highly elevated. What is the most likely diagnostic category? 7. What is the relationship between this laboratory finding and the patient’s clinical status? 8. What type of care should this infant receive? 9. Do you have enough information to know where the metabolic block lies in the pathway below?

10. What additional testing would you like to order? 11. Testing reveals decreased plasma citrulline and elevated orotic acid. Based on these results, now do you know where the metabolic block is? 12. Would your answer be different if this was a female patient? 13. What is the prognosis for this patient? 14. What is the pattern of inheritance of this disorder? 15. How will you do carrier testing? 16. What is the recurrence risk? 17. What options are available for future pregnancies?

18. How is this disorder managed? 19. What resources are available to support the patient and family?

Biochemical Genetics Study Section – Case 2 (11/28/10) You are asked to evaluate Russell, a 3‐day‐old male infant referred for an abnormal newborn screening result. Russell was born at full term to a 35-year old G3 P3 mother and 33-year old father following an uncomplicated pregnancy. He was delivered vaginally without complication with Apgar scores of 9 and 9. He did not require any special care after delivery and was discharged at 36 hours of age breastfeeding well. The parents have no concerns about Russell’s health, and report that he is a quiet baby who sleeps much of the time. Russell has a healthy 4-year old sister, as well as a brother who died in infancy of unknown causes. Family history reveals that the maternal and paternal grandfathers are brothers. There are no other known neonatal deaths, congenital anomalies or mental retardation in the family. On physical examination, however, you find him to be markedly hypotonic with deep, labored breathing (Kussmaul respirations). Russell is immediately admitted to the hospital for further evaluation, where laboratory studies reveal pH 7.1 (normal 7.35-7.45), CO2 20 mmHg (normal 35-45), bicarbonate 8mEq/L (normal 22-26), anion gap of 32 (normal <15), ammonia 500uM (normal <30), glucose 20mg/dl (normal 60-100), and lactate 8mM (normal <2.5).

1) Draw the pedigree for this family.

2) What general categories of inborn errors of metabolism are identified by expanded newborn screening?

3) Based on Russell’s laboratory findings, in which of the disease categories do you suspect a problem?

4) Upon further investigation, you discover that Russell’s newborn screen was abnormal for an elevation of propionylcarnitine (C3‐carnitine), concerning for methylmalonic acidemia or propionic acidemia. What tests would you order to distinguish between the two?

5) Based on the result shown below, what is your diagnosis for Russell?

6) There is treatment available for Russell. Briefly describe the options for his immediate care as well as for the long‐term management of his condition.

7) The family would like written information about this condition to share with their families. What resources would you give them?

8) How would you counsel the parents about further pregnancies?

9) Should anyone else in Russell’s family be tested for the same condition? Why or why not?

TIC: 11270706.

3-OH propionate

Methylmalonic acid

Propionylglycine Methylcitric acid


Patient Panel Session type: Lecture (not videotaped) November 2 Patients TBA Advance preparation: Read “Welcome to Holland” Students should dress appropriately for this patient session. There will be the opportunity to ask questions of the presenters. This session is required, and students will sign in to document their attendance.


Genomics and Complex Disorders Session type: Small Group Discussions (Study Section) November 4 (9-11am) TAs and expert facilitators

Session Summary:


Genomics 11/4 Case 1/2 Case 2 A/B Group C/D E/F Group G/H I/J Group K/ L M/N Group O/P


Genomics study sections will be inserted later in the quarter


New Genetic Technologies Session type: Lecture November 9 (9-10am) Mike Snyder

Goals To understand the current state of sequencing technologies and their application to

clinical medicine. To understand the advantages and challenges of next-gen sequencing.


Describe how next generation sequencing technology is performed Compare the information obtained from exome sequencing versus whole genome

sequencing List at least 3 types of clinical information that can be obtained from the various

sequencing technologies .

Advance preparation: Read: Snyder Du and Gerstein (2010). Genes Dev. 24(5):423-31. Pelak et al (2010) PLoS Genet 6(9): e1001111

Assignment: Review articles for journal club using this material as background.


Principles of Stem Cells and iPS cells Session type: Lecture November 9 (10-11am) Julie Baker

Goals

To understand the biologic premises that underlie stem cell and iPS cell development. To understand how embryonic and adult stem cell lines are created. To describe the process of nuclear transfer. To understand the advantages and disadvantages of various regenerative medicine

approaches. Learning Objectives The student will be able to:

Define totipotent, pluripotent and multipotent List at least 3 locations from which adult stem cells can be derived List at least 2 problems or challenges that have arisen in the use of adult stem cells List at least 2 ethical challenges to the use of embryonic stem cells List at least 2 ways that iPS cells differ from traditional stem cell lines.

Advance preparation: Read: Teo and Vallier (2010) Biochem. J. (2010) 428: 11–23.

Assignment: None


Genomics Journal Club Session type: Small Group Discussions (Study Section) November 11 (9-10am) TAs and expert facilitators

Advance preparation: Read Ng et al (2010) Nature Genet 42(1):30-5. Ng et al (2010) Nature Genet 42(9):790-94.

Be prepared to discuss the articles and any questions you have about methodology or findings


Optional review session on Genomics and New Technologies Session type: Small Group Discussions (Study Section) November 11 (10-11am) Louanne Hudgins and Kelly Ormond


Gene and Cell Based Therapy for Inherited Disorders Session type: Lecture November 16 (9-10am) Michele Calos Goals

To understand the challenges of gene therapy, which include getting the functioning gene into the correct cell type and achieving life-long expression.

To understand the advantages and disadvantages of various vectors for gene therapy. Learning Objectives The student will be able to:

Define gene therapy List 2 potential goals of treatment through gene therapy List at least 3 disorders where gene or cell based therapies have been investigated, and

why the therapy was or was not successful List 3 general challenges or potential risks to effective gene therapy.

Advance preparation: Read in Young: Ch 12 (p 232-236);

Fischer and Cavazzana-Calvo Lancet 371:2044

Assignment: None

Human Genetics: GENE 202

Autumn 2010 Pharmacogenomics Session type: Lecture November 16 (10-11am) Michele Carrillo Goals

To understand how genes play a role in pharmacodynamics (PD) and pharmacokinetics (PK).

To understand the challenges in introducing genetics into routine drug prescribing. To be able to explain one case of how genetics can improve drug efficacy or reduce side

effects. Learning Objectives The student will be able to:

Define pharmacogenomics. List 3 potential benefits of using pharmacogenetic information. List at least 3 barriers to broad use of pharmacogenetic information. List at least 3 current examples of where pharmacogenetic data may impact drug dosing. Discuss the difference between race-based prescribing versus pharmacogenetic

prescribing. Advance preparation: Read in Young: Ch 12 (p 225-230);

Roden et al. (2006) Ann Intern Med 145:749 Optional: Explore PharmGKB.org website

Assignment: None


Genetics, Ethics and the Law Session type: Lecture November 19 (9-10am) Hank Greely

Goals To understand the key ethical issues as they relate to genetic testing and counseling. To appreciate the complexity of ethical issues associated with genetic testing through

case examples. Learning objectives: The student will be able to:

List at least 3 possible reasons why a patient may consider or decline genetic counseling and testing.

Apply ethical concepts including confidentiality, autonomy, and justice to genetic testing situations.

Advance preparation: Read: Greely (1997) Oncology 11:171-6 Ormond et al (2010). Lancet 375(9727):1749-51.

Assignment: None


Optional review session (Cell based therapies, pharmacogenomics, ethics/law) Session type: Small group discussion November 19 (10-11am) Louanne Hudgins and Kelly Ormond

genetics 202 human genetics -...

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