# Medical Genomics 2025 Lecture Notes

## Lecture 1. History of Medical Genetics
Jan 14, 2025

[Lecture slides](https://docs.google.com/presentation/d/1pU058kD-cy0HRGhbZ6Hd6S3t76McvVGcwka9YxE8cVk/edit#slide=id.p
) on Google slides
[The life of Gregor Mendel video](https://youtu.be/95SL6UbP3ww) on YouTube
[Analyzing Mendel's DNA](https://www.npr.org/sections/health-shots/2022/12/30/1142202365/gregor-mendel-genetics-dna-analyzed) on NPR
[Talking glossary of genomic and genetics terms](https://www.genome.gov/genetics-glossary) (NHGRI)
[Student survey](https://docs.google.com/document/d/1UkLfcGieXFFOZBNtjBeUiR_8q2GbTDjyPzgpgYOU1-c/edit)

## Lecture 2. Molecular basis of heredity

January 16, 2025
[Lecture slides](https://docs.google.com/presentation/d/1afzV6lNE51YG2nh2NLVmFimWG_T82bNG-Pl7c0t1wSE/edit?usp=sharing) on Google slides
[What is DNA?](https://www.genome.gov/genetics-glossary/Deoxyribonucleic-Acid
) A definition from the NHGRI
*[DNA structure](https://www.youtube.com/watch?v=o_-6JXLYS-k
) MIT Bio **movie**
[What is a chromosome?](https://www.genome.gov/genetics-glossary/Chromosome) A definition from the NHGRI
*[The scale of the human genome](https://www.youtube.com/watch?v=eLmElwzOCdU) A **video** from NHGRI
[What is a karyotype?](https://www.genome.gov/genetics-glossary/Karyotype) A definition from the NHGRI
[What is replication?](https://www.genome.gov/genetics-glossary/DNA-Replication) A definition from the NHGRI
[What is RNA?](https://www.genome.gov/genetics-glossary/RNA-Ribonucleic-Acid
) A definition from the NHGRI
*[Translation:](https://www.youtube.com/watch?v=oCp9IK6iBTo) A **video** from the NHGRI
[Genetic code](https://educationalgames.nobelprize.org/educational/medicine/dna/a/translation/gencode.html)
[Problem set 1](https://docs.google.com/document/d/153tOfmxTMRrqQVd1jnFZMXUmjUcR9GByFJKENTVrVIw/edit)
[Answers](https://docs.google.com/document/d/1l1S5WBzbjf3XckgSwUSQzgyk_1dPLZM9NEILCLXcrGg/edit?usp=sharing) to Problem set 1

## Lecture 3. Human Genome Project

January 21, 2025

[Lecture slides](https://docs.google.com/presentation/d/1nUpto8YGgmHMrAinkzeUXLG_XjhvC3LUK8tCf8SQlcE/edit?usp=sharing) on Google slides
Illumina sequencing : An introductory [video](https://www.youtube.com/watch?v=fCd6B5HRaZ8)
The Genome War [book](https://www.amazon.com/Genome-War-Craig-Venter-Capture/dp/0345433742)
An [article](https://www.statnews.com/2024/07/09/human-genome-project-untold-story-how-single-volunteer-became-genetics-foundation/) about the donors for the public effort of the Human Genome Project
A [video](https://m.youtube.com/watch?v=UDqW_0bKAH8) about how to sequence a human genome in 7 easy steps
[Lessons from the Human Genome Project:](https://www.youtube.com/watch?v=qOW5e4BgEa4) A video from the NHGRI
[Telomere-to-telomere(T2T) Human Genome](https://www.youtube.com/watch?v=Jm-q47oPSm4&t=111s): A video by UC Santa Cruz featuring Karen Miga
PacBio Sequencing: An introductory [video](https://www.youtube.com/watch?v=NHCJ8PtYCFc)
Oxford Nanopore Technologies: An introductory [video](https://www.youtube.com/watch?v=GUb1TZvMWsw)
Y chromosome sequenced: [The Y interview at Science Friday, NPR](https://www.sciencefriday.com/segments/y-chromosome-fully-sequenced/)- 17 min
Y chromosome [paper](https://www.nature.com/articles/s41586-023-06457-y) in Nature 2023
A Sci American [article](https://www.scientificamerican.com/article/the-complete-human-y-chromosome-marks-an-opportunity-to-move-away-from-stigma/) about the Y chromosome
43 human Y chromosomes sequenced and assembled - a [paper](https://www.nature.com/articles/s41586-023-06425-6) in Nature 2023

## Lecture 4. Human Genome and Its Variation

January 23, 2025

[Lecture slides](https://docs.google.com/presentation/d/1Nby1Hpk81TVMiyhE1nHOUanUzUgzzT0y1r8QjG_Q8Xs/edit?usp=sharing) on Google slides
[A paper](https://www.nature.com/articles/35057050) summarizing the functions of disease genes depending on the typical age of onset
[The website of the 1000 Genomes Project](https://www.internationalgenome.org/home)
[A paper](https://www.nature.com/articles/nature15393) describing the results of the 1000 Genomes project, published in Nature
[A paper](https://www.sciencedirect.com/science/article/pii/S0092867422009916?via%3Dihub) describing results of the 1000 Genomes project Phase 4, published in Cell
An article by Oni-Orisan et al. '[Embracing Genetic Diversity to Improve Black Health](https://www.nejm.org/doi/10.1056/NEJMms2031080?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed)'
[The website of the Human Pangenome Project](https://humanpangenome.org/)
A Nature [publication](https://www.nature.com/articles/s41586-022-04601-8) describing the Human Pangenome Project
Human Pangenome Project: an introductory [video](https://www.youtube.com/watch?v=swNtGe9QWAQ) from minute 2:40

## Lecture 5. Chromosomes and chromosome abnormalities

January 28, 2025

[Lecture slides](https://docs.google.com/presentation/d/1gli-8Kjo1KGPFhLJzQKk-ZNxhJsZvoTPisXjYvmS20A/edit?usp=sharing) on Google slides
Nobel prize on telomeres and telomerase: an NPR [audio](https://www.npr.org/2009/10/05/113491995/americans-win-nobel-for-research-on-aging)
A [paper](https://www.science.org/doi/10.1126/science.abl4178) describing the complete sequences of human centromeres
The UCSC Genome Browser [website](https://genome.ucsc.edu/cgi-bin/hgGateway)
[Educational resources](https://genome.ucsc.edu/training/education/) at the UCSC Genome Browser

## Lecture 6. Mutations and paternal age effect

January 30, 2025

[Lecture slides](https://docs.google.com/presentation/d/18B06uq3nptgTPx1j1PvduvrMr2_w9Gf2FVGeGlFiRbQ/edit?usp=sharing) on Google slides
[Problem set 2](https://docs.google.com/document/d/1HEcdGO3ptd9s654sbRXnzrIa2rY7wLWPKg_0HYlvJpU/edit?usp=sharing
)
Problem set 2 [solutions](https://docs.google.com/document/d/1LqrM2FfdrbPiCa7-xAEWR6dTff9JNhPaqRqQ_Er1HDg/edit?usp=sharing)

## Lecture 7. Presentations on mutations

February 4, 2025

[Rubric](https://docs.google.com/document/d/16Zlcb_EHkCpRscRaV4zAFkJn5heESkHzHsPe1YfCOEg/edit?usp=sharing)
[Kong et al. 2012](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3548427/) - Group 1
[Sasani et al. 2019](https://elifesciences.org/articles/46922) - Group 2
[Gruhn et al. 2019](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212007/), this [paper](https://www.nature.com/articles/s41576-022-00573-7) might also help - Group 3
[Wyrobek et al. 2006](https://www.pnas.org/doi/abs/10.1073/pnas.0506468103?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed) - Group 4

## Lecture 8. Monogenic disorders

February 6, 2025

[Lecture slides](https://docs.google.com/presentation/d/14O15yV9pOXMQukwPM0ewB1KTlqA5wcgUsyem6aBF3yw/edit?usp=sharing) on Google slides
An [article](https://pubmed.ncbi.nlm.nih.gov/9254745/) about porphyria variegata
An [article](https://www.aimspress.com/article/doi/10.3934/molsci.2021005?viewType=HTML) about alkaptonuria
An [article](https://www.researchgate.net/figure/Pedigree-of-the-AZFc-deleted-family-Black-boxes-indicate-that-an-AZFc-microdeletion-was_fig2_5367584) about transmitted azoospermia
[Problem set 3](https://docs.google.com/document/d/1b2_Q7vyRFXDj_REUtYKtWqNhQPtqREy2XEnrOM-hbvQ/edit?usp=sharing)
Problem set 3 [solutions](https://docs.google.com/document/d/1LIX0RBOzzKspttR53qyNRtbdZLsAbrW28Hhw23Oa-RM/edit?usp=sharing)

## Lecture 9. Mitochondrial mutations and diseases

February 11, 2025

Lecture [video](https://live.libraries.psu.edu/Mediasite/Play/a842a2ef6e6644aca8af918188154a1c1d)
Lecture [slides](https://docs.google.com/presentation/d/1qrKOtpO_ywEIyo-Iu8vvD0NSGfTr0GUY77Gg2nCDCvY/edit?usp=sharing)
A recent [review](https://doi.org/10.1016/j.cell.2024.04.037) on the role of mitochondria in health and disease

## Lecture 10. Disease risk calculations

February 13, 2025

[Lecture slides](https://docs.google.com/presentation/d/1BuUzBd9-kkiCo83n-VnEUt3wig75JTep7ujETyXbha8/edit?usp=sharing) on Google slides
[Problem set 4](https://docs.google.com/document/d/1vxjKRjIaE_OF9_QpFhC5IWcbrzRAq5hAJG3AyyzhoUo/edit?usp=sharing)
Problem set 4 [solutions](https://docs.google.com/document/d/1GrYfr59xRT2re0ZMn5W3wDFg2tNAHc1GwckBOJh7GvE/edit?usp=sharing)

## Lecture 11. Movie reflections

February 18, 2025

Watch movie "Three Identical Strangers" (2018) BEFORE CLASS

## Lecture 12. Presentations on mitochondrial mutations

February 20, 2025

[Rubric](https://docs.google.com/document/d/16Zlcb_EHkCpRscRaV4zAFkJn5heESkHzHsPe1YfCOEg/edit?usp=sharing)
[Rebolledo-Jaramillo et al. 2012](https://www.pnas.org/doi/abs/10.1073/pnas.1409328111?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed) - Group 1
[Zaidi et al. 2019](https://www.pnas.org/doi/abs/10.1073/pnas.1906331116?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed) and its [press release](https://www.bx.psu.edu/makova_lab/press_release/2019-11-18/) - Group 2
[Barrett et al. 2019](https://royalsocietypublishing.org/doi/full/10.1098/rstb.2019.0175?rfr_dat=cr_pub++0pubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org) - Group 3
[Arbeithuber et al. 2022](https://www.pnas.org/doi/abs/10.1073/pnas.2118740119?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed) and its [press release](https://www.bx.psu.edu/makova_lab/press_release/2022-04-04/) - Group 4

## Lecture 13. Multifactorial inheritance and complex disorders, Genome-Wide Association Studies (GWAS)

February 25, 2025

[Lecture slides](https://docs.google.com/presentation/d/1T4azRSRsOraUpKAHaLjyIJX7gv5m9hVHg_3gp5K2jbE/edit?usp=sharing) on Google slides

Paper: https://doi.org/10.1038/s41588-021-00986-w

## Lecture 14. Multifactorial inheritance and complex disorders, polygenic risk scores, examples

Fenruary 27, 2025

Lecture [slides](https://docs.google.com/presentation/d/1Lb6SoWjevktmnPs4radhoeJdbR0ZgduklRK5XqHGdHo/edit#slide=id.p) on Google slides
Our [manuscript](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9813976/) on constructing a polygenetic risk score for childhood obesity

## Lecture 15. In-class test

March 4, 2025

## Lecture 16. Omics data used to study diseases: An example of childhood obesity

March 6, 2025

[Lecture](https://www.youtube.com/watch?v=j8prICB3ZrI) on YouTube

## Lecture 17. Genetics and biology of aging

March 18, 2025

Lecture [slides](https://docs.google.com/presentation/d/15OGrmh5pZEin9KUsJTGh3OluR6t3Nrho3Dk-rc21e6c/edit?usp=sharing) on Google slides
A [paper](https://www.pnas.org/doi/full/10.1073/pnas.1902452116) about the relationship between the speed of telomere shortening and life span in different species
A [paper](https://genomebiology.biomedcentral.com/articles/10.1186/gb-2013-14-10-r115) by Horvath (2013) about epigenetic clocks
A [review](https://www.sciencedirect.com/science/article/pii/S0092867422013770?via%3Dihub) on hallmarks of aging
An [article](https://www.economist.com/technology-quarterly/2023/09/25/slowing-human-ageing-is-now-the-subject-of-serious-research) from Economist on aging

## Lecture 18. Ovarian aging and genetics of infertility

March 20, 2025

Lecture [slides](https://docs.google.com/presentation/d/1NvKI9VyjOqQCk-9-2FnxVABCUAOCI1U2HU1xUX-EJnk/edit?usp=sharing)
A [book](https://www.google.com/books/edition/Female_Biology/d0zpEAAAQBAJ?hl=en&gbpv=1&dq=female+biology&printsec=frontcover) on Female biology by Prof. Dever
A movie on egg freezing: https://www.youtube.com/watch?v=98R8ObXlR1E
A [paper](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611832/) on genetic causes of oocyte aging
A [review](https://academic.oup.com/humupd/article/27/1/154/5942726?login=true) on genetic causes of infertility
Overcoming infertility: a possibility of bipaternal offspring? A recent [paper](https://www.nature.com/articles/s41586-023-05834-x)
Evolution of menopause in toothed whales - a recent [paper](https://www.nature.com/articles/s41586-024-07159-9) and its [review](https://www.nature.com/articles/d41586-024-00794-2) in Nature
A new [paper] (https://www.nature.com/articles/d41586-024-02905-5) on early menopause

## Lecture 19. Aging: presentations

March 25, 2024

Reversible hair greying (a [paper](https://elifesciences.org/articles/70584))- group 1
Effects of rising temperatrures on aging - a [paper](https://www.science.org/doi/10.1126/sciadv.adr0616) and its [summary](https://www.news-medical.net/news/20250305/Extreme-heat-may-speed-up-aging.aspx) - group 2
Adults in mid-life experience less stress (a [paper](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9993073/) from PSU) - group 3
Protective role of parenting on brain aging - a [paper](https://www.pnas.org/doi/full/10.1073/pnas.2411245122) - group 4

## Lecture 20. Pharmacogenomics

March 27, 2025

Lecture [slides](https://docs.google.com/presentation/d/1eG-UE-OTugAmhPIdxVuKwk_0ezofvBpXu-OKiMOIYSU/edit#slide=id.g2286998593f_0_138)

## Lecture 21. Genetics of healthy pregnancy and prenatal testing

April 1, 2025

Lecture [slides](https://docs.google.com/presentation/d/1_Q7RivgcH8BdNMGqVNzNRhOPqvYuKv-1A2Ti-vPB-G4/edit?usp=sharing)
A [review](https://www.nature.com/articles/d41586-021-03801-y) and an original [paper](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8770117/) about pre-eclampsia testing using cell-free RNA
Toll on the woman's body after pregnancy: a recent [paper](https://www.science.org/doi/epdf/10.1126/sciadv.adr7922) and its short [version](https://www.nature.com/articles/d41586-025-00959-7?utm_source=Live+Audience&utm_campaign=06ad1f325c-nature-briefing-daily-20250327&utm_medium=email&utm_term=0_b27a691814-06ad1f325c-498731983)

## Lecture 22. Personalized medicine

April 3, 2025

Lecture [slides](https://docs.google.com/presentation/d/1fd0w9fyh7nPO1BM0O_xwf6WF8SPnMzD5ifwQrCQbysM/edit?usp=sharing)
An [article](https://www.scientificamerican.com/article/a-breakthrough-in-genetic-medicine-for-rare-diseases/) from Scientific American about antisense oligonucleotide treatment
A [video](https://youtu.be/F4niMKa0vtI?si=xE8jTOpUblQrUhIE) about gene therapy: from Genethon (France)
A Nature [review](https://www.nature.com/articles/s41392-023-01309-7) on CRISPRs
A New York Times [article](https://www.nytimes.com/2024/05/06/health/sickle-cell-cure-first.html?smid=nytcore-ios-share&referringSource=articleShare) on the use of CRISPR technology to treat sickle cell anemia
A [video](https://www.youtube.com/watch?v=ViUZyJ2EW1o) in which Leroy Hood discusses Phenome Health.
The [issue](https://phenomehealth.org/publications/scientific-america-the-new-science-of-wellness) of Scientific American on scientific wellness
A website of [PhenomeHealth](https://phenomehealth.org), a non-profit founded by Leroy Hood
Why is exercise good for you? A [paper](https://www.nature.com/articles/d41586-024-01200-7) in Nature
A [paper](https://www.science.org/doi/epdf/10.1126/science.adm9218) about practical challenges of precision medicine
Digital you: https://www.science.org/doi/10.1126/science.ads7922

## Lecture 23. Epigenetics and imprinting in disease. Environmental influences on the genome.

April 8, 2025

Lecture [slides](https://docs.google.com/presentation/d/1GxrniAh6fGR18jqhdhw84a9mNddjzDshhaWsFbtXFm8/edit?usp=sharing)
[Chapter](https://www.clinicalkey.com/#!/content/book/3-s2.0-B9780128125373000056?scrollTo=%23hl0000808) on epigenetics from Emery and Rimoin's Principles and Practice of Medical Genetics and Genomics
An [article](https://www.nature.com/articles/nsmb.2489) about epiogenetic reprogramming during development (Cantone & Fisher 2013, Nature)
A [preprint](https://www.biorxiv.org/content/10.1101/2023.01.13.523912v1) on father's preconception smoking and offspring DNA methylation
Makova Lab [preprint](https://pmc.ncbi.nlm.nih.gov/articles/PMC11268442/) on methylation with childhood obesity
X chromosome inactivation and cancer risk: a new [paper](https://www.nature.com/articles/s41588-024-01924-2)
A new [paper](https://www.nature.com/articles/d41586-025-00682-3) about the protective effects of the second X chromosome

## Lecture 24. Movie 2 reflections

April 10, 2025

## Lecture 25. Genetic counseling

April 15, 2025

Lecture [slides](https://docs.google.com/presentation/d/16iNlVsqCr0_unnaHX78WTHKuXe53vt9nEnrnSKfm_I4/edit?usp=sharing)
Clinical scenarios [questions and answers](https://docs.google.com/document/d/1akGxowFYM8Qk88v0ThADMmE5yIG-KfNnNsHy3WRLYes/edit?usp=sharing)
How common is non-paternity? A [paper](https://www.science.org/content/article/how-often-are-children-genetically-unrelated-their-presumed-fathers)

## Lecture 26. Test 2

April 17

## Lecture 27. Debate on ethical issues

Apr 22

Read pages 345-354 in your textbook.

Also read this paper: "[Money and murder](https://www.nature.com/articles/d41586-025-00457-w)"

## Lecture 28. Debate on legal issues

Apr 24

Listen to Digital you: https://www.science.org/doi/10.1126/science.ads7922

Read on [patenting human genes](https://www.aclu.org/news/privacy-technology/the-fight-to-take-back-our-genes) and [forensic genetic genealogy](https://www.scientificamerican.com/article/forensic-genealogy-offers-families-the-gift-of-closure/)

## Lecture 29. Cancer genomics

Apr 29

Lecture [slides](https://docs.google.com/presentation/d/1pCYxFJUZtw28ssWxvrWIr46Tfwai_wMFJlc8uxq0H3o/edit#slide=id.g22b6530a8ff_0_50)
An [article](https://www.sciencedirect.com/science/article/pii/S0753332219352837) on the mechanism of PARP inhibitors in treatment of ovarian cancer
A paper on BRCA1: https://www.nature.com/articles/d41586-024-03358-6#ref-CR1
A p53 [video](https://www.youtube.com/watch?v=_Isvd01XvSs)
A recent [paper](https://www.cell.com/cell/pdf/S0092-8674(24)00246-0.pdf) about p53
An [article](https://www.nytimes.com/2013/05/14/opinion/my-medical-choice.html) by Angelina Jolie who decided to have a double mastectomy because of her high risk of breast cancer
A [paper](https://aacrjournals.org/cancerdiscovery/article/12/1/31/675608/Hallmarks-of-Cancer-New-DimensionsHallmarks-of) on the hallmarks of cancer

## Lecture 30. Sex predisposition to diseases

A Nature [paper](https://www.nature.com/articles/d41586-024-01204-3) on the complexities surrounding the concepts of gender and sex
A [manuscript](https://doi.org/10.1016/j.cell.2022.04.012) on the role of sex and gender in cardiovascular diseases
A [paper](https://www.science.org/doi/10.1126/sciadv.adk1487) on why there are differences in blood pressure between men and women
A [manuscript](https://www.nature.com/articles/d41586-021-01836-9) on importance of sex in autoimmune diseases
Another [paper](https://www.nature.com/articles/d41586-024-00267-6) about why autoimmune diseases are more prevalent in females