Biology Dept.

DePauw University

Spring 2016
Instructor: Fornari

BIO 415 Lecture

Molecular Genetics

Lecture-MWF 1:40-2:40
in Olin 136

Instructor: Chet Fornari
Olin 232, x4781; e-mail: cfornari

Please Note: this course is an elective for Biology and Biochemistry Majors

Instructor: Chet Fornari
Olin 232, x4781; e-mail: cfornari


Text: Genetics & Genomics in Medicine (2015), by Tom Strachan;
Garland Science Publishers (ISBN: 978-0-8153-4480-3)

Other texts used as resources (not required): Human Molecular Genetics (2011, 4th ed.) by Stachan and Read;
Human Genetics and Genomics (2013, 4th ed.) by Korf and Irons;
Genetics in Medicine (2016, 8th ed.) by Thompson & Thompson;
Genetic Counseling Research: A Practical Guide (2014) by MacFarlane, Veach & Leroy;
Bioinformatics and Functional Genomics (text used for Bio325 Bioinformatics course; (2015, 2nd ed.);
Junk DNA: a journey through the Dark Matter of the Genome (2015) by Nessa Carey

Prerequisites: BIO101, CHEM240; BIO315 recommended, or instructor's permission

Brief Outline of Course Contents:

I. Chromosome Structure/Function & Ideograms; some basic Transmission Genetics, Linkage & Mapping for Human pedigrees; Essentials of the Human Genome; Introduction to Relevant Web-sites (UCSC and NCBI and Ensembl)


II. Organizaton, structure, function of the Human Genome by the ENCODE Project and its Explorer; Discovering Human Disease Genes by Integrated Mapping and Bioinformatics of large data sets ('reverse' genetics) - Advanced Human Genome; some baic Quantitative & Population Genetics
III. An examination of the popular 23andMe service and its use of SNPs (or TASs) for ancestry and medical diagnostics; risk assessment in correlating SNPs with disease predictions
IV. Genetic Diseases & Molecular Pathology; The molecular genetics of selected diseases, diagnostics, treatments.

"Science should be as simple as possible but not simpler."
--Albert Einstein

Description of Course Contents

Part I of the course focuses on (a) the Human Genome, (b) the structure, function & transmission of genes and chromosomes, along with (c) an introduction to DNA polymorphisms and variants. Essentially we will 'deconstruct' the human genome cytogenetically, structurally, and functionally with the ultimate goal of explaining the origins, biochemistries, and treatments of human diseases. We study basic genetics and the human genome early in the semester to facilitate better understanding of more advanced topics that relate to disease. So it's important to master this information at the start of the semester. Also, we will try to appreciate more fully the strong connections between the development and use of methods (biochemical, genetic, ctyogenetic, and computational), and the generation of data to support or refute creative hypotheses. All computational or bioinformatic methods and procedures are presented as ways to develop skills in accessing and understanding data and annotated information rather than in learning how to become a bioinformatician; see this link for further comment.

Part II of the course focuses more deeply on the Human Genome, and serves to direct our attention to the genes and gene families in our genome that are ultimately responsible for disease (both 'simple' and 'complex' diseases). In this section we explore fully the ENCODE Project Consortium and its discovery of a dynamic human genome, in stark contrast to previous estimates of "junk DNA". The ENCODE project's results and extensive data sets provide a deep look into this "junk DNA" and reveal instead a transciptionally and functionally active genome, with direct implications for disease (in concert with epigenetics and the Epigenome - HEP for Human Epigenome Project). We will also review a few, classic disease genes with their associated simple and complex syndromes, and examine especially the genetic variants (SNPs to CNVs to Structural) contributing to disease and pahtology.

Part III focuses on the underlying genetic theory and practice of the popular 23andMe service for assessing ancestry and disease risks associated with SNP patterns in individual genomes.

The last part of the course (Part IV) presents modern Medical Genetics and Molecular Pathology; we will examine the history and genetic causes of certain diseases, and relate this scientific endeavor back to the Human Genome Project and the ENCODE Project and its UCSC page (also available from European Bioinformatics Intitute's Ensembl).

Throughout the course, we will emphasize experimentation and bioinformtics as the primary means of generating and validating data to test hypotheses; so we will examine the theoretical basis for a some key methods. Understanding these methods facilitates the development of skills in designing a good experiment, or critically evaluating the data in a journal article, or diagnosing a particular constellation of symptoms as a specific disease. Information and discussions from both the lecture and lab will help you to become thoroughly familiar with some of these basic techniques and concepts.

{Current Reading Assignments and Problems or CRAaP}

Specific topics, with Chapter references (specific page assignments provided in lecture)*:

*Please note: we will not follow chapters in a 'lock-step' fashion, but use them in any order to serve best the goals of the course (and see the inside, front cover of your text for some examples). In addtion, the course is based primarily on published articles (both primary and secondary, such as Scientific American, Scitables-Nature, Wiley's eLS, The Scientist, Annual Reviews, Nature Reviews), and the text serves as our reference for pursuing important topics in more detail with fuller, supporting explanations).


Topics in Sections (to be adapted to new text)

Part I - Chromosome Structure/Function & Ideograms; Transmission Genetics, Linkage & Mapping, Human pedigrees; Essentials of the Human Genome

1. Review as needed: basic review of eukaryotic gene structure, function, & expression (Central Dogma)
Chromosome Structure and Function
Genes in Pedigrees and Populations; The Genetic System: Mendel's Laws & Linkage (with emphasis on Human Pedigrees); complications with the 'simple' Mendelian pedigrees
4. Genetic Mapping of Mendelian Characters; single-gene disorders and diseases
5. Nature and Mapping of Genes for Complex Diseases; Common Disease Common Variant Hypothesis



Biochemical Methods used in Cloning, Genomics, and Human Genetics

6. Selected Topics, only as needed to understand critical methods (ChiP-seq for example)


Part II - Organizaton of the Human Genome; Discovering Human Disease Genes by Integrated Mapping and Bioinformatics - Advanced Human Genome; Bioinformatics; Population Genetics

7. Organization and Structure of the Human Genome
8. Comparative Genomics; gene and genome Evoltion
9. Studying gene function;
bioinformatics: Genomics, Functional Genomics, & Proteomics: DiseaseGeneLinks;
10. Identifying Human Disease Genes; 8 examples



Part III - Genetic Diseases & Molecular Pathology

11.DNA-based diagnosis of genetic diseases; identifying human disese genes, cont'd.
12. Genetically complex human diseases; roles of common and rare variants.
13. Working toward human gene therapy; biochemical and genetic approaches.

Grading policies:
Grades are based on your completion of a series of Multiple Point Assignments (MuPAs), and a project when the course is offered with a lab. No exams are scheduled during the semester.

top of page

INTERNET SITES & JOURNAL ARTICLES for this course by section: (see lab syllabus for additional sites)

relevant web sites
sample journal articles

UCSC Genome Bioinformatics

Ensembl Human

Entrez Genome Project


GenePalette (requires program installation and registration)


Chromosome Mapping with DNA Markers by R. White & J-M Lalouel in Sci Am 258 #2 Feb 1988 (a classic paper that presents the essentials of classic genetics)

Selected SCIENTIFIC AMERICAN articles with referenced sections from primary literature articles, such as: From Atoms to Traits by David Kingsley 2009; What Makes Us Human by Katherine Pollard 2010; Desperate for an Autism Cure by Nancy Shute 2010; How We Are Evolving by Jonathan Pritchard 2010; Revolution Postponed by Stephen Hall 2010

REVIEW ARTICLE: The Genetics of Autism by R. Muhle, S.V. Trentaoste, and I. Rapin, MD in May 2004 Pediactrics 113 #5

REVIEW ARTICLE: The Melanocortin 1 Receptor (MC1R): More Than Just Red Hair by J.L. Rees in Pigment Cell Research 13: 135-140 (2000)


Short Tandem Repeat DNA Internet Database

The Biology Project: STR polymorphisms

Beckman-Coulter CEQ Sequencer: STR Genetic Analysis

Revisit second half of: Chromosome Mapping with DNA Markers by R. White & J-M Lalouel in Sci Am 258 #2 Feb 1988

REVIEW ARTICLE: Structural Variation in the Human Genome and its Role in Disease, P. Stankiewicz and J. Lupski, in Annual Reviews, 2010, vol. 61:437-55

REVIEW ARTICLE: Human Genome Project: Importance in Clinical Genetics, P. Little and R. Williams, in Wiley's eLS 2008



MedGen at NCBI

Ensembl's Diseases and Phenotypes

Genetic determinants of ulcerative colitis include the ECM1 locus and five loci implicated in Crohn's disease, in Nature Genetics vol. 40(6), 710-712 (2008)

Genetic Basis of Cancer

Cold Spring Harbor Laboratory


Sci Am article: Friction over Function - Scientists Clash on the Meaning of ENCODE's Genetic Data (2013); two articles by Sean Eddy to clarify the controversey
Sci Am article on Herceptin and Dimercept, May 2006
Sci Am articles with referenced sections of primary literature articles on How Cancer Arises
Sci AM article on the Genetic Basis of Cancer