Introduction to human genetics

Interphase nucleus and metaphase human chromosomes with centromeres stained yellow.

Instructor: Stefan Surzycki

Course Requirement: A course in genetics or consent of instructor

Goals

The human genome is of great interest and is the subject of intensive basic and applied research. This field of genetics is one of the most rapidly growing areas of biology today. The goal of the course is to introduce students to human genetics, with an emphasis on its applications to medicine, genetic counseling and forensic analysis. The focus of the course will be on new developments in the field afforded by present day techniques in molecular biology and the completion of sequencing the human genome. The course will permit you to learn basic principles used in analysis of human genes, the structure of the human genome and the molecular basis of many human diseases.

Among the topics considered will be:

· Fundamentals of transmission genetics, pedigree analysis of inheritance of dominant and recessive genes. Linkage analysis (linkage disequilibrium and lod score analysis). Sex linked inheritance; sex influenced and sex limited inheritance. Determination of sex in humans.

· Fundamentals of human genome structure. Gene and chromosome structures.

· Organization and expression of the human genes. Human multigene families.

· Human repetitive DNA, VNTR analysis, mini and microsatelites. DNA fingerprinting.

· Mutation and instability of human DNA. Chromosomal abnormalities.

· Mapping of the human genome. Physical mapping, genetic mapping. Human Genome Project. SNP mapping.

· Human genetic diseases. Molecular pathology of most common genetic diseases. Complex diseases. Genetic testing.

· Gene therapy and novel therapeutic approaches to human genetic abnormalities.

· Genetics of cancer. Oncogenes and tumor suppressor genes.

Course Format.

The course will be presented in a lecture format, with coverage of topics arranged as outlined in the attached draft, course lecture schedule.

Course Requirements.

Students will be responsible for understanding the material presented in the lectures and material assigned from Internet as well as from the textbook. Since lectures are the main source of recent material, students are expected to attend each class meeting (although attendance will not be "taken"), except in the event of legitimate medical or family emergencies.

Course Grading.

The progression of each student's understanding of the course material will be assessed using two written examinations and 10 home assignments in the form of written reports.

Take home report subjects are:

· Genetic problems.

· Work on internet with human genes DB.

Each exam will contribute 25% to the final grade (total 50%).

Reports will contribute remaining 50% of the final grade.

Lectures Outline

	Lecture 1. Introduction to the course. Organization. Human genetics on internet.
	Lecture 2. Review of basic concepts of genetics. Compound heterozygote, Multiple alleles. Dominance and codominance. Penetrance and expressivity. Allelic heterogeneity. Locus heterogeneity. Human genes nomenclature.
	Lecture 3. Human genetics methodology: Pedigree analysis. Pedigree analysis of autosomal recessive inheritance. Carriers. Molecular mechanisms of some recessive disorders.
	Lecture 4. Autosomal recessive diseases in population. Hardy-Weinberg equilibrium. Gene frequencies. Ratio of carriers to affected. Heterozygotic advantage and gene frequency in population.
	Lecture 5. Autosomal dominant inheritance. Penetrance and variable expression. Late onset expression. Pleiotropy and phenocopies. Molecular basis of dominant inheritance. Description of gene: genomic genotype, genomic complexity, genetic phenotype, physiological phenotype.
	Lecture 6. Beyond pedigree analysis. Bias of ascertainment for dominant and recessive traits. Quantitative trait. Complex traits. The spectrum of human characters. Anticipation and imprinting.
	Lecture 7. Sex linked inheritance. Examples of dominant and recessive genes. Hollandric inheritance.
	Lecture 8. Genetic counseling using Bayes’ statistic.
	Lecture 9. Linkage analysis. Parametric and non-parametric meiotic mapping methods. Lod analysis.
	Lecture 10. Allele sharing. Linkage disequilibrium analysis (LD). Application of LD in human genetics. Allelic association.
	Lecture 11. Linkage disequilibrium analysis and human genome evolution.
	Exam I
	Lecture 12. Discussion of exam results. Human genome organization.
	Lecture 13. Human repetitive DNA. Human tandem repeated DNA. Satellite DNA, minisatellite DNA and microsatellite DNA. VNTR sequences and DNA fingerprinting.
	Lecture 14. Structure and function of telomeric DNA.
	Lecture 15. Interspersed repetitive DNA (SINE and LINES). Role of SINE and LINE in human genome evolution. Human genome polymorphism. SNP polymorphism and its practical applications.
	Lecture 16. Structure of human genes. CpG islands. Expression of human genes. Gene and gene families. Examples of gene families (globin and retinal visual pigments genes).
	Lecture 17. Morphology of human chromosomes. Chromosome banding. Sex chromosomes organization. Classification of genes present on sex chromosomes.
	Lecture 18. Molecular basis of sex determination. Chromosome X inactivation. Dosage compensation. XIC function.
	Lecture 19. Mutations of human genome. Classification of mutations. Chromosomal aberrations in humans. Abnormal chromosome number. Sex chromosomes and their abnormalities. Nondisjunction.
	Lecture 20. Abnormal chromosome structure (deletions, duplications, inversions, translocations). Balanced translocation.
	Lecture 21. Down syndrome. Classes of point mutations.
	Lecture 22. Molecular mechanism of point mutations. DNA damage and error of replication. Mutation rates in male and female. Somatic mutations.
	Thanksgiving Recess
	Lecture 23. Molecular mechanism of point mutations. Trinucleotide repeat mutations.
	Lecture 24. Structure and inheritance of mitochondrial DNA. Mitochondrial diseases. Mitochondrial DNA as a tool to study human origin. Seven daughters of Eve.
	Lecture 25. Oncogenes in humans. Molecular basis of cancer. Cloning of human oncogenes. Classification of oncogenes. Cancer suppressor genes.
	Lecture 26. Oncogenesis. Colon cancer and breast cancer. Cancer therapy.
	Exam II

Human chromosomes hybridized with chromosome painting probes.

The Pharaoh Tutankhamun showing features often found in Kleinfelter Syndrome. These people are phenotypically male with two X and one Y chromosomes (47,XXY). This abnormality occurs about once in 1000 births.

Results of DNA fingerprinting using the 33.1 VNTR probe. M- mother DNA; C- child DNA; F1 and F2 DNA of presumed fathers.