sulogo Matematiska institutionen

Stockholms universitet
Brunnsviken

Under a Nordplus programme, starting Fall 2007, the Universities of Stockholm, Oslo, Helsinki and Copenhagen jointly organize a set of Master level courses in Biostatistics. The Universities in Newcastle and Gent also take part in this collaboration. Master- and Phd-students from the collaborating universities as well as from other universities are welcome to participate. The second of these courses is on Population genetics and gene mapping at Stockholm University (see below for a detailed program.):

BMC2: Population genetics and gene mapping

 Mathematical Statistics,
Stockholm University

Changes of human DNA over time is a combination of random inheritance (Mendelian laws), recombination of maternal and paternal DNA, mutations and selection principles. This is conveniently described using tools from probability theory and stochastic processes. The population genetic models so obtained are important for understanding variation of DNA between individuals and populations. This in turn has applications for 1) human ancestry and estimating age of populations 2) locating genes that increase risk for inheritable diseases (gene mapping). The course will focus on mathematical and statistical principles of population genetics and gene mapping. We present concepts of molecular genetics and discuss population genetic models, coalescent theory, familial aggregation, segregation analysis, linkage analysis, testing of candidate gene associations, genome-wide association and linkage disequilibrium mapping.



Faculty


Professor Juni Palmgren,
Mathematical Statistics,
Dept of Mathematics,
Stockholm University.
House 6, Room 329,
email: juni@math.su.se,
Phone: +46-8-164557

 

Professor Ola Hössjer,
Mathematical Statistics,
Dept of Mathematics,
Stockholm University.
House 6, Room 322,
email: ola@math.su.se,
Phone: +46-8-164584



Goals

  1. To understand the structure of chromosomes and DNA, the process of cell division, genetic recombination, transcription and translation

  2. To understand the basic forces in population genetics and be able to dress them as probability models

  3. To understand the rationale for genetic linkage and association studies, to be able to critically evaluate and choose between designs and to perform and interpret analyses

Goals are addressed through lectures, seminars, homework and a course project.

Course literature

Articles, lecture notes and assignments will be handed out. We will refer to the books 1 and 2 below, but it is optional to buy them.

  • Thomas, D. (2004). Statistical Methods in Genetic Epidemiology. Oxford University Press. ISBN 0-19-515939-X

Thomas' book provides a broad overview aimed at bridging the field of epidemiology, statistics and human genetics. It covers the statistical methods used in familial aggregation, segregation analysis and linkage analysis and proceeds to introduce the basic population genetics principles on which studies of genetic association and linkage disequilibrium rely.

  • Hein, J., Schierup, M.H. and Wiuf, C. (2005). Gene genealogies, variation and evolution. Oxford University Press, Oxford. ISBN 0-19-852996-1 (paperback).

This is an elementary, yet strict, book on coalescent theory. It gives theoretical insight into forces underlying human evolution and association mapping. The basic coalescent (based on the Wright-Fisher model of reproduction) is extended to allow for population size changes, population structure, various forms of selection and recombination. The use of coalescent theory for association mapping is also treated.

The books by Thomas and by Hein et al. cover the course content. The topics of genetic epidemiology and population genetics/coalescent theory come together when dealing with linkage disequilibrium structure and fine scale association mapping. The following books are complementary:

  • Ziegler, Andreas and König, Inke. A statistical approach to genetic epidemiology. Wiley 2006. ISBN 978-3-527-31252.

  • Durrett, R. (2002). Probability Models for DNA Sequence Evolution. Springer, New York. ISBN 0-387-95435-X.

Credits and marking

Active participation during course weeks in Stockholm together with successful assignments and project exam gives 7.5 ECTS credits. The marking is made according the 6-level goal oriented scale (A: Excellent B: Very Good C: Good D: Acceptable E: Sufficient F: Insufficient), with the first five indicating pass

Schedule

Section 1: Introductory reading at home university.

You should familiarize yourself with the following material before arriving in Stockholm January 14. Note, that you need not have grasped all details, much of it will be repeated and explained during the course, but you do need to have an idea of the topics.

MCJ Dekker and CM van Duijn. Prospects of genetic epidemiology in the 21st century. European Journal of Epidemiology 2003; 18:607-616. (can be downloaded in pdf format).

Chapter 5 in Almgren, Bendahl, Bengtsson, Hössjer, Perfect: Statistics in Genetics, Lecture Notes. Lund University, Centre for Mathematical Sciences, Mathematical Statistics, November 2003. (can be downloaded in pdf format).

Nordborg M. Coalescent Theory. In Handbook of Statistical Genetics (Edited D.J.Balding, M. Bishop, C. Cannings). John Wiley 2001; 179-212. (can be downloaded in pdf format)

Section 2: Lectures 14 - 18 January at Stockholm University

Section 2 covers concepts of genetics, familial aggregation, segregation, linkage and association analysis.

It starts on Monday January 14 with lectures from 1-4 pm (see location below). Tuesday-Friday there will be lectures in the morning 9-12 am and Tuesday-Thursday seminars in the afternoon 2-4 pm. The week ends on Friday at noon.

The seminars will be in the form of paper discussions, requiring preparation during time out of class. Students will be asked to present papers and to actively query and discuss their content. Seminar activity will be evaluated with a weight of 15% of the total mark of the entire course.

Additional material for Section 2

Section 3: Homework at the home university

Assignments will be handed out at the end of the Section 2 course week. They should be sent in to Ola Hössjer (ola@math.su.se) by 4 February. Assignments will be evaluated with a weight of 35% of the total mark.

Here is home assignment 1 with deadline 4 February. This was changed 28 January, because of an error in Exercise 2, the two lines below equation (2).

Section 4: Lectures 11 - 15 February at Stockholm University

Section 4 covers the basics of population genetics, coalescent theory and the rationale and conduct of genome-wide association scans (GWAS). The schedule is similar to that of Section 2. Seminar activity is given a weight of 15% of the total mark.

Additonal material for Section 4

Section 5: Project exam at the home university.

Projects will be handed out at the end of the Section 4 course week. They should be sent to Juni Palmgren (juni@math.su.se) by March 7. The project exam will be evaluated with a weight of 35% of the total mark.

Additional material for section 5: Project

Venue

Lectures will take place in Room 16, House 5, Dept of Mathematics, Stockholm University. For detailed information on the venue, including map, see www.math.su.se

Accomodation

Participants are asked to arrange for their own accommodation. Below we give suggestions for hostels and hotels:







Photos

Here are some photos from this course.