Biostatistics 666: Introductory Lecture

Objective

This lecture introduces course objectives, which are to provide students with a working understanding of the techniques commonly used by statistical geneticists. These techniques can server as building blocks for the implementation of more complex, customized analyses. In addition, the lecture provides a brief overview of some of the key questions that statistical genetics tries to answer.

There are two important sets of questions...

Describing Genetic Variation

• One set of questions concerns the description and characterization of genetic data in the population. This will include estimation of allele and haplotype frequencies, tests of Hardy-Weinberg equilibrium, reconstruction of DNA sequences using small, fragmentary sequences as input. These analyses are an essential step in the quality control and assessment of any genetic dataset and a necessary and important first step in the analysis of any dataset.

Connecting Genetic Variation to Phenotype

• Another key, and perhaps more interesting, set of questions concerns those that help clarify the relationship between DNA sequences and biological outcomes, including human disease but also a variety of other traits. This second set of questions can conveniently be grouped into three:

1. Are there genes influencing the trait of interest? This sort of evidence can be investigated in twin and family studies, for example, by examining if close relatives (such as identical twins) show outcomes that are more similar than those of more distant relatives (such as fraternal twins).
2. Where are the genetic variants that influence a trait? These types of analysis try to assign a specific chromosomal location to the variants that influence the trait. Traditionally, this step relied on linkage analysis but association analysis and related approaches are now more common.
3. What are the specific variants that influence a trait? This is, ultimately, the most interesting question but is often the hardest questions to answer. It requires exhaustive measurement of DNA variation in a region of interest and, often, comparison of results across different populations and follow-up laboratory experiments.

Recommended Reading

If you need a refresher or introduction to molecular genetics, I recommend:

Human Molecular Genetics by Tom Strachan and Andrew Read Web Edition at NCBI

Lander and Schork (1994) "Genetic Dissection of Complex Traits" Science 265:2037-48 PDF at Science Magazine

Slides

Slides in PDF Format