Lecture 25: Beyond CSI I: Genetic Markers for diseases

(version 15 Apil 2008)

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Over the last ten years or so, a large number of DNA-based ``tests'' for disease risk have been developed. Here we discuss (i) how these are found, (ii) what they mean, and (iii) social implications.

The Genetics of Human Disease

Can score individuals as affected / unaffected. For example, you either have cancer or you don't

Alternatively, if known, the appropriate underlying physiological variable can be used as a quantitative character

e.g., Blood pressure vs. hypertension (affected / normal)

In most cases, don't know underlying biochemical variables.

Mapping genes underlying complex traits

Candidate locus approach

One looks for associations between the trait and the average values for particular alleles at the candidate locus

Example: Apo E (Apolioprotein E gene)

Example: D4 dopamine receptor (D4DR)

Marker-trait associations

The problem with the candidate-gene approach is that we have to have candidates! What if we don't? Use marker-trait associations

Breast Cancer: BRCA 1 and BRCA 2

Breast cancer


BRCA 1: Women who carry a mutation in the BRCA1 gene have an 80% risk of breast cancer and a 40% risk of ovarian cancer by the age of 70 years

BRCA 2: In addition to breast cancer in men and women, mutations in BRCA2 also lead to an increased risk of ovarian, prostate, and pancreatic cancers.

women with an altered BRCA1 or BRCA2 gene are 3 to 7 times more likely to develop breast cancer than women without alterations in those genes

Among individuals of Ashkenazi Jewish descent, researchers have found that about 2.3 percent (23 out of 1,000 persons) have an altered BRCA1 or BRCA2 gene. This frequency is about 5 times higher than that of the general population.