What makes us unique. Changes in the number and

order of genes (A–D) add variety to the human genome

Inversion Insertion

Deletion Copy number variation

Reference

http://www.sciencemag.org/cgi/reprint/318/5858/1842.pdf

There are variations in genesthat make us unique

Genes can have variation that does not necessarily cause disease. These variations

may have an effect on how much protein it produced or how well that protein works.

In an otherwise healthy person, this variation may

have little or no effect. In a person with a disease like CF, this variation may modify the severity of the CF symptoms.

Genes that modify CF symptoms are called

modifier genes.

NOW WE UNDERSTAND THE ROLE OF CFTR…

WHAT ABOUT GENES THAT MODIFY CF?

The CF Twin and Sibling Study is looking for

genetic variation that is linked with CF. It is

important that we study families, not just

individuals diagnosed with CF. If we know the

parent’s genetic variation, we can then

study what combinations of genetic variation they give to their children.

We also examine what genetic variation siblings do and do not share. We

then compare the genetic variation with

symptoms. Where these pieces of information line up in

the family (shared variations and shared

symptoms) give clues for genes that may affect CF

disease.

Intra-pair Comparison: Monozygous Twins

10

30

50

70

90

11

013

0%

FE

V1

10 30 50 70 90 110 130%FEV1

N = 30Mean Age = 18.7r = 0.84Slope = 0.80St. Dev = 9.75

CF patients live in their own unique

environments (smoking, diet, and exposure to

pollutants). Using families also helps us

sort out which CF symptom differences are

caused by genetic factors, caused by

environmental factors, or caused by a

combination of genes and environment.

www.sph.umich.edu/.../fall07/inFOCUS/four.htm www.sph.umich.edu/.../fall07/inFOCUS/four.htm www.sph.umich.edu/.../fall07/inFOCUS/four.htm

www.sph.umich.edu/.../fall07/inFOCUS/four.htm

Finding other genes (like the ones that

effect Diabetes, BMI, Lung Disease) will help us to understand why symptoms

happen and help us to predict those symptoms. We can then design

treatments or medicines based on personal risks.

The FutureIndividuals respond differently to drugs

and sometimes the effects are unpredictable. Differences in DNA…targeted by drugs can contribute significantly to variation in the

responses of individuals… This intersection of genomics and medicine has the potential to yield a new set of molecular diagnostic tools

that can be used to individualize and optimize drug therapy.

William E. Evans and Mary V. Relling. Moving towards individualized medicine with pharmacogenomics. Nature 429, 464-468 (27 May 2004)