Learning Labs:   Molecular Biology

Cystic Fibrosis Prenatal Screening

Cystic Fibrosis Lab

Cystic fibrosis is the most common
serious genetic disease

Alex - The Life of a Child
by Frank DeFord

1983, 1997
RUTLEDGE HILL PRESS

211 Seventh Avenue No.
Nashville, TN

ISBN 1-55853-552-7

The American College of Obstetrics and Gynecology recommends that DNA testing for cystic fibrosis be offered to all couples ...
Cystic fibrosis (CF) occurs in 1 in 2500 live births in the USA, and a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene is carried by 1 in 25 people of northern European descent. Because the condition has serious consequences, causing progressive lung disease that is fatal in the vast majority of affected individuals by age 40, it is a candidate for prenatal screening. CF occurs as a result of mutations in the CFTR gene. The discovery and isolation of the CFTR gene made DNA testing for CF feasible.  The Foundation for Blood Research made important contributions to research and planning for DNA screening of CF mutations during pregnancy. This research led to the American College of Obstetrics and Gynecology recommending to all their members that testing for CF be offered to all pregnant couples. In the ScienceWorks lab, students are introduced to the concept of population screening and learn how DNA testing for the multiple common mutations in the CFTR gene is performed.

The significant ethical implications of screening for CF are highlighted by readings from Frank DeFord's book, Alex: The Life of a Child and by student role playing in a genetic counseling session following positive test results. Readings from DeFord's book illustrate the medical and emotional difficulties associated with CF. The role playing demonstrates the challenges couples confront following a positive screeing test result.

DNA ELECTROPHORESIS: CF Mutation Testing

Multiple mutation testing as performed in the FBR's Molecular Genetics Laboratory is simulated in this lab. The ARMS technique (Amplification Refractory Mutation System), also known as allele-specific polymerase chain reaction (PCR), is the method used. For the most common CFTR mutation, termed delta-F508, a phenylalanine at position 508 in the CFTR mutation is lost. This is due to the deletion of bases CTT as shown at the right. By designing a PCR primer with a sequence complementary to the sequence for the mutation, a PCR product is produced when the mutation is present, and no PCR product is produced when the mutation is not present.

This learning lab includes a simulation of the DNA electrophoresis that would be performed on the ARMS PCR product. Students learn to identify the delta-F508 mutation.

BIOINFORMATICS AND HUMAN GENOME DATABASES

As part of the class visit, we also introduce students to bioinformatics and "in silico PCR" - a way of probing gene sequences online using the primers for the delta-F508 region of the CFTR gene.