Cystic Fibrosis (CF) - gene location

Cystic Fibrosis (CF): Molecular defect

Cystic Fibrosis (CF): One gene may lead to many phenotypic effects

Cystic Fibrosis lungs Normal lung Lung from a CF patient, showing extensive destruction as a result of obstruction and infection

Normal pancreas CF Pancreas showing infiltration of fat and fibrotic lesions Cystic Fibrosis Pancreas

Tay Sachs Defective enzyme that breaks down a particular fatty substance

ALPHA GLOBIN BETA GLOBIN Sickle cell mutation Heme Iron atom Heme Iron atom Sickle cell mutation 9 The hemoglobin tetramer

Normal and Sickled Cell 10

Sickle Cell Anemia (AR) Aggregation of hemoglobin molecules. Mutant hemoglobin molecules in red cells stack to form rodlike structures, which causes the red cells to deform.

The Genetics of Cancer

Fig Signaling cell DNA Nucleus Transcription factor (activated) Signaling molecule Plasma membrane Receptor protein Relay proteins Transcription mRNA New protein Translation Target cell Signal Transduction: How a cell can respond to signals from its environment Results in a change in which genes are expressed (turned on)

Fig a Growth factor Protein that Stimulates cell division Translation Nucleus DNA Target cell Normal product of ras gene Receptor Relay proteins Transcription factor (activated) Hyperactive relay protein (product of ras oncogene) issues signals on its own Transcription Ras is an oncogene (cancer gene) the normal form of the gene is called a proto- oncogene Oncogenes STIMULATE cell division

Fig a Mutation within the gene Hyperactive growth- stimulating protein in normal amount Proto-oncogene DNA Multiple copies of the gene Gene moved to new DNA locus, under new controls Oncogene New promoter Normal growth- stimulating protein in excess Normal growth- stimulating protein in excess

Fig b Growth-inhibiting factor Protein that inhibits cell division Translation Normal product of p53 gene Receptor Relay proteins Transcription factor (activated) Nonfunctional transcription factor (product of faulty p53 tumor-suppressor gene) cannot trigger transcription Transcription Protein absent (cell division not inhibited) Normal tumor- suppressor genes prohibit cell division

Fig b Mutated tumor-suppressor gene Tumor-suppressor gene Defective, nonfunctioning protein Normal growth- inhibiting protein Cell division under control Cell division not under control

18

Both alleles of BRCA1 or both alleles of BRCA2 must be mutant for cancer to develop. Why would in follow a dominant inheritance pattern? A tissue comprised of billions of cells heterozygous for BRCA1 or BRCA2 20 Your (my) probability of winning the lottery is very small. The probability that someone will win it is very large.