Moving forward

1972 Kerr, Wyllie and Currie Laterendonucleases and flippases

flippase

Observations Molecular players

(e.g. proteins and enzymes)

Moving forward
Take a genetic approach!
Look for individuals in a population that look or differently

Mutation change to the DNA of an individual Genotype the genetic makeup of an individual Phenotype traits that result from an individuals genotype
mutation

Cancer genetics

normal controlled cell proliferation

Cancer genetics
Cancer is an uncontrolled proliferation of cells
caused by mutations in the DNA of a cell (or small population of cells)
tumorigenesis

mutations

abnormal uncontrolled cell proliferation

Cancer genetics
Somatic mutation
occur anywhere in the body, except germ cells cannot be passed on to offspring

Germ line mutation

occur in germ cells can be passed on to offspring, where the mutation will be present in every cell

Follicular lymphoma

Lymphatic System
Tonsil Thymus

Important component of the immune system Lymph nodes

filter out foreign particles packed with immune cells

Spleen Lymph nodes

Lymphatic vessels

Lymphatic vessels

Lymphatic System
Tonsil Thymus

Important component of the immune system Lymph nodes

filter out foreign particles packed with immune cells

Spleen Lymph nodes

Lymphatic vessels

Lymphatic vessels

tonsils

thymus

bone marrow

spleen

LYMPHOMA
white blood cancer

B-cells T-cells

invade specific organs of the lymphatic system

lymph nodes

spleen

FOLLICULAR LYMPHOMA
white blood cancer
lymph nodes

B-cells

invade specific organs of the lymphatic system

lymph nodes

spleen

spleen

FOLLICULAR LYMPHOMA
white blood cancer

8 0% 1980s
specific change in the DNA
occurring in numerous patients

B-cells

invade specific organs of the lymphatic system

lymph nodes

spleen

Follicular lymphoma
t(14:18) translocation event

14
B-cell

18

Follicular lymphoma
t(14:18) translocation event
Chromosome 18

B-cell

Chromosome 14

What are chromosomes?

Humans have 23 pairs of chromosomes
large pieces of DNA contain information for making proteins information packaged into genes

What are chromosomes?

Humans have 23 pairs of chromosomes
large pieces of DNA contain information for making proteins information packaged into genes

Humans have ~25,000 genes

one gene one (or more) protein(s)

What is a gene?

What is a gene?
transcription unit

Part of the gene that is transcribed from DNA into RNA

What is a gene?
exons

Exons are included in the mature mRNA

exon

What is a gene?
introns

Introns are excluded from the mature mRNA

exon

intron

What is a gene?
(untranslated regions)

UTRs

5 UTR

3 UTR

Important for stability and localization of the mRNA

exon

intron

UTR

What is a gene?

pre-mRNA mRNA
processing export translation

protein

exon

intron

UTR

What is a gene?
promoter

Site where transcription machinery can dock

exon

intron

UTR

promoter

What is a gene?
promoter

protein

Site where transcription machinery can dock

exon

intron

UTR

promoter

What is a gene?
enhancer
(cis-regulatory element)

Proteins can bind to enhancers and activate transcription machinery

exon

intron

UTR

promoter

enhancer

What is a gene?
silencer
(cis-regulatory element)

Proteins can bind to silencers and block transcription machinery

exon

intron

UTR

promoter

enhancer

silencer

What is a gene?
upstream downstream

Enhancers and silencers determine the expression pattern of a gene. They can be located far away from the transcription unit.

exon

intron

UTR

promoter

enhancer

silencer

What is a gene?
exon intron UTR promoter enhancer silencer

Transcription unit

cis-regulatory elements

Gene