Mosaic screens Reading: pages 702-707 lecture notes.

Slides:



Advertisements
Similar presentations
Somatic Mutations in Cancer
Advertisements

Early Embryonic Development Maternal effect gene products set the stage by controlling the expression of the first embryonic genes. 1. Transcription factors.
Chapter 12 Genes and Cancer
Cancer: a genetic disease of inherited and somatic mutations n Gene mutations and/or genetic instability are involved in many cancers. n Viruses and environmental.
Lecture 4 Mosaic analysis Maternal/zygotic screens Non-complementation screen Cytogenomics to genomics Designer deletions Gene disruption in Drosophila.
A few thoughts on cancer and cancer family syndromes Pamela McGrann, MD. Department of Medical Genetics.
Describe the structure of a nucleosome, the basic unit of DNA packaging in eukaryotic cells.
Retinoblastoma by Michele Chasteen What is Retinoblastoma? n n Tumor of the eye that can occur at a high frequency in children and sporadically at an.
Analysis of gene function Loss-of-function  Many gene knock-out have no obvious phenotypes  Redundancy?  No perfect redundancy => subtle phenotype Gain-of-function.
Tumor Suppressor Genes
Microbial Genetics (Micr340) Lecture 6 Genetic Analysis.
Chromosomes, Chromatids, Mitosis!. Genomes, Chromosomes, DNA, Genes Eukaryotic genomes are made up of multiple chromosomes. Each chromosome contains one.
Copyright (c) by W. H. Freeman and Company Chapter 24 Cancer.
Tumor Markers Epidemiology 243: Molecular Epidemiology.
BRCA Genes Dallas Henson.
What is Cancer? How it occurs and cell cycle regulation.
Chromosomes, Mapping, and the Meiosis-Inheritance Connection
Chapter 23 – Cancer Genetics. Tumor Mass of abnormally dividing cells –Normal cells exhibit contact inhibition in culture Benign –Usually well-defined.
Angelina Jolie The White Coat Wonder. Rational  The purpose of our research is to enrich the Premed-A community with the knowledge of other cancers caused.
Mosaic Analysis Reading: ; & lecture notes Problem set 7.
The Cell Cycle & Cancer Mader Chapter 24.1.
The Cell Cycle. Overview What are the various stages of the cell cycle? What are the various stages of the cell cycle?
8.7 Mutations KEY CONCEPT Mutations are changes in DNA that may or may not affect phenotype.
Cancer &Oncogenes. Objectives Define the terms oncogene, proto-oncogenes and growth factors giving examples. Describe the mechanisms of activations of.
Tumor Suppressors Versus Oncogenes. The Cancer Phenotype is Usually Recessive R. Weinberg, Cancer Biology.
Mutations.
BRCA1: Tumor Suppression and Breast Cancer A breast cancer cell dividing.
Problem 1 James is the only person in his kindred affected by DMD. He has one unaffected brother, Joe. DNA analysis show that James has a deletion in the.
Genetics of Cancer Genetic Mutations that Lead to Uncontrolled Cell Growth.
Essentials of Biology Sylvia S. Mader
Molecular Cell Biology of the Yeast Saccharomyces cerevisiae Lecture I: Biology, Genetics, Genomics and Proteomics Zhang Yi, National Institute of Biological.
Genetics: Sex-Linked Inheritance
Announcements Exam I next Tuesday (2/17) Will cover all material through lecture this week.
CHAPTER 19 THE ORGANIZATION AND CONTROL OF EUKARYOTIC GENOMES Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings Section D: The.
Lecture 28 Genetics of Cancer Copyright © 2010 Pearson Education Inc.
Genetics NewsGenetics News Helen Fillmore talks today on therapies for neurodegenerative diseases. 12:30. Here. Problem Set 10 on line.
Javad Jamshidi Fasa University of Medical Sciences, December 2015 Cancer Genetics Session 4 Medical Genetics.
Genetics of Cancer Genetic Mutations that Lead to Uncontrolled Cell Growth.
Cancer Notes What is cancer? Cancer is a group of more than 100 diseases that develop over time and involve abnormal growth of certain cells.
Gene Interaction.
MOSAIC ANALYSIS.
Tumor Suppressors Versus Oncogenes. Retinoblastoma is a Cancerous Disease Hereditary childhood cancer: bilateral tumors in 25-30% of cases unilateral.
1 Recombination and Mapping (cont’d). 2 Interference Interference: this is a phenomenon in which the occurrence of one crossover in a region influences.
Cancer Chapter 4 Supplement. Cancer - important facts Cancer is uncontrolled cell growth It requires several steps to form It is very different depending.
Tumor Suppressor Gene Involved in Breast and Ovarian Cancers SCIENCE96/gene.cgi?BRCA1.
T.H. Morgan – 1910 –Working with fruit fly, Drosophila melanogaster –Discovered a mutant male fly with white eyes instead of red –Crossed the mutant male.
Mutagenesis and Genetic Screens. Genome-Wide Phenotypic Analysis: “Phenomics”
TSC1/Hamartin and Facial Angiofibromas Biology 169 Ann Hau.
1 The Big Picture: an outline of the concepts covered to date 1.Genes are physical units of hereditary that carry information from one generation to the.
Cancer. Cancer is a disease of the cell cycle Caused by one or more of the following: Increase in growth signals Loss of inhibitory signals In addition,
8.7 Mutations KEY CONCEPT Mutations - changes in DNA that may or may not affect phenotype.
The Problem of Cancer. What are cancer cells ? Cancerous growth involves unrestrained proliferation (malignancy) and spread (metastasis). Caused by: mutations.
Retinoblastoma Retinoblastoma is a rare form of eye cancer that develops in the retina usually before the age 5.
Reading for Monday’s lecture: ( genetic mosaics & chimeras ) p518 (“Aneuploid Mosaics…”) pp (“What cells…”) I will hold office hours during spring.
GENETICS A Conceptual Approach
GENETICS A Conceptual Approach
GENETIC BASIS OF CANCER
p53 function and regulation in normal cells and cancer cells
CANCER.
The Cell Cycle and Cancer
Clinical Genetics Lecture 4.
Chapter 17: Regulation of cell number
PTEN Tumor Suppressor and Cancer
Review session: Th Apr 5, 7-9 pm (location to be determined)
When: can mutations occur
Understanding Human Cancer in a Fly?
Genetic Damage and Mutation
Presentation transcript:

Mosaic screens Reading: pages lecture notes

white can be used as cell autonomous marker to monitor the loss of sev.

Mutant clone Analyze ommatidia at the periphery of mutant clone. These will be mosaic, containing both wild-type and mutant cells.

Approaches to identifying genes involved in development. 1.Direct screens: will often fail to identify essential genes required earlier in development (exception- hypomorphic mutations). 2.Sensitized screens: enhancer screens. 3.FLP/FRT mosaic screens.

Yeast 2 micron plasmid encodes a FLP recombinase and two FRT sites. FRT FLP FRT

X FLP recombinase stimulates recombination between two FRT sites.

Since replication origin fires only once during cell cycle. Intramolecular recombination is thought to increase copy number of 2 micron plasmid.

X P[w+] replication Mitotic crossing over P[w+] Expression of FLP recombinase can stimulate mitotic recombination at FRT sites. FRT

FLP recombinase expressed from the eyeless promoter results in recombination just in the developing eye.

A digression Mutations in two types of genes can lead to cancer 1. Oncogenes Positive regulators of the cell proliferation Activating mutations 2. Tumor suppressor genes Negative regulators of cell proliferation Loss-of-function mutations

Tumor suppressor genes Cell proliferation Tumor suppressor genes Cell death Tumor suppressor genes can either inhibit cell proliferation or promote cell death.

Retinoblastoma is cancer of cone cells that is inherited as an autosomal dominant trait. Sporadic Rb-cancer in one eye Inherited Rb-cancer in both eyes 3% inherited cases have deletion in 13q14 In 1971 Knudson proposed that in inherited forms of Rb a second mutation occurred spontaneously in the normal gene. In other words, while Rb is inherited as a dominant trait, it is recessive at the cellular level.

How would I identify a tumor suppressor gene in Drosophila?

eyFLP w y FRT P[w + ] w FRT m eyFLP w y FRT m w X eyFLP w y FRT P[w + ] w If m is in tumor suppressor gene, white cell will produce more cells than red cell How to identify a tumor suppressor gene in Drosophila?

To screen for tumor suppressor genes, mutagenize and look for mutants with excessive white tissue. w FRT w Balancer X w w w FRT or EMS Mutagenized chromosome males females F1

Cross individual F1 females w Balancerw FRT m X eyFLP w FRT P[w + ] eyFLP w FRT P[w + ] w FRT m F2 progeny w/o balancer Some chromosomes will have mutations in tumor suppressor genes. female males F1

eyFLP w FRT P[w + ] w FRT m eyFLP w FRT m w X eyFLP w FRT P[w + ] w If m is in tumor suppressor gene, white cell will produce more cells than red cell F2 progeny w/o balancer

Screen for mutations on each chromosome (FRT near centromere for each chromosome arm) Mutations define 23 genes Some were known tumor suppressor genes that had been identified in humans. Others were new genes, and their human homolgs were found to be mutated in cancer cells.