Biology Reference
In-Depth Information
Chapter 6
Genetic Networks
Michael Costanzo
1
,
Anastasia Baryshnikova
1
,
2
,
Benjamin VanderSluis
3
,
Brenda Andrews
1
,
2
,
Chad L. Myers
3
and Charles Boone
1
,
2
1
Banting and Best Department of Medical Research, The Donnelly Center for Cellular and Biomolecular Research, University of Toronto,
Toronto, Ontario M5S 3E1, Canada,
2
Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 3E1, Canada,
3
Department of Computer Science and Engineering, University of Minnesota, Minneapolis, MN 55455, USA
Chapter Outline
Introduction
115
Genetic and Physical Interaction Networks
127
Defining Genetic Interactions
117
Genetic and Metabolic Networks
127
Negative Genetic Interactions
117
Mapping Genetic Interactions in Other Organisms
128
Positive Genetic Interactions
117
Genetic Interactions in Unicellular Organisms
128
Experimental Approaches to Map Genetic Interaction
Networks in Yeast
Genetic Interactions in Metazoan Model Systems
128
118
Genetic Interactions in Mammalian Model Systems
128
The Yeast Non-Essential Gene Deletion Collection
118
Genetic Interactions and Cancer Therapeutics
129
Genetic Interaction Mapping Technologies
118
Genetic Network Conservation
129
Quantifying Genetic Interactions
121
Conservation of Individual Interactions between
Orthologous Gene Pairs 129
Conservation of Genetic Network Structure and Topology 129
Expanding Genetic Networks: Mutant Alleles, Conditions
and Phenotypes 130
Conditional Alleles and Essential Genetic Interactions 130
Gain-of-Function Alleles 130
Condition-Specific Genetic Interactions 130
Quantitative Phenotypes to Measure Genetic Interactions 131
Genetic Interactions and Genome-Wide Association Studies 131
Acknowledgements
Quantitative Genetic Interaction Profiles Reveal the
Functional Organization of a Cell
121
Exploring Genetic Interaction Networks
122
Modular Network Structures Identify Functional
Relationships between Pathways and Complexes
122
Genetic Networks Enable Functional Dissection of
Pleiotropic Genes
125
Genetic Interactions as a Means of Studying the Evolution
of Gene Duplicates
125
Integrating Genetic Interactions with Other Biological
Networks
133
127
References
133
INTRODUCTION
The relation between an organism's genotype and its
phenotype may be governed by an underlying set of
complex genetic interactions
[1]
. To define the general
principles of genetic networks, we have mapped genetic
interactions systematically in the budding yeast Saccharo-
myces cerevisiae
[2
perturbations
[7]
. Genome-scale screens for genetic inter-
actions provide a means of exploring this buffering
capacity and mapping a functional wiring diagram of a cell.
In particular, synthetic genetic array (SGA) methodology
enables the systematic mapping of rare synthetic lethal
genetic interactions amongst the set of ~5000 viable dele-
tion mutants through an automated form of genetic analysis
that produces high-density arrays of double mutants
[4]
.In
addition to their functional information, the resultant
genetic networks may provide fundamental insights into
the genetic architecture underlying the genotype
4]
. Like most eukaryotic organisms,
the majority (~80%) of the ~6000 yeast genes are indi-
vidually dispensable, with only a relatively small subset
(~20%) required for viability
[5,6]
. The finding that most
genes are non-essential may be indicative of the evolution
of extensive buffering against genetic and environmental
e
pheno-
e
type relationship governing genetic diseases.
