Download 20.1 Structural Genomics Determines the DNA Sequences of Entire

Benjamin A. Pierce
GENETICS
A Conceptual Approach
FOURTH EDITION
CHAPTER 20
Genomics and Proteomics
© 2012 W. H. Freeman and Company
Chapter 20 Outline
• 20.1 Structural Genomics Determines the DNA Sequences
of Entire Genomes, 558
• 20.2 Functional Genomics Determines the Functions of
Genes by Using Genomic-Based Approaches, 570
• 20.3 Comparative Genomics Studies How Genomes
Evolve, 575
• 20.4 Proteomics Analyzes the Complete Set of Proteins
Found in a Cell, 582
20.1 Structural Genomics Determines the
DNA Sequences of Entire Genomes
• Structural genomics- organization and sequence of
genetic information contained within a genome
• Genetic maps
– (linkage map) approximate locations of genes, relative to
the location of other genes, based on the rates of
recombination
– Limitations
• Low resolution or detail
• Do not correspond to physical distances between genes
20.1 Structural Genomics Determines the
DNA Sequences of Entire Genomes
Physical map: based on the direct analysis of
DNA, places genes in relation to distances
measured in bp, kbp, and mbp
20.1 Structural Genomics Determines the
DNA Sequences of Entire Genomes
• Sequencing the Entire Genome
• The Human Genome Project
20.1 Structural Genomics Determines the
DNA Sequences of Entire Genomes
• Whole-genome shotgun sequencing:
Small-insert clones are prepared directly from
genomic DNA and sequenced in a highly
automated way.
Concept Check 1
A contig is:
a. a set of molecular markers used in genetic
mapping
b. a set of overlapping fragments that form a
continuous stretch of DNA
c. a set of fragments generated by a restriction
enzyme
d. a small DNA fragment used in sequencing
Concept Check 1
A contig is:
a. a set of molecular markers used in genetic
mapping
b. a set of overlapping fragments that form a
continuous stretch of DNA
c. a set of fragments generated by a restriction
enzyme
d. a small DNA fragment used in sequencing
20.1 Structural Genomics Determines the
DNA Sequences of Entire Genomes
• Single-nucleotide polymorphisms:
• A site in the genome where individual
members of a species differ in a single base
pair
• Haplotype: the specific set of SNPs and other
genetic variants observed on a chromosome
• Linkage disequilibrium
• Tag SNPs
• Genome-wide association studies
20.1 Structural Genomics Determines the
DNA Sequences of Entire Genomes
• Copy-number variations (CNV)
• The number of copies of DNA sequences
varies from people to people.
• Expressed-Sequence Tags (ESTs)
• Markers associated with DNA sequences that
are expressed as RNA
• Bioinformatics:
• Molecular Biology + Computer Science
Concept Check 2
The ab initio approach finds genes by looking for:
a.
b.
c.
d.
common sequences found in most genes
similarity in sequences with known genes
mRNA with the use of in situ hybridization
mutant phenotypes
Concept Check 2
The ab initio approach finds genes by looking for:
a.
b.
c.
d.
common sequences found in most genes
similarity in sequences with known genes
mRNA with the use of in situ hybridization
mutant phenotypes
20.1 Structural Genomics Determines the
DNA Sequences of Entire Genomes
• Metagenomics- sequencing genomes of entire
communities of organisms
• Synthetic Biology-the creation from scratch
novel organisms
20.2 Functional Genomics Determines the
Functions of Genes by Using Genomic-Based
Approaches
• Functional genomics
• characterizes what the sequences do
• Transcriptome: all the RNA molecules
transcribed from a genome
• Proteome: all the proteins encoded by the
genome
20.2 Functional Genomics Determines the
Functions of Genes by Using Genomic-Based
Approaches
Predicting Function from Sequence
• Homologous
• Genes that are evolutionarily related
• Orthologs
• Homologous genes in different species that
evolved from the same gene in a common
ancestor
• Paralogs
• Homologous genes arising by duplication of a
single gene in the same organism
Concept Check 3
What is the difference between orthologs and
paralogs?
a. Orthologs are homologous sequences; paralogs
are analogous sequences.
b. Orthologs are more similar than paralogs.
c. Orthologs are in the same organism; paralogs are
in different organisms.
d. Orthologs are in different organisms; paralogs are
in the same organism.
Concept Check 3
What is the difference between orthologs and
paralogs?
a. Orthologs are homologous sequences; paralogs
are analogous sequences.
b. Orthologs are more similar than paralogs.
c. Orthologs are in the same organism; paralogs are
in different organisms.
d. Orthologs are in different organisms; paralogs are
in the same organism.
20.2 Functional Genomics Determines the
Functions of Genes by Using Genomic-Based
Approaches
• Gene Expression and Microarrays:
• Nucleic acid hybridization: using a known
DNA fragment as a probe to find a
complementary sequence
• Gene Expression and Reporter Sequences:
• Reporter sequence: encoding an easily
observed product used to track the
expression of a gene of interest
20.2 Functional Genomics Determines the Functions of
Genes by Using Genomic-Based Approaches
•Genomewide Mutagenesis
•mutagenesis screen
20.3 Comparative Genomics Studies How
Genomes Evolve
•Prokaryotic Genomes
•Genome size and number of genes
•Horizontal gene transfer
•exchanging genetic information from closely related
or distantly related species over evolutionary time
•Function of genes
20.3 Comparative Genomics Studies How
Genomes Evolve
•Eukaryotic Genomes
•Genome size and number of genes
•Segment duplications and multigene families
•Gene deserts
•Transposable elements
•Protein diversity
•Homologous genes
•Colinearity between related genomes
20.3 Comparative Genomics Studies How
Genomes Evolve
•Comparative Drosophila Genomics
•The Human Genome
20.4 Proteomics Analyzes the Complete
Set of Proteins Found in a Cell
• Determination of cellular proteins
• Two-dimensional polyacrylamide gel
electrophoresis (2D-PAGE)
• Mass spectrometry
20.4 Proteomics Analyzes the Complete
Set of Proteins Found in a Cell
• Affinity Capture
• interactome
• Protein Microarrays
• Structural Proteomics