1. Genomics
Chapter 18

2. Mapping Genomes Genetic maps Physical maps
Abstract maps that place the relative location of genes on chromosomes based on recombination frequency
Physical maps
Use landmarks within DNA sequences, ranging from restriction sites to the actual DNA sequence

3. First genetic maps were linkage maps
Distances reflected recombination frequencies between genes
Measured in centimorgans (cM)
Limitations
Distances between genes determined by recombination frequencies do not directly correspond to physical distance on a chromosome
Conformation of DNA can affect frequency of recombination
Not all genes have obvious phenotypes to look for in crosses

4. Whole Genome Sequencing
The ultimate physical map is the base-pair sequence of the entire genome
Automation of this process increased the rate of sequence generation
Genome sequencing is one case in which technology drove the science, rather than the other way around

5. To reduce errors, 5–10 copies of a genome are sequenced and compared
Sequencers provide accurate sequences for DNA segments up to 800 bp long
To reduce errors, 5–10 copies of a genome are sequenced and compared
Vectors used to clone large pieces of DNA
Yeast artificial chromosomes (YACs)
Bacterial artificial chromosomes (BACs)
Human artificial chromosomes (HACs)

6. The Human Genome Project
Originated in 1990 by the International Human Genome Sequencing Consortium
Goal of this publicly funded effort was to use a clone-by-clone approach to sequence the human genome
Craig Venter formed a private company and entered the “race” in May, 1998
Using shotgun-sequencing
In 2001, both groups published a draft sequence
Gaps in sequence still being filled
Still being revised

7. The Human Genome Project
In 2004, the “finished” sequence was published as the reference sequence (REF-SEQ) in databases
-3.2 gigabasepairs
-1 Gb = 1 billion basepairs
-Contains a 400-fold reduction in gaps
-99% of euchromatic sequence
-Error rate = 1 per 100,000 bases

8. Characterizing Genomes
The Human Genome Project found fewer genes than expected
-Initial estimate was 100,000 genes
-Number now appears to be about 25,000!
In general, eukaryotic genomes are larger and have more genes than those of prokaryotes
-However, the complexity of an organism is not necessarily related to its gene number

9. Genome Organization Genomes consist of two main regions -Coding DNA
-Contains genes than encode proteins
-Noncoding DNA
-Regions that do not encode proteins

10. Coding DNA in Eukaryotes
Four different classes are found:
-Single-copy genes: Includes most genes
-Segmental duplications: Blocks of genes copied from one chromosome to another
-Multigene families: Groups of related but distinctly different genes
-Tandem clusters: Identical copies of genes occurring together in clusters
-Also include rRNA genes

11. Noncoding DNA in Eukaryotes
Each cell in our bodies has about 6 feet of DNA stuffed into it
-However, less than one inch is devoted to genes!
Six major types of noncoding human DNA have been described

12. Noncoding DNA in Eukaryotes
Noncoding DNA within genes
-Protein-encoding exons are embedded within much larger noncoding introns
Structural DNA
-Called constitutive heterochromatin
-Localized to centromeres and telomeres
Simple sequence repeats (SSRs)
-One- to six-nucleotide sequences repeated thousands of times

13. Noncoding DNA in Eukaryotes
Segmental duplications
-Consist of 10,000 to 300,000 bp that have duplicated and moved
Pseudogenes
-Inactive genes

14. Noncoding DNA in Eukaryotes
Transposable elements (transposons)
-Mobile genetic elements
-Four types:
-Long interspersed elements (LINEs)
-Short interspersed elements (SINEs)
-Long terminal repeats (LTRs)
-Dead transposons

15. Variation in the Human Genome
Single-nucleotide polymorphisms (SNPs) are sites where individuals differ by only one nucleotide
-Must be found in at least 1% of population
Haplotypes are regions of the chromosome that are not exchanged by recombination
-Tendency for genes not to be randomized is called linkage disequilibrium
-Can be used to map genes

19. Genomics Organellar genomes
-Mitochondria and chloroplasts are descendants of ancient endosymbiotic bacterial cells
-Over time, their genomes exchanged genes with the nuclear genome
-Both organelles contain polypeptides encoded by the nucleus

20. Genomics
Transgenics is the creation of organisms containing genes from other species (transgenic organisms)
-Can be used to determine whether:
-A gene identified by an annotation program is really functional in vivo
-Homologous genes from different species have the same function

21. Applications of Genomics
Genomics has also helped in agriculture
-Improvement in the yield and nutritional quality of rice
-Doubling of world grain production in last 50 years, with only a 1% cropland increase

22. Applications of Genomics
Genome science is also a source of ethical challenges and dilemmas
-Gene patents
-Should the sequence/use of genes be freely available or can it be patented?
-Privacy concerns
-Could one be discriminated against because their SNP profile indicates susceptibility to a disease?