Download Human genome

Systems Biology – the global study of multiple components
of biological systems and their interactions
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New approach to studying biological
systems has made possible
Sequencing genomes
 High-throughput platform development
 Development of powerful computational tools
 The use of model organisms
 Comparative genomics
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Changes in biology, genetics and genomics from
human genome sequence
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Genetics parts list
Speeds gene-finding and gene-function analysis
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Sequence identification in second organism through
homology
Gene function in one organism helps understand
function in another for orthologous and paralogous
genes
Genes often encode one or more protein domains
Ready access to identification of known human
polymorphism
Speeds mapping of new organisms by comparison
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e.g., mouse and human have high similarity in gene content and
order
How transcription factor protein domains have
expanded in specific lineages
Fig.
10.14
Conserved
segments of
syntenic blocks
in human and
mouse genomes
Fig. 10.15
Major insights from human and
model organism sequences
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Approximately 40,000 human genes
Genes encode noncoding RNA or proteins
Repeat sequences are > 50% of genome
Distinct types of gene organization
Combinatorial strategies amplify genetic information and
increase diversity
Evolution by lateral transfer of genes from one organism to
another
Males have twofold higher mutation rate than females
Human races have very few unique distinguishing genes
All living organisms evolve from a common ancestor
Questions Remain about the
Human Genome
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Difficult to precisely estimate number of genes
at this time
Full genome not accurately sequenced
 Small genes are hard to identify
 Some genes are rarely expressed and do not have
normal codon usage patterns – thus hard to detect
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Protein coding genes generate the
proteome
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Proteome – collective translation of 30,000 protein
coding genes into proteins
Complexity of proteome increase from yeast to
humans
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More genes
Shuffling, increase, or decrease of functional modules
More paralogs
Alternative RNA splicing – humans exhibit significantly
more
Chemical modification of proteins is higher in humans
Examples of domain accretions in chromatin proteins
Fig. 10.16
Number of distinct domain architectures in
four eukaryotic genomes
Fig. 10.17
Repeat sequences fall into five classes
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Transposon-derived repeats
Processed pseudogenes
SSRs
Segmental duplications of 10-300 kb
Blocks of repeated sequences at centromere,
telomeres and other chromosomal features
Gene organization of genome
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Gene families
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Gene-rich regions
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Closely related genes clustered or dispersed
Functional or chance events?
Gene deserts
Span 144 Mb or 3% of genome
 Contain regions difficult to identify?
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e.g., big genes – nuclear transcript spans 500 kb or
more with very large introns (exons < 1% of DNA)
Class II region of human major
histocampatibility complex contains
60 genes in 700 kb
Fig. 10.20
Lateral transfer of genes
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> 200 human genes may arise by transfer
from organisms such as bacteria
Lateral transfer is direct transfer of genes
from one species into the germ line of
another
Twofold higher mutation rate in
males
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Comparison of X and Y chromosomes
Same may be true for autosomes, but
difficult to measure
Majority of human mutation arise in males
Males give rise to more defects, but also
more diversity
Human Genome Project has changed the
potential for predictive/preventive medicine
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Provided access to DNA polymorphisms underlying human
variability
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Makes possible identification of genes predisposing to disease
Understanding of defective genes in context of biological systems
Circumvent limitations of defective genes
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Novel drugs
Environmental controls
Approaches such as stem-cell transplants or gene therapy
Social, ethical, and legal issues
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Privacy of genetic information
Limitations on genetic testing
Patenting of DNA sequences
Society’s view of older people
Training of physicians
Human genetic engineering
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Somatic gene therapy – inserting replacement genes
Germ-line therapy – modifications of human germ line