This document outlines the structure and content of a three-part lecture series on the human genome taking place from October 12-16, 2014. Part I will provide an introduction and overview of genome sequencing technologies. Part II will discuss the human genome project and sequencing methods. Part III will cover genome assembly, annotation, outcomes including the number of genes and functional categories, and applications such as SNP analysis and genome-wide association studies. The overall goals are to understand principles of genome analysis and the impacts of the human genome project.

1. The Human Genome
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Dr. Hasan Alhaddad
Guest lecturer: Molecular Basis of Human Diseases
October 12th, 14th, 16th 2014
Room 244 (1 PM)

2. Lectures structure
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• Part I (Sunday Oct 12th):
• The book of life (Matt Ridely’s analogy with
modifications).
• Introduction to the technologies at the time.
• Part II (Tuesday Oct 14th):
• Why sequencing genomes/the human genome?
• Genome war (public and private projects).
• Sequencing the genome.
• Part III (Thursday Oct 16th):
• Genome assembly revisited.
• Genome annotation.
• Genome outcome.
• The Genomic era.

3. AIMS (part III)
• Learn the basic principles and terminology of
genome assembly.
• Understand the importance of genome annotation.
• Become familiar with the outcomes of the human
genome.
• Understand the technologies and applications that
were developed due to the human genome project.
• Become familiar with the OMICS.
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4. Genome Assembly Revisited
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5. Genome Assembly Revisited
DNA sequence: The sequence reads that gets
produced by sequencing machine.
This can be considered the primary sequence of the
genome.
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6. Genome Assembly Revisited
Sequence alignment: order and connect overlapping
sequence reads to for a Contig.
This is something you are likely to do when you
sequence a gene.
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7. Genome Assembly Revisited
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We can consider Contigs the secondary level of
genome assembly.

8. Genome Assembly Revisited
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Scaffolds are the tertiary
level of genome assembly.
Scaffolds are also referred to
as Super Contigs.
Scaffolds are formed by
connecting ordered Contigs.

9. Genome Assembly Revisited
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Scaffolds are formed by connecting ordered and
Contigs. How?

10. Genome Assembly Revisited
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11. Genome Assembly Revisited
Genome assembly quality is measured by Contig/scaffold N50 or
similar measures.
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12. Genome Assembly Revisited
What affects the quality of genome assembly?
1.Repeat elements.
2.Variations between the individuals sequenced
(segmental duplications).
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13. Genome Annotation
Genome annotation is very important to study the biology of an
organism.
Without a proper annotation, the sequence is useless.
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Remember!
A book that cannot be read and understood is
useless knowledge

14. Genome Annotation
The genome sequence can be classified into different groups
based on the overall sequence composition and structure.
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Genome
Coding Non-coding
Genes
Proteins or RNA
Introns
Regulators
Etc.
Repetitive DNA
Interspersed Tandem
SINE
LINE
LTR
Transposons
Satellite
Minisatellite
Microsatellite

15. Genome Annotation
Genome annotation can be divided into two
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approaches:
1.Structural annotation:
1. Largely in silico.
2. Utilizing the accumulated knowledge of genes and
genomes to identify sequence signatures.
2.Functional annotation:
1. Requires a lot of work and time.
2. Studying the function of the book/code.
3. Involves biochemical analyses of the genome.
4. Gene expression and regulation.

16. Structural annotation
Start End
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Introns
Exons
5’ UTR 3’ UTR
Un-Translated Region
Promoter
sequence
Regulation
sequence

17. Structural annotation
Hidden Markov Models are used
for bioinformatic annotation
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18. Genome Outcome
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19. Genome Outcome
A time line of the developments in genomics
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20. Genome Outcome
Number of genes in the human genome ~ 22K and
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constitute ~1.5% of the genome

21. Genome Outcome
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Genes categorized

22. Genome Outcome
Genes
categorized
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23. Genome Outcome
Disease genes
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24. Genome Outcome
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Potential Drug targets

25. Genome Outcome
RNA gene are present in multiple copies in the
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human genome. WHY?

26. Genome Outcome
Exon and intron size compared to other taxa
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27. Genome Outcome
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Overall GC content of the human genome

28. Genome Outcome
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GC is correlated with genes

29. Genome Outcome
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GC is correlated with genes
CpG islands in the promoter region can regulate
gene expression

30. Genome Outcome
We are repeat elements with some genes :-)
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31. Tandem Repeat elements
Microsatellite: Short Tandem Repeats (STR) – Simple Sequence
Repeats (SSR)
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Minisatellite: Variable Number Tandem Repeats (VNTR)
Repeat unit size = hundreds base pairs
Repeated 4 times
Repeat unit size = 2 - 6 base pairs
Repeated 8 times Repeated 20 times

32. Tandem Repeat elements
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33. Genome Outcome
• Evolutionary relationship.
• Syntenic region are the
conserved regions across
taxa.
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34. Genome Outcome
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A summary of each chromosome

35. Genome Outcome
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36. SNP as a marker
Single Nucleotide Polymorphism
1. Many are found in through out
the genome.
2. Found in nuclear and
mitochondrial DNA.
3. No need for a lot of DNA.
4. Can be used on degraded DNA.
5. Easy to detect – many
platforms.
6. Polymorphism lower than
microsatellites.
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37. SNP as a marker
The SNPs identified by the human genome project
allowed the development of SNP arrays (SNP chip).
SNP array allows surveying the genome for variations
between individuals easily at a low price.
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38. SNP as a marker
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39. SNP as a marker
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Commercial uses of SNP markers to
learn about ancestry and health

40. SNP as a marker
Genome-wide
Association studies
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(GWAS)

41. Beyond the genome
The ENCycleopedia Of
DNA Elements
1. Transcripts
2. Regulatory elements
3. Enhancers
4. Silencers
5. Origins of replication
6. CpG islands
7. Histone modification sites
8. Open chromatin sites
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42. Beyond the genome
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Genome papers are no longer news

43. The OME Era
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44. The OME Era
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