GeneGenome Structure

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Gene/Genome Structure

• September 16, 2003

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Gene Structure and the Human Genome
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Things You Have to Hear About Today
Get

• Definition of a Gene
• Description of a Generic Eukaryotic Gene
• Packaging of the Genome
• Chromosomes
• Chromosome Structure
• Specialized Regions of Chromosomes
• Composition of the Human Genome

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What are Genes?

• Historically Defined as a Unit of Inheritance
• In 1866 Gregor Mendel described the Gene Theory
• Work Rediscovered in 1900
• Concept Existed Long Before the Chemical Nature
  of DNA was Understood

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What are Genes?

• The functional and physical unit of heredity
  passed from parent to offspring
• Genes are pieces of DNA, and most genes contain
  the information for making a specific protein

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Gene This is Your Life
DNA
Transcription
Processing
mRNA
AAA
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Organization of a GENE
Intron
Promoter
3-Untranslated Region (3-UTR)
5-Untranslated Region (5-UTR)
Exons
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Reading the Gene of the Gene
Processing
mRNA
AAA
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Things You Have to Hear About Today

• Definition of a Gene
• Description of a Generic Eukaryotic Gene
• Packaging of the Genome
• Chromosomes
• Chromosome Structure
• Specialized Regions of Chromosomes
• Makeup of the Human Genome

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Cell
Histones
DNA
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2 nm
11 nm
RESULT

• Each DNA molecule is packaged into a chromosome
  50,000X shorter than its extended length

30 nm
300 nm
700 nm
1400 nm
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Packaging of DNA
30 nm
Nucleosomes
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Packaging of DNA
Interphase
Mitosis
1 µm
10 µm
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Chromosome Banding/Karyotyping
Banding pattern is due to differential
staining of different regions of a given
chromosome
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Things You Have to Hear About Today

• Definition of a Gene
• Description of a Generic Gene
• Packaging of the Genome
• Chromosomes
• Chromosome Structure
• Specialized Regions of Chromosomes
• Makeup of the Human Genome

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Specialized Regions of Chromosomes

• Origins of replication
• Eukaryotic chromosomes have many origins
• Centromere (1 per)
• Attaches chromosome to the mitotic spindle
  apparatus
• Telomere (2 per)
• Linear end of the chromosome

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Function of Centromeres

• Centromeres are at the center of the chromosome
• Allow a single copy of each chromosome to be
  pulled into each cell when a cell divides
• Protein complex termed a kinetocore attaches the
  chromosomes to the mitotic spindle

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Telomeres

• Serves as caps for the linear end of the
  chromosome
• Prevents DNA from being degraded
• Prevents recombination
• Made up of repeating sequences
• The End Replication Problem

3
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Origins of Replication
Centromeres
Telomeres
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Things You Have to Hear About Today

• Definition of a Gene
• Description of a Generic Gene
• Packaging of the Genome
• Chromosomes
• Chromosome Structure
• Specialized Regions of Chromosomes
• Makeup of the Human Genome

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Genome Comparison
Organism
Size
Genes
Gene Density
Human 3000 million 30-35 K
1/100,000
Mouse 3000 million 30,000
1/100,000
Fruit Fly 135 million 13,061
1/13,781
Arabidopsis 100 million 25,000
1/4,000
C. elegans 97 million 19,099
1/5,079
Yeast 12.1 million 6,034
1/2,005
Bacteria (E. coli) 4.67 million 3,237
1/1,443
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Human Genome

• 3.2 x 109 base pairs of DNA
• 30,000-35,000 genes
• Arranged in 23 pairs of chromosomes
• 22 pairs of autosomal chromosomes
• 1 pair of somatic (either XX or XY)
• Only 1-2 of the genome encodes proteins

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Human Genome Contains a High Percentage of
Non-Coding DNA

• Introns
• Telomeres
• Highly repetitive DNA sequences
• Satellite DNA (repeats of up to 1,000,000 bp)
• Moderately repetitive DNA sequences
• Alu sequences

All these sequences may contribute to genetic
diversity
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Rate of Sequencing of the Human Genome
200
150
Millions of Base Pairs
100
50
1996
1997
1998
Completed by 2003
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What have we learned??

• 30,000-35,000 genes in the genome
• 99.9 of DNA is the same in all people
• Function for 50 of the genes identified
• Chromosome 1 has the MOST genes (2968)
• Y Chromosome the fewest (231)

Future Challenges Abound
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Future Considerations

• Functional Analysis/Interpretation
• Identification of Disease Genes
• Disease Diagnosis
• Other Inherited Traits
• Ethical Considerations

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Things You Have to Hear About Today

• Definition of a Gene
• Description of a Generic Gene
• Packaging of the Genome
• Chromosomes
• Chromosome Structure
• Specialized Regions of Chromosomes
• Makeup of the Human Genome