Human Molecular Genetics

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Human Molecular Genetics

• Dr. Yu-Wai Peter Lin
• Barry University
• School of Natural and Health Sciences

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DNA Structure and Function

• DNA, RNA and polypeptides are large polymers
  defined by a linear sequence of simple repeating
  units

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Structure of bases, nucleosides and nucleotides
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Structure of the Amino Acids

• Basic amino acids Positive charge
• Acidic amino acids Negative charge
• Polar amino acids Hydrophilic
• Nonpolar amino acids Hydrophobic

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DNA Structure and Replication

• The structure of DNA is an antiparallel double
  helix

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Antiparallel Helix

• Phosphodiester bonding and antiparallel nature of
  the two DNA strands

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Double Helix

• Base complementarity
• Watson-Crick rules
• A -- T
• G -- C

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Intramolecular Hydrogen Bonding in DNA and RNA
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DNA Replication is Semi-conservative
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Asymmetry of Strand Synthesis during DNA
replication
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The Chromosomes of Complex Organisms have
multiple replication origins
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RNA Transcription and Gene Expression

• The flow of genetic information is almost
  exclusively one way
• DNA to RNA to Protein

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RNA is transcribed as a single strand which is
complementary in base sequence to one strand
(template strand) of a gene
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Template Strand Antisense
Strand Nontemplate Strand Sense
Strand
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Eukaryotic Promoters

• Eukaryotic promoters consist of a collection of
  conserved short sequence elements located at
  relatively constant distances from the
  transcription start site

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Tissue-specific Gene Expression

• Tissue-specific gene expression involves
  selective activation of specific genes and
  regions of transcriptioanlly active chromatin
  adopt an open conformation

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Unmethylated CpG Islands

• Unmethylated CpG islands frequently mark the
  position of actively transcribing genes in
  vertebrate genomes

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RNA Splicing

• RNA splicing ensures removal of intronic RNA
  sequence from the primary transcript and fusion
  of exonic RNA sequences

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RNA Splicing Consensus sequences

• Consensus sequences at the splice donor, splice
  acceptor and branch sites in introns of complex
  eukaryotes

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Mechanism of RNA splicing

• Small nuclear ribonucleoprotein particles
  (snRNPs) are directly involved in the splicing
  reaction

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Translation, Post-translational Processing and
Protein Structure

• Translation is the process whereby mRNA is
  decoded on ribosomes to specify the synthesis of
  polypeptides

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Expression of the Human Beta-Globin Gene

• 5 3 untranslated sequences
• 5 3 UTS
• Phase 0 intron
• Phase 2 intron

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The Genetic Code is Deciphered by Codon-Anticodon
Recognition

• AUG Translation start point
• 5 to 3 direction
• tRNA anticodon
• mRNA codon
• Stop codon

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Polypeptides are synthesized by Peptide bond
formation between successive Amino Acid
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The Nuclear and Mitochondrial Genetic Codes are
Similar but not Identical

• Degeneracy of the code most often involves the
  third base of the codon

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Insulin Synthesis

• Insulin synthesis involves multiple
  post-translational cleavages of polypeptide
  precursors

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Structure of an Alpha-Helix

• Regions of secondary structure in polypeptides
  are often dominated by intrachain hydrogen bonding

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Structure of a Beta-Pleated Sheet

• Hydrogen bonding occurs between the CO oxygen
  and NH hydrogen atoms of peptide bonds on
  adjacent parallel segments of the polypeptide
  backbone

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Disulfide Bridges

• Intrachain and Interchain disulfide bridges in
  human insulin

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Major DNA Repair Pathways

• Base excision repair
• DNA glycosylase
• AP endonuclease
• DNA Polymerase
• DNA Ligase

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Nucleotide Excision Repair

• Thymidine dimer
• Nuclease cleavage
• Helicase

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