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Molecular Genetics

• Genetic information
• Location
• Interpretation
• Translation
• Transmission of genetic information
• Variations in genetic information

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Genetic information

• Chromosomes are found almost exclusively in
  nucleus
• Except red blood cells, all human cells have a
  nucleus
• DNA (deoxyribonucleic acid)
• carrier of the genetic information
• two strands (double helix)

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Figure 12.2 Eukaryotic chomosomes
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Figure 12.3 Chromosome duplication and
distribution during mitosis
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Nitrogenous base, Nucleoside, and Deoxynucleoside
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Nucleoside and Nucleotide
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DNA Base Pairing

• Watson and Crick a complementary pairing, via
  hydrogen bonding, of guanosine (G) with cytidine
  (C) and adenosine (A) with thymidine (T).

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Double Helix Structure
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More about DNA

• Any two DNA fragments differ only w.r.t. the
  order of their linear sequence of bases
• the genetic information
• The primary structure of the DNA
• DNA length
• Basic unit is one nucleotide or one basepair (bp)
• The human DNA contains about 3.3 billion bp
• Nucleoside base distribution in DNA

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RNA (Ribonucleic Acid)

• Much shorter than DNA
• One strand
• Bases A, C, G, U (uracil)

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DNA and RNA
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Human Chromosomes

• 23 chromosomes
• 22 autosomes (122 long -gtshort, but 21 is
  the shortest)
• 1 sex chromosomes X or Y
• Haploid 221
• Diploid a double set

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Human Chromosomes
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human karyotype
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Human Chromosomes

• Two arms p (petit) and q (queue)

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Protein

• Most functions are carried out by proteins
• Consist of polypeptides a linear sequence of
  amino acids
• three bases (a codon) code for one amino acid
• 4364 codons, but 20 amino acids

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RNA Codons for Protein Synthesis
The third position often redundant
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Central Dogma
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Transcription and Translation

• A flash to explain the processes

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Meiosis

• how genetic information can be transmittedf from
  generation to teneration
• a succession of events (two cell divisions)
• Prophase
• Metaphase
• Anaphase
• Telophase
• the number of possible combination in one gamete
  from one parent is 223

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Mitosis and Meiosis

• An excellent animated comparison of Mitosis and
  Meiosis
• Flash provided by NOVA online
• Homologous versus sister chromatids
• Recombination

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Variations in Genetic Info

• Locus versus Allele
• at each locus an individual possesses two alleles
• Genotype versus Phenotype
• Homozygous versus Heterozygous

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Variation in the DNA sequence

• Two main sources
• During cell division
• Insertions, deletions, inversions,
  translocations, duplications

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Alterations of chromosome structure
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(also non-reciprocal translocation)
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Variation in the DNA sequence

• Two main sources
• During cell division
• Insertions, deletions, inversions,
  translocations, duplications
• During DNA replication
• Mutation / Polymorphism
• Transitions (within purines and pyrimidines)
• Transversions (between purines and pyrimidines)
• Synonymous versus Nonsynonymous
• Frameshift mutation

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Silent mutation Mis-sense Non-sense
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Frameshift Mis-sense Frameshift Non-sense No
frameshift
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Detection of Variations in the DNA sequence

• PCR (polymerase chain reaction)
• Amplification of DNA
• Each PCR cycle contains
• Denaturation high T
• Hybridization low T
• Elongation med T
• Sequencing
• Primers Probes
• Fluorescent dyes

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High-throughput platforms

• working in single or low-plex mode
• SEQUENOM
• Matrix-assisted laser desorption ionisation
  time-of-flight (MALDI-TOF) mass spectrometry
• Pyro-sequencing
• Applied Biosystems' TaqMan technology
• multiplexed version of the oligoligation assay
  (OLA)
• Applied Biosystem's SNPlex technology
  simultaneously detect 48 SNPs

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Ultra High-throughput platforms

• Array-based SNP typing
• custom-designed arrays of smaller size
  (1500-20,000 SNPs)
• GoldenGate assay from Illumina
• MegAllele assay from ParAllele/Affymetrix.
• 100K 500K SNPs in a single experiment
• GeneChip microarrays from Affymetrix
• BeadChip arrays from Illumina

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HOMEWORK1

• Group projects
• Transcription
• Translation
• Mitosis and Meiosis