Prof Duncan Shaw

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Lecture 37

• Prof Duncan Shaw

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Textbooks in the library

• Emery's Elements of Medical Genetics by RF
  Mueller ID Young, or PD Turnpenny for latest
  edition
• A general genetics textbook, such as Genetics
  (Principles and Analysis) by DL Hartl and EW
  Jones

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Introduction

• Previous lectures covered genes, proteins, cells
  etc. as isolated things
• Genes vary between individuals and between
  populations
• Genetic variation is crucial for differences
  between individuals
• In normal characteristics (e.g. height, weight,
  mental ability)
• In susceptibility to disease

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Cells divide, DNA replicates

• Cells must divide. Obvious, because 1 cell
  (fertilised embryo) becomes 3x1012 cells in human
  body
• DNA and genes must be accurately copied - errors
  would stop genes functioning
• The Cell cycle is crucial - this is where DNA is
  replicated - if it goes wrong, can cause trouble
  e.g. cancer

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Replication of DNA

• When not replicating, DNA in chromosomes is
  highly organised
• Replication starts at several sites in chromosome
  (origins of replication) where DNA starts to
  unwind
• Replication is catalysed by a complex of enzymes
  at the Replication Forks
• Continues outwards from origins until all DNA is
  replicated

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Chromosome structure - packing ratio

• Packing ratio is the length of the DNA divided by
  the length into which its packaged
• Smallest human chromosome (21) has 4x107 bp of
  DNA, 10 times size of E. coli genome
• Equivalent to 14mm of extended DNA
• In most condensed state the chromosome is about
  2mm long
• Packing ratio 14000/2 7000
• So, there must be an efficient packaging mechanism

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Error correction in DNA replication

• Overall error rate is about 10-10 per division
• About 1 mistake per cell per division in humans

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DNA mismatch repair

• When DNA gets damaged e.g. by chemicals, radiation

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The human genome

• Its size is 3 x 109 bp (3000Mb) for a single copy
• Contains 23 pairs of chromosomes
• About 35,000 genes
• Other mammals have about the same amount of DNA
  and number of genes, but often have different
  number of chromosomes