Lecture 37 Prof Duncan Shaw. Textbooks in the library Emery's Elements of Medical Genetics by RF Mueller & ID Young, or PD Turnpenny for latest edition.

Lecture 37

Prof Duncan Shaw

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

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

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

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

Chromosome structure - packing ratio

• Packing ratio is the length of the DNA divided by the length into which it’s 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

2m long• Packing ratio = 14000/2 = 7000• So, there must be an efficient packaging

mechanism

Error correction in DNA replication

• Overall error rate is about 10-10 per division

• About 1 mistake per cell per division in humans

DNA mismatch repair

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

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