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 3x10 12 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 its packaged Smallest human chromosome (21) has 4x10 7 bp of DNA, 10 times size of E. coli genome Equivalent to 14mm of extended DNA In most condensed state the chromosome is about 2 m long Packing ratio = 14000/2 = 7000 So, there must be an efficient packaging mechanism

Error correction in DNA replication Overall error rate is about 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 10 9 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