Biology Reference
In-Depth Information
1
Structure and function in
the human genome
1.1 Introduction
Nothing in biology makes sense except in the light of evolution.
Theodosius Dobzhansky (1973)
The haploid human genome comprises 23 chromosomes containing between
them some 3.2 × 10
9
bp of DNA. The bulk of the genome comprises DNA
sequence of varying degrees of repetitivity whilst about 10% represents unique
(single copy) sequence containing perhaps 70 000 genes. The repetitive portion
contains a mixture of DNA sequence elements which may have a structural or
regulatory role or may be merely 'junk DNA' without obvious function
(Zuckerkandl, 1997). Human genes contain within them all the genetic informa-
tion necessary to specify the encoded proteins but they also contain further infor-
mation, in the form of a large number of different DNA sequence motifs that
serve to control mRNA expression, splicing, transport, and stability. This chapter
constitutes a short introduction to the structure, function and expression of the
human genome together with a brief description of the types of mutational lesion
in human genes that have been found to be responsible for inherited disease.
1.1.1 Chromosome structure and function
DNA plays a role in life rather like that played by the telephone directory in
the social life of London: you can't do anything much without it, but, having
it, you need a lot of other things - telephones, wires, and so on - as well.
C.H. Waddington (1968)
Chromatin structure.
Human chromosomes contain DNA in a highly coiled
and condensed form, organized and packaged by structures known as
nucleo-
somes
. Chains of nucleosomes comprise a '10 nm fibre' and this is coiled to form
the '30 nm fibre' which is in turn further coiled to form
chromatin
(reviewed by
Kornberg and Lorch, 1992; Paranjape
et al
., 1994; Wolffe, 1992). The highest
degree of condensation is found in transcriptionally inactive regions, those
regions in which mRNA synthesis from specific genes is turned off. To allow
transcriptional activation of a gene (i.e. to allow the enzyme RNA polymerase to
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