9780521516358book.pdf

Estimates indicate that as little as 10% of the genome appears to encode enzymes and

proteins. Current estimates equate this to approximately 20000 genes which are import-

ant for human cellular development and maintenance. However it is the understanding

of the complete function of many of the genes and their variants coupled with their

interaction that now provides a major challenge. It also points to the fact that there is

an extensive use ofalternative splicingwhere exons are essentially mixed and matched

to form different mRNA and thus different proteins. The study further aims to understand

and possibly provide the eventual means of treating some of the 4000 genetic diseases in

addition to other diseases whose inheritance is multifactorial. In this respect there are a

number of specific genome projects such as the Cancer Genome Anatomy Project (CGAP)

which aims to understand the part certain mutations play in the development of tumours.

6.10 Pharmacogenomics

As a result of the developments in genomics new methods of providing targeted drug

treatment are beginning to be developed. This area is linked to the proposal that it is

possible to identify those people who react in a specific way to drug treatment by

identifying their genetic make-up. In particular SNPs may provide a key marker of

potential disease development and reaction to a particular treatment. A simple example

that has been known for some time is the reaction to a drug used to treat a particular

type of childhood leukaemia. Successful treatment of the majority of patients may be

achieved with 6-mercaptopurine. A number of patients do not respond well, but in some

cases it may be fatal to administer this drug. This is now known to be due to a mutation

Table 6.7Techniques used to determine putative gene-encoding sequences

Identification method Main details

Zoo blotting (cross-hybridisation) Evolutionary conservation of DNA sequences that
suggest functional significance

Homology searching Gene database searching to gene family-related
sequences

Identification of CpG islands Regions of hypomethylated CpG frequently found 5^0
to genes in vertebrate animals

Identification of open reading frames (ORF)
promoters/splice sites/RBS

DNA sequences scanned for consensus sequences

by computer

Northern blot hybridisation mRNA detection by binding to labelled gene probes

Exon trapping technique Artificial RNA splicing assay for exon identification

Expressed sequence tags (ESTs) cDNAs amplified by PCR that represent part of a gene

Notes:RBS, ribosome binding site; cDNA, complementary DNA.

259 6.10 Pharmacogenomics