Biology Reference
In-Depth Information
FIGURE 5.10. Ideogram of chromosome 8 show-
ing regions of rearrangement in the family
(described by Haan et al. 1989) that were instru-
mental in identifying the BOR (Branchio-Oto-
Renal syndrome) locus. This family had both
BOR syndrome and Tricho-Rhino-Phalangeal
syndrome type 1 (TRPS1). A portion of 8q from
q13.3 to q21.1 was inserted in band q24.1, appar-
ently causing disruption of both the BOR gene
(
EYA1
) and the TRPS1 locus.
eight different mutations were found, including frameshifts and splice-site
variants, confirming that deletion of
EYA1
in the family with the dir
ins(8)(q24.1;q13.3q21.1) was pathogenetic for the BOR phenotype
(Abdelhak et al. 1997).
3. Expressed Sequence Tags
Another technique for identifying disease genes is the analysis of expressed
sequence tags (ESTs). The human genome is estimated to contain 50,000
to 100,000 genes, only a fraction of which have been identified. Over 90%
of human disease genes identified by positional cloning experiments have
exact sequence matches to one or more ESTs in GenBank, demonstrating
that sequence tags are useful identifiers of medically important genes. The
current collection of human ESTs has been estimated to represent over
60,000 distinct human genes; thus, much progress has been made in the
effort to identify all human genes.
ESTs are short stretches of cDNA sequence, usually less than 500 base
pairs (Adams et al. 1991). Because the sequence is derived from cDNA, the
gene represented was transcribed in the tissue from which the original
mRNA was isolated. ESTs provide a sequence handle to identify and clone
the complete gene, and give insight into which genes are expressed in
various tissues or cell types. Adams et al. (1991) originally described 600
ESTs from a human brain cDNA library; today there are over 4,500,000
ESTs in GenBank (http://www.ncbi.nlm.nih.gov/dbEST/), derived from
more than 100 different cDNA libraries.
