Biology Reference
In-Depth Information
appear that del904 was the original inactivating mutation (Galili and Swanson,
1991). C822 is immediately flanked by imperfect direct repeats (TACAGGC
C
T
and TACAAGGCAG, where
C
is nucleotide 822) that could have templated the 1
bp deletion via slipped mispairing. Slipped mispairing may also have been respon-
sible for the G904 deletion since G904 is the 3
most base of a string of five Gs.
A direct repeat may also have templated the single base deletion in the 5
flank-
ing region of the human interferon
10 (
IFNA10
; 9p22) gene relative to the other
-interferon genes (see
Figure 4.27
). Flanking direct AGGT repeats appear to have
mediated an AGG deletion exhibited by both orthologous and paralogous mem-
bers of the primate T-cell receptor
(
TCRB
; 7q35) gene family whilst in the same
gene family, overlapping 7 bp direct repeats (CTTTTCTTTTCT) may have
served to template a TTTCT deletion (Funkhouser
et al
., 1997).
8.2.3 Microdeletions mediated by inverted repeats
Inverted repeats may also have mediated the generation of microdeletions during
gene evolution. One example is the inactivating 13 bp deletion in exon 2 of the
gibbon urate oxidase gene (Wu
et al
., 1992; see Chapter 6, section 6.2.1); two
imperfect inverted repeats (CAAGAAC and GTTCATG) span the breakpoints of
this deletion. A 20 bp deletion has been reported from the 5
-glo-
bin (
Hbd
) gene of the colobus monkey,
Colobus polykomos
(Vincent and Wilson,
1989). This deletion, which spans the transcriptional initiation site used in Old
World monkeys and anthropoid apes, is responsible for a five-fold reduction in
Hbd
gene transcription as assessed by
in vitro
transcription assay. Inspection of the
putative deleted bases and the flanking DNA sequence reveals the presence of a 13
bp imperfect inverted repeat which could have been responsible for the deletion
through formation of a hairpin loop (
Figure 8.3
).
An inverted repeat also appears to have templated the deletion of a GAT codon
in the human interferon
region of the
-interferon
genes (
Figure 4.27
). Finally, a contiguous inverted repeat sequence (ATTC-
CCAGTTTCTGGGAAT) may well have templated an 8 bp deletion exhibited by
both orthologous and paralogous members of the primate T-cell receptor
2 (
IFNA2
; 9p22) gene relative to the other
(
TCRB
; 7q35) gene family (Funkhouser
et al
., 1997).
+1
C
aagggagggcagag--------------------CTTCTGA
R
g a a ccaactgttgcttATACTTG
B
g g a tcaactgttgcttACATTTG
S
c g g ctaactgttgcttTGACTTG
H
c g a tcgactgttgcttACACTTT
Figure 8.3.
Alignment of
-globin (
Hbd
) gene sequences from colobus monkey (C),
rhesus macaque (R), baboon (B), spider monkey (S) and human (H) showing the location
of a 20 bp deletion in the colobus monkey (after Vincent and Wilson, 1989). Transcribed
sequences are denoted by upper case letters, flanking regions are in lower case letters. +1
denotes the site of trancriptional initiation. Underlined bases represent an imperfect
inverted repeat which may contribute to the formation of a hairpin loop.
