Biology Reference
In-Depth Information
largest study of its kind to date, a sequence comparison of orthologous and paral-
ogous members of the primate T-cell receptor
(
TCRB
; 7q35) gene family, micro-
deletion breakpoints appear to be frequently flanked by polypyrimidine runs and
sequences which possess marked homology to the deletion hotspot consensus
sequence (Funkhouser
et al
., 1997).
8.2.2 Microdeletions mediated by direct repeats
Micro-deletions occur during gene evolution at a frequency 10% that of
nucleotide substitutions (Saitou and Ueda, 1994). Pairwise comparisons of the
noncoding regions of human, rabbit and murine
-globin genes have shown that
they differ from each other in terms of numerous deletions/insertions and
Efstratiadis
et al
. (1980) proposed that the short direct repeat (2-8 bp) sequences
immediately flanking these sites could have templated the generation of these
lesions by slipped mispairing (
Figure 8.2
). Direct repeats may also have been
involved in generating the two inactivating single base-pair deletions (del C822
and del G904) noted in the human
-1,3 galactosyltransferase (
GGTA1
; 9q34)
gene (Larsen
et al
., 1990; see Chapter 6, section 6.2.2). Since chimpanzees possess
both these deletions, whereas orangutan and gorilla only have del904, it would
5' FLANKING
Human
Human
LARGE INTRON
Human
Human
Human
Human
Rabbit
Mouse
Rabbit
Mouse
Mouse
Mouse
Mouse
Mouse
3' NONCODING
Human
Human
Human
Human
Human
Human
Rabbit
Human
CCA-------GCATAAAA
CCAGGGCTGGGCATAAAA
A
A
Y
A
Y
G
Y
ATGACTTTT----ATTAGAT
ATGACTTTTCTTTATTAGAT
TGTGTGTGTGTGTG--------------------TGTGTGTGTGTG
TGTGTGTGTGTGTGTGTGTGTGCGCGCGTGTGTTTGTGTGTGTGTG
AAGTA-----------------CTTTCTCTAATC
AGTCCTTCTCTCTCTCCTCTCTCTTTCTCTAATC
TGGTAG--------------------------------AAACAACT
TTGGCTTTTATGCCAGGGTGACAGGGGAAGAATATATTTTACATAT
TGACATAGG--------------------------------------------ATTCT
TGTCATAGAATAATTCTTTTTTATTTTTTATTTATTATTTTTTTCATAGAATAATTCT
TGTGTGTGG------------AGTGTT
GGTGTGTGGATGTGAATTGTGAGTGTT
maj
min
maj
min
CAGGT-----------GTTCCT
CCAATTTCTATTAAAGGTTCCT
GCAATACAAA----------------------------------------------TAATAAAAT
GTCCAACTACTAAACTGGGGGATATTATGAAGGGCCTTGAGCATCTGGATTCTGCCTAATAAAAA
ATACAA--------------------------------------------TAATAAA
TATTTTCTGAACTTGGGAACAATGAATACTTCAAGGGTATGGCTTCTGCCTAATAAA
AAAAATTAT---------------------------------------GGGGACA
AATTTCTATTAAAGGTTAATTTGTTCCCTAAGTCCAACTACTAAACTGGGGGATA
β
A
γ
β
A
γ
Figure 8.2.
Examples of deletions flanked by short direct repeats within non-coding
sequences of mammalian
-globin genes (redrawn from Efstratiadis
et al
., 1980). Pairwise
alignments of sequences within non-coding regions of mammalian
-globin genes are
shown. A deletion is assumed in the upper sequence with respect to the lower sequence.
Dashes denote the nucleotides not present in the upper sequence. Short direct repeats are
underlined. The two aligned human A
large intron sequences are those of two different
alleles.
