Biology Reference
In-Depth Information
To date, some 250 human zinc finger genes have been allocated a symbol and
some have been chromosomally localized. Inspection of the available mapping
data reveals at least 9 distinct clusters of zinc finger genes in the human genome:
3p21-p22 (
ZNF52
,
ZNF64
,
ZNF35
,
ZNF166
,
ZNF167
,
ZNF168
), 6p21 (
ZNF76
,
ZNF165
,
ZNF173
,
ZNF204
), 8q24 (
ZNF7
,
ZNF16
,
ZNF34
), 10p11 (
ZNF11A
,
ZNF25
,
ZNF33A
,
ZNF37A
), 10q11 (
ZNF11B
,
ZNF22
,
ZNF33B
,
ZNF37B
),
11q23 (
ZNF123
,
ZNF125
,
ZNF128
,
ZNF129
,
ZNF145
), 19p12-p13 (
ZNF43
,
ZNF56
,
ZNF58
,
ZNF66
,
ZNF67
,
ZNF85
,
ZNF90
,
ZNF91
,
ZNF92
,
ZNF208
),
19q13 (
ZNF42
,
ZNF45
,
ZNF83
,
ZNF93
,
ZNF132
,
ZNF134
,
ZNF135
,
ZNF136
,
ZNF137
,
ZNF146
,
ZNF154
,
ZNF155
,
ZNF160
,
ZNF175
), 22q11 (
ZNF69
,
ZNF70
,
ZNF71
,
ZNF74
). This superfamily has presumably evolved through
cycles of gene transposition and duplication. Duplications in the ZNF91 family
are known to have occurred some 55 Myrs ago in the common ancestor of the
simians (Bellefroid
et al
., 1995).
The human
ZNF45
and
ZNF93
genes are very similar to their murine ortho-
logues although the human genes encode more zinc finger repeats than their
murine counterparts, consistent with the occurrence of intragenic deletions/
duplications (Shannon and Stubbs, 1998). Similarly, the human transcription fac-
tor MOK2 (
MOK2
; 19q13.2-q13.3) contains 10 zinc finger motifs in comparison
to 7 in the murine homologue (Ernoult-Lange
et al
., 1995).
Olfactory receptor genes.
The olfactory system is thought to be capable of dis-
tinguishing several thousand odorant molecules. This is potentiated by olfactory
receptors (ORs) which are responsible for the recognition and G protein-medi-
ated transduction of specific odorant signals. With possibly 1000 members in the
human genome, the OR gene superfamily constitutes by far the largest family
encoding G protein-coupled receptors. OR genes are intronless and occur in clus-
ters that are present at more than 25 chromosomal locations in the human
genome. However, more than 70% of human OR-homologous sequences are prob-
ably pseudogenes (Rouquier
et al.
, 1998; Trask
et al.
, 1998).
Human OR gene clusters appear to be disproportionately located in subtelom-
eric regions and have been subject to frequent duplications and inter-chromoso-
mal rearrangements (Trask
et al
., 1998) some of which appear to have been
mediated by recombination between repetitive sequence elements (Glusman
et al
.,
1996). OR genes within the clusters belong to at least four different subfamilies
which display as much sequence variability within clusters as between clusters
(Ben-Arie
et al
., 1993). The classification of human OR genes is still in its infancy
but chromosomally localized members include
OR1A1
, 17p13;
OR1D2
,
OR1D4
,
OR1D5
, 17p13;
OR1E1
,
OR1E2
, 17p13;
OR1F1
, 16p13;
OR1G1
, 17p13;
OR2D2
,
11p15;
OR3A1
,
OR3A2
,
OR3A3
, 17p13;
OR5D3
,
OR5D4
, 11q12;
OR5F1
, 11q12;
OR6A1
, 11p15;
OR10A1
, 11p15.
The olfactory system is combinatorial in that one OR can recognize multiple
odorant molecules, and one odorant molecule may be recognized by multiple
ORs, whilst different odorants are recognized by different combinations of ORs
(Malnic
et al
., 1999). Each nasal olfactory sensory neuron expresses only one allele
of a single OR gene (Chess
et al
., 1994; Sullivan
et al
., 1996). In the olfactory
epithelium, different sets of ORs are expressed in distinct spatial zones; neurons