Biology Reference
In-Depth Information
that outnumber their functional counterparts by some 15-30 fold (Lindgren
et al
.,
1985). This contrasts with the situation found for the U2 snRNA genes, where the
active genes outnumber the pseudogenes.
4.2.3 Gene superfamilies
The superfamily is used to describe a group of gene families whose individual
members share a common evolutionary origin, possess common features within a
family but differ with respect to certain other features between families. A selec-
tion of some of the most important human gene superfamilies will be presented.
Cadherin genes.
The cadherins are membrane-associated glycoproteins which
act as calcium-dependent cell adhesion molecules but which may also be involved
in signal transduction. Cadherins may be classified into four groups (classical,
desmosomal, protocadherins, cadherin-related proteins) which are structurally
similar, each containing an extracellular domain consisting of between 4 and 30+
repeats of an 110 amino acid cadherin-specific motif. Although classical cad-
herins appear to be confined to the vertebrates, the superfamily has ancient ori-
gins with members present in organisms as diverse as nematodes and humans.
The classical and desmosomal cadherins are thought to have evolved more
recently by a process of duplication and divergence from the primordial proto-
cadherin-like proteins (Suzuki, 1996).
A cluster of human classical cadherin genes is present at chromosome 16q22.1
(
CDH1
,
CDH5
,
CDH3
) with
CDH13
and
CDH15
located at 16q24 and
CDH11
not yet regionally localized on chromosome 16. Other genes encoding classical
cadherins are present on 5p13-p14 (
CDH12
) and 18q11 (
CDH2
) whilst a proto-
cadherin (
PCDH7
) gene has been mapped to 4p15.
Cytochrome P450 genes.
The cytochrome P450 enzymes comprise a large liver-
expressed family of heme-containing electron transport molecules which are
involved in the oxidative metabolism of a wide range of substrates including
steroids, drugs and xenobiotics. This family can be subdivided into sub-families
on the basis of structural and functional criteria and many are extremely poly-
morphic, for example CYP2D6 (Marez
et al
., 1997). With nearly 40 CYP P450
genes identified (and perhaps between 20 and 150 yet to be identified), this super-
family is one of the larger superfamilies represented in the human genome:
CYP1A1
and
CYP1A2
(15q22),
CYP1B1
(2p21),
CYP2A6
,
CYP2A7
,
CYP2A13
(19q13.1),
CYP2B6
and
CYP2B7
(19q13.2),
CYP2C8
,
CYP2C9
,
CYP2C10
,
CYP2C18
,
CYP2C19
(10q24),
CYP2D6
(22q13.1),
CYP2E
(10q24-qter),
CYP2F1
(19q13.2),
CYP2J2
(1p31),
CYP3A4
(7q22.1),
CYP4A11
(1),
CYP4B1
(1p12-p34),
CYP7A1
(8q11-q12),
CYP11A
(15q23-q24),
CYP11B1
and
CYP11B2
(8q21),
CYP17
(10q24.3),
CYP19
(15q21),
CYP21
(6p21.3),
CYP24
(20q13),
CYP26A1
(10q23-q24),
CYP27A1
(2q33-qter),
CYP27B1
(12q13.3-q14) and
CYP51
(7q21). Several gene clusters are apparent, for example on 10q24 and
19q13, and this is likely to reflect a history of gene duplication and divergence
(Hoffman
et al.
, 1995; Nelson
et al.
, 1996). A common origin may however also be
reflected by the possession of a similar exon/intron arrangement as in the case of
