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delta power density change after sleep deprivation compared to wild type,
which indicates that the depth of the rebound of NREM sleep is affected in
h
DEC2-P384R
animals. Consistent with the mammalian data, expressing
m
Dec2-P384R
in the sleep/rest center of
Drosophila
brain leads to signifi-
cantly less sleep-like behavior with decreased sleep bout duration and
increased sleep bout number versus flies expressing m
Dec2-WT
. In sum-
mary, these results demonstrate DEC2 as an important player in the regu-
lation of sleep homeostasis.
17. TIMELESS
Four SNPs in or near the
TIMELESS
gene are linked to depression with
fatigue in females, while two of these SNPs (rs7486220 A/G and
rs1082214 C/T) are also linked to depression with early morning awakening
in males. Notably, rs7486220 A and rs1082214 C correlate with depression
with fatigue in females, whereas rs7486220 G and rs1082214 T correlate
with depression with early morning awakening in males. In a separate set
of individuals that do not have depression, rs1082214 C is correlated with
higher levels of seasonal changes in mood in females, while rs1082214
T is correlated with early morning awakening and fatigue in males. Collec-
tively, these data implicate a connection between TIMELESS and gender-
dependent depression and sleep regulation.
18. CONCLUDING REMARKS
Studies of human clock-gene variants reveal that besides circadian
timing, clock genes may also be involved in a number of other biological
with sleep regulation, cancer development, metabolic traits, and mood dis-
orders, implying that these processes may have particularly close connections
with the circadian clock, and thus are more sensitive to alterations of the
clock caused by genetic variations. In addition,
CLOCK
,
PER1-3
, and
CK1e
polymorphisms are linked to addiction, suggesting a role for the clock
in reward circuitry of the brain.
BMAL1
and
NPAS2
polymorphisms are
related to fertility and seasonal variations, supporting the long-held view that
circadian clock participates in seasonal adaptability. Furthermore, studies
using mice deficient for clock genes verified the involvement of clock genes
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