Transcript Document

Evolutionary dissection of ARMD event on LIPH gene
Jin-Han
1
Bae ,
1Division
Sang-Je
1
Park ,
Jae-Won
2
Huh ,
Dae-Soo
3
Kim ,
and Heui-Soo
1
Kim
of Biological Sciences, College of Natural Sciences, Pusan National University, Busan 609-735, Republic of Korea
2National
Primate Research Center (NPRC), KRIBB, Ochang, Chungbuk 363-883, Republic of Korea
3Korean
BioInformation Center, KRIBB, Daejeon 305-806, Republic of Korea
http:// www.primate.or.kr
Abstract
Results & Discussion
LIPH gene (Lipase member H) located on human 3q27 is
reported to be related to hair growth and loss by deletion
mechanism of fourth exon. The deletion mechanism is
occurred by the homologous recombination and excision
event of similar Alu elements of AluSc and AluY. In this
report, we investigated the evolutionary mechanism and
conservation of exon 4 sequences of LIPH gene. PCR
amplification indicated that AluY element have been
integrated into our common ancestor genome after the
divergence of Old World monkeys and Hominoid
primate. Sequencing analysis of various primates DNA
samples (5 hominoids, 6 Old World monkeys, and 4 New
World monkeys) of exon 4 region shows one nonsynonymous substitution, indicating that the region is
important portion for the functional protein. The
substitution event from Iso to Thr has been occurred in
hominoid lineage.………………………………...…………
L I P H (lipase, member H)
Chr.3
Exon
1
2 3
4
5
6
7
8
9
1
0
S
…
3q27
A
S
AluS
AluY
MIR
CDS
UTR
c
Insertion of AluY
M
HU
CH
Sequence analysis of Exon4 in LIPH
GO
G
I
JM
RM
641 b p
Sequence analysis of AluY
Introduction
Retroelement
Pseudogene
1%
Coding sequence
3% DNA element
3%
HERV element
8%
Gene-related
Sequence
36%
RNA intermediate
- LTR element
+ LTR element
Retroposon
- env
Amino acids of Exon4 in LIPH
+ env
Phylogenic analysis of Exon4 in LIPH
HU
Retrotrnasposon
- RT
GO
+ RT
LTR
SINE
ORF1
ORF2
I
BO
LTR
GI
Yeast Ty1/copia/truncated HERVs
OR
LINE
20%
LTR
P
Poly(A)
LTR
RH
Human THE1
JM
Human Alu
Other region
SINE
13%
16%
CE
Retrovirus
NM
LINE
P
ORF1
ORF2
L1
7SL-derived left
monomer
A-rich
connector
7SL-derived right
monomer
TSD
Poly(A)
LTR
gag
pol
env
LTR
II
MAN
LAN
Full-length HERVs/exogenous retrovirus
COL
poly(A)
TSD
A box
B box
Sequence analysis of Exon4 in various species
Materials & Methods
Gene Cloning
&
Sequencing
PCR
Bioinformatic
s
Hu
Ch
Canis
Mus
Gallus
Rabbit
Frog
Hu
Ch
Canis
Mus
Gallus
Rabbit
Frog
Hu
Ch
Canis
Mus
Gallus
Rabbit
Frog
Hu
Ch
Canis
Mus
Gallus
Rabbit
Frog
Template DNA
Hu
Ch
Canis
Mus
Gallus
Rabbit
Frog
94℃
Denature
50℃
Anneal
Primer
DNA polymerase
Extension
72℃
X 35
References
1. Kazantseva A, Goltsov A, Zinchenko R, Grigorenko AP, Abrukova AV, Moliaka YK,
Kirillov AG, Guo Z, Lyle S, Ginter EK, Rogaev EI. Human hair growth deficiency is
linked to a genetic defect in the phospholipase gene LIPH. Science. 2006 Nov
10;314(5801):982-5.
2. Ali G, Chishti MS, Raza SI, John P, Ahmad W. A mutation in the lipase H (LIPH) gene
underlie autosomal recessive hypotrichosis. Hum Genet. 2007 May;121(3-4):319-25.
Epub 2007 Feb 27.
3. Mills RE, Bennett EA, Iskow RC, Devine SE. Which transposable elements are active in
the human genome? Trends Genet. 2007 Apr;23(4):183-91. Epub 2007 Feb 27. Review.
http:// www.primate.or.kr