Bioinformatics genetic projectx

fabulousgalaxyBiotechnology

Oct 1, 2013 (3 years and 10 months ago)

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Kathleen Eusebio

Bio 439

4/24/09

OCA2

Once upon a time, there was a little girl who had a gene that made her look different from
the other girls in her class. The little girl often visited special doctors in the hospitals and went
through many tests
. She could not play outside on bright sunny days like the other children. Her
eyes were very sensitive to light and impaired her vision.
OCA2 was what the
special
doc
tors
calle
d the gene. The gene realized he

was the cause for the little girl’s distinct f
eatures
. So he
went through a path of discovery using tools of bioinformatics to determine the
genetic reasoning

of this girl’s appearance.


T
he first thing to figure out was
the gene’s basic information.
OCA2 knew that was his

name but had no idea what it

meant. By using NCBI, OCA2 discovered the basics.
He

is
a
genomic DNA that causes protein coding.
O
culocutaneous albinism II was his full name and he

is
located on chromosome 15 q11.2
-
q12. The gene’s length is 344,438 bps starting at 25,673,616
and ending

at 26,018,053.
A nucleotide reference sequence NG_009846 of the gene gives
evidence that there are 24 exons
.

OCA2 was also able to discover his

nearest neighbors
in which
he never met. Their names are
GHBRG3 and HERC2.


OCA2 always did his

job within its

designated
location but never knew what his

main
function was. The gene discovered that’s its

function was to encode a protein, the human
homolog of mouse p, that is believed to be an integral membrane protein that transports TYR.
OCA
2 gene always wondered why
TYR would never work together

with him

and the only thing
OCA2 knew
was
that TYR is a precursor for melanin.


But what does that mean?” said the
OCA2 gene. Well, the gene dove more into NCBI and used OMIM. He discovered th
at a
mu
tation of OCA2 gene has a high variable phenotype. It causes oculocutaneous albinism II
which results with none or less pigmented skin, hair, and eye color due to no melanin production.
“Melanin causes color in skin, hair, and eyes and the little girl has
no color so maybe she has no
melanin?..maybe” said OCA2.


Genecard helped OCA2 understand a little more about its backgro
und. The gene
discovered that he

has re
latives in other animals.

Table 1

Orthologs for OCA2 gene from 9 species (
see top 5
)


Organism

Gene

Locus

Description

Human

Similarit
y

NCBI accessions

dog

(Canis
familiaris)

OCA2
1


--

oculocutaneo
us albinism II

85.91
(n)

86.55
(a)

488683

XM_545800.2

XP_545800.2


chimpanzee

(Pan
troglodytes)

OCA2
1


--

oculocutaneo
us albinism II

99.05
(n)

98.81
(a)

453261

XM_001162129.1

XP_00116212
9.1


mouse

(Mus
musculus)

Oca2
1
,
4

7 (28.00
cM)
4

oculocutaneo
us albinism
II
1, 4

79.69
(n)
1

79.69
(a)
1

18431
1

NM_021879.2
1

NP_068679.1
1



BC119220
4

BC120549
4


(
see all 6
)

ch
icken

(Gallus
gallus)

OCA2
1


--

oculocutaneo
us albinism II
(pink
-
eye
dilution
homolog,
more

71.65
(n)

73.86
(a)

428009

XM_425579.2

XP_425579.2


zebrafish

(Danio
rerio)

oca2
1


--

oculocutaneo
us albinism II

66.18
(n)

67.9
(a)

567419

XM_690715.3

XP_695807.3


fruit fly

(Drosophila
melanogaste
hoe2
2

hoe1
1

25B4
2

tyrosine
transporter
2

hoepel1
1

40
(a)

(best of
3)
2

249663
1

NM_135032.1
1

NP_608876.1
1


r)

56.15
(n)
1

52.98
(a)
1

African
malaria
mosquito

(Anopheles
gambiae)

AgaP_AGAP00928
4
1


--

AGAP00928
4
-
PA

55.82
(n)

52.47
(a)

1280250

XM_320080.1

XP_320080.1


thale cress

(Arabidopsis
thaliana)

AT1G02260
1


--

transmembra
ne protein,
putative

40.39
(n)

28.6
(a)

839344

NM_100106.3

NP_171728.2


rice

(Oryza
sativa)

Os02g0822100
1


--

hypothetical
protein

45.19
(n)

29.1
(a)

4331184

NM_001055091.1

NP_0010485
56.1




Orthologs found in other species was an amazing thought to OCA2. It helped the gene
understand that the m
utation its causing are not prone to just humans. Dogs, chimpanzees, cats,
and other
s

can all have mutations in their OCA2 ortholog which can cause albinism.


However, this only stirred up more curiosity for OCA2. A questioned popped up asking
“if I have f
amily in other species and the same species, what makes us all different?”.

Table 2

AB

Genomic Data

Transcription Data

Allele Frequencies

SNP ID

Valid

Chr 15
pos

Sequence

Re
cs

A
A

Ch
g

Type

Mo
re

Re
cs

Allele

freq

Pop

Total

sample

Mo
re





--

--

--


--

--




--



rs230525
3
1
,
2

C,F,H

2593722
3(
-
)

TGGGC
C
/
G
GAGTC

1

P/
R

mis
1

e
se
3


17


EA NA
MN
CSAM
EU WA

2876



rs389320
1
1
,
2

C,F,H

2567189
8(+)

TAAAA
T
/
C
GTCCT

1

--

ng3
1


11


NA EU
EA WA

978



rs176509
60
1
,
2

C,F,H

2567303
7(+)

CTGAG
G
/
A
GCACC

1

--

ng3
1


7


NA EU
EA WA

562



rs129039
14
1
,
2

C,F,H

2567343
1(+)

ATAGC
A
/
G
TGCAC

1

--

ng3
1


4


EU EA
WA

420



rs180041
4
1
,
2

C,F,H

2587063
2(
-
)

ACAGC
A
/
G
TAGGA

1

H/
R

mis
1

ese
3


21


EA NA
MN
2676


CSAM
EU WA


rs180040
7
1
,
2

C,F

2590391
3(
-
)

CTCCC
G
/
A
GGGAC

1

Q/
R

mis
1


10


MN
CSAM
EA NA
EU WA

906



rs717526
6
1
,
2

F,H

2567407
9(+)

ATGGG
T
/
C
TGTGA

1

--

ut3
1

ese
3


4


EU EA
WA

418



rs180040
1
1
,
2

C,F

2593364
8(
-
)

GCATC
C
/
T
GGGCC

1

R/
W

mis
1


7


MN
CSAM
EA NA

660



rs339294
65
1
,
2

C,F

2593714
9(
-
)

GGCGG
C
/
T
GGCCA

1

R/
W

mis
1


6


MN
CSAM
EA NA

476



rs340106
19
1
,
2

C,F

2593355
4(
-
)

GACGG
C
/
T
CATCC

1

A/
V

mis
1


5


MN
CSAM

400



OCA2 accessed Table 2 from Genecard

which only shows 10 of its 1742 SNPs
. By using
dbSNP
, OCA2 looked up the first snp rs 2305253.
A

snp stands for single nucleotide
polymorphism and this helped answer OCA2’s question.

These polymorphisms are individual
variations in genomic sequences. Specifically for rs 2305253,
there are changes between th
e C/G
in the nucleotide sequence. By looking up a snp reference number on dbSNP, OCA2 discovered
the difference between itself and a relative in China. OCA2s Chinese relatives have a frequency
of 0.958 for C/C and 0.042 C/G.


OCA2 decided
to be more detai
led with his research about himself. He decided to break
up his genetic
makeup

into mRNA and proteins and see what he can find about each. First, he
ran his mRNA sequence into mfold which folded his mRNA into a structure.





“WOW! This is what my fold
ed

mRNA looks like?!?!?!” said OCA2. MFold folded his
mRNA sequence and gave him a structure of the lowest energy structure possible with a
calculation of
-
1148.70 kcal/mol.



The protein sequence OCA2 stumbled upon was put into SOSUI to predict
transmembran
e helices.

He found that there his protein sequence predicts 12 transmembrane
helices.

Table 3

No.

N terminal

transmembrane region

C terminal

type

length

1

209

QWLKVMGLFAFVVLCSILFSLYP

231

PRIMARY

23

2

359

SVETQVTIATAILAGVYALIIFE

381

PRIMARY

23

3

385

RTLAAMLGSLAALAALAVIGDRP

407

PRIMARY

23

4

417

DFETLALLFGMMILVAIFSETGF

439

PRIMARY

23

5

456

WAMIIMLCLIAAVLSAFLDNVTT

478

PRIMARY

23

6

534

MGLDFAGFTAHMFIGICLVLLVC

556

SECONDARY

23

7

652

DGILLAKCLTVLGFVIFMFFLNS

674

PRIMARY

23

8

681

LDLGWIAILGAIWLLILADIHDF

703

PRIMARY

23

9

712

WATLLFFAALFVLMEALAHLHLI

734

PRIMARY

23

10

741

TALLIKMVPEEQRLIAAIVLVVW

763

SECONDARY

23

11

802

MYALAFGACLGGNGTLIGASANV

824

SECONDARY

23

12

844

RLGFPMMVVSCTVGMCYLLVAHV

866

PRIMARY

23



Unfortunately, OCA2 could not find his own protein structure. However, as he
discovered earlier that he might
code for

the human homolog of mouse p, he decided to put a
search for structural results of mouse p.

He found 1Z65.



Figure 2



The structure
provided shows that it is only 1 polymer

which is likely to be a prion
-
like
protein droppel. Its molecular function is copper ion binding and its cellular component is the
membrane.


OCA2 successfully research his background to fully understand his purpos
e. The little
girl is different because of him. In normal circumstances, he would be able to carry TYR which
causes melanin production. But since he is mutated, TYR does not work with him and melanin is
not properly produced.