gek1532 genetics of vision

8/6/2019 GEK1532 Genetics of Vision

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GEK1532

Genetics of Color Vision Defects

Thorsten Wohland

Dep. Of Chemistry

S8-03-06

Tel.: 6516 1248

E-mail: [email protected]

Color Vision, Perspectives from different disciplines, Eds. W. Backhaus, R.Kliegel, S. Werner, QP483 Col (SL): Chapter 5

Pictures of DNA etc. are adapted from Biochemistry, Voet & Voet, John Wiley


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Neurons

http://www.drugabuse.gov/

MOM/TG/momtg-introbg.html

Soma: the cell body; its task is theproduction of neurotransmitters and

the summation of the signal. As

well some input.

Dendrites: The dendrites are the

points of input of the neuron.

Axon: The axon is responsible for

the output of the neuron.

Synapse: Connection between two

neurons from an axon (presynaptic)

to a dendrite or cell body

(postsybaptic).

Network of neurons: Neurons can

have many inputs on the dendrites

or cell body from other neurons.

And through the axon they can

communicate to many other

neurons.


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Summation of signals

http://zeus.rutgers.edu/~ikovacs/SandP/c_fig2.jpg

The upper synapse is excitatory,the lower synapse inhibitory.

Their signal strength is indicated

by the black arrows.


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The Axon: Voltage gated cation

channelsResting potential of the membrane is -70 mV. Na+ ions are more abundantoutside the cell, and K+ ions are more abundant inside the cell. A difference in

concentartion between the two creates the resting potential

1. At a synapse channels open and

depolarize the membrane due to a

neurotransmitter.

2. Because of the depolarization,

voltage-gated cation channels open and

let Na+ ions into the cell, further

depolarizing the cell.

3. This opens more voltage-gated cation

channels and the impulse can travelalong the membrane.

4. After a short opening the voltage-

gated cation channels close

automatically and stay inactive for a few

milliseconds.

http://www.accessexcellence.org/AB/GG/action_Potent.html


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The overall picture of an synaptic

event

http://web.mit.edu/rujira/www/4.206/neuron/synapse.html


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Remember the rhodposin

activation?

Control of Cation channel. Since rhodopsin activation leads to the synthesis of

GMP from cGMP, the cGMP concentration decreases.

When the cGMP concentration decreases cation channels close. Themembrane will be hyperpolarized.


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Signal from light sensitive cells


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Cone opsin differences

Red-Pigment Blue-Pigment

Differences to Green-Pigment are indicated in dark shading.

From Scientific American, Special on Color (German Version)


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Deoxyribonucleic acid (DNA)

DNA is the code which gives a cell the

information how to construct proteins

Proteins are made of 20 different aminoacids

Thus DNA has in some way to encode for

these 20 different possibilities

Lets start with a look at what DNA actually

is!


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Bases:

Sugars:


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Double stranded DNA, Watson-

Crick base pairs


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But how does the DNA code for the

20 amino acids that are found in

proteins?

It is a 4 letter code: A, C, G and T

Thus the code must be at least 3 bases long:

1. A, C, G, T 2. A, C, G, T 3. A, C, G, T

4 x 4 = 16

4 x 4 x 4 = 64


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How could we get out of three

bases 20 amino acids?

Some of the 20 amino acids areencoded by more than just one codon.

This solves as well the problem of a

21st

code that signals a stop in theDNA code.


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http://cellbio.utmb.edu/cellbio/nucleus2.htm

TOO LONG!


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Genetic inheritanceHumans have 23 pairs of chromosomes:

1 pair of sex chromosomes

22 pairs of autosomes (non-sex chromosomes)

http://www.windows.ucar.edu/tour/link=/earth/Life/genetics_intro.html

To get an idea how DNA is actually wrapped up into chromosome, see:http://cellbio.utmb.edu/cellbio/nucleus2.htm

Cell cycle: http://www.biology.arizona.edu/cell_bio/tutorials/cell_cycle/cells3.html


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Inheritance

Offspring get for all chromosome pairs 1

chromosome form the father and one from

the mother

However, female offspring have 2 x

chromosomes, male have one x and one y

chromosome

Thus male offspring always inherit only

one x chromosome, that from the mother


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Inheritance

Am1,Am2 Af1,Af2

Am2,Af1 Am2,Af2Am1,Af1 Am1,Af2

Dominant inheritance: If a gene on one autosome is defect, the anomaly will be

present.

Recessive inheritance: Only if the particular gene on both autosomes is defective

will the anomaly manifested itself.


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Color deficencies

Xm1,Xm2Xf,Yf

Protanopia, Deuteranopia:

Only if both X chromosomes

are defective then will the

female be color deficient.

If one X chromosome is normalit can rescue the female.

Protanopia, Deuteranopia:

If the X chromosomes is

defective then the male will be

color deficient.

The genes for the middle and long wavelength opsin are located on the X chromosome

Tritanopia: The gene for the short wavelength opsin

is located on autosome 7

Dominant Inheritance (incomplete): defect of one

chromosome is enough to confer tritanopia.


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Example

XpXn XnY

XnY XpYX

p

YXnXnXnXp XnXn

XpXn XpXp XpXn XpXnXnY XpY XnY


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The genes for the middle and long wavelength opsin are located on the X

chromosome

The gene for the short wavelength opsin is located on autosome 7

Backhaus Fig. 5.3


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L and M opsins

1 2 3 4 5 6

DNA

Intron Exon

DNA containing only

the exons, the code

for the actual protein

2 3 4 5Since Exon 1 and 6 are the

same for M and L opsins, we

regard only exons 2 to 5

On the X chromosome we need at least 1 L and one M opsin for normal color

vision

Most commonly there are 3 opsins

It is more usual to have multiple M opsins

L M M


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Amino acid changes leading to

spectral shifts

Exon 5: Y277F and T285A -> 16-24 nm shift in peak sensitivity

Exon 3: S180A -> 4-7 nm shift

Backhaus Fig. 5.3


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spectral shifts

M pigment peaks around 530 nm

L pigment peaks around 550 nm

Backhaus Fig. 5.4


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spectral shifts

M pigment peaks around 530 nm

L pigment peaks around 550 nm

Backhaus Fig. 5.5

Mutations in L opsin are usually more pronounced than in M opsin.


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Backhaus Fig. 5.6 and 5.7


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Crossover of X chromosomes can

produce color deficiency gene

arrays

Backhaus Fig. 5.8

Deutan and color normal men

Protan men and femal carriers

normal

Deuteranopia


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Backhaus Fig. 5.9

Exon 5: Y277F and T285A -> determines whether opsin is L or M

Exon 3: S180A -> is more common in L

Occurrence of LS180 and LA180 is almost equal (50% each)

For MA180 93%, MS180 7%

Men have 50% chance to

have either LS180 or LA180

Women have 25% chance to have

LS180 LS180

LA180 LA180

LS180 LA180

LA180 LS180

50% chance to have

mixed L opsins


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An example of a womans retina

with mixed L pigments

Backhaus Fig. 5.10


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Summary

DNA

Inheritance of color deficiency

Spectral Tuning of L and M opsins

gek1532 genetics of vision

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