Jin FanKevin Guise

Tobias SommerKarin Brocki

Michael Posner

http://development-of-attention.net

A

G

T

C

AGTCTCGATATCGATCCTCGCTCGACAGATCGA

AGTCTCGATATCGAACCTCGCTCGACAGATCGA

AGTCTCGATATCGAACGAACCTCGCTCGACAGATCGA

AGTCTCGATATCCTCGCTCGACAGATCGA

“snps”

“insertions, duplications”

“deletions”

STR Y-chr LOCUS #DYS393 14DYS19 14DYS391 10DYS439 10DYS389-1 12DYS389-2 17DYS388 12DYS390 22DYS426 11DYS385a 15DYS385b 16DYS392 11

HAPLOTYPE “G”Saudi Arabia, Iraq, Iran, Pakistan

The “real difficulty” in understanding genetic risk factors

Sizing up human height variation by Peter M Visscher

Genome-wide association studies have identified many variants affecting susceptibility to disease. Now, three studies use this approach to study adult height variation in a combined sample size of

approx 63,000 individuals and report a total of 54 validated variants influencing this trait.Nature Genetics 40, 489 - 490 (2008)

-80

-50

DRD2 activation suppressesCells in the resting state

DRD1 activation excitesCells in the -50 mV state

Coincident inputsWill drive a cell from -50 to -80 mV

ACTION POTENTIALS& SYNAPTICPLASTICITY

Can we deploy genetic markers as non-invasive proxies for mechanisms ?

word color

response

BLUE

NMDA

COMT DA

“gain”

+ *

+

+

+

+

D1= 400-1600 ms

400 ms

RT < 1700 ms

3500 - RT - D1 ms

100 ms

cue

target

Human Attention Network Task (ANT)

Distribution of normalized scores for executive attention

N = 200 normal adult volunteers

Stimulus-Response conflict score

0

10

20

30

40

50

60

70

80

90

0.05

0.15

0.25

0.35

This group“Slows down”duringincongruent trials

Correlation values between twin pairs of MZ and DZ twins for each network and mean RT._______________________________________Twin Alerting Orienting Conflict RT_______________________________________MZ .465* .099 .727** .740**

DZ .375 .395* .281 .659**

_______________________________________Note: * p < .05; ** p < .01

Heritability Alerting OrientingConflict RT_____________________________________________h2

F = 2 (rMZ – r DZ) .18 -.59 .89 .16h2

H = (rMZ – r DZ)/ .14 -.49 .62 .24 (1 – r DZ)ML fit:h2 .18 .00 .72 .16

ﾥAlerting networkﾥOrienting networkﾥExecutive control networkﾥAlerting networkﾥOrienting networkﾥExecutive control network

Fan et al., 2004

Dopamine Transporter

Dopamine Receptor

Monoamine Oxidase A

COMT

Low DA levels High DA levels

2030N =

VAR00002

2.001.00

Me

an +

- 1

SE

VA

R00

001

.24

.22

.20

.18

.16

.14

.12Co

nflic

t rat

io s

core

COMT Val 108/158MAOA long prom. repeat

COMT Met 108/158MAOA short prom. repeat

MAOA (4-repeat) – (3-repeat)

4-repeat, LOW MA

3-repeat, Hi MA

Rea

ctio

n T

ime

Dif

f

Red = activity biased by MAOA 4-repeat allele

Blue = activity biased by MAOA 3-repeat allele

Fan et al., 2003

Julie Williams and Michael C O’DonovanEuropean Journal of Human Genetics (2006) 14, 681–689

DYX1C1DCDC2

KIAA0319