Introduction to Human

Behavioral Genetics

Huntington Disease (HD):

Discovered in 1872

Unit 1:
Introduction and Overview

Huntington Disease
(Module F - Supplementary)

Huntington Disease (HD): An autosomal dominant

disorder that illustrates
Population differences in
frequency (prevalence)
Non-Mendelian inheritance
Molecular diagnostics

HD: A neurological degenerative disorder

Problem
Domain

Early-Stage
HD

Mid-Stage
HD

Late-Stage
HD

Involuntary

Balance

Incontinent

Clumsiness

Walking

Vegetative

Organizing

Memory Loss

Speech loss

Movement

Cognitive
Flexibility

Learning

Depression

Delusions

Psychological

Dementia
Vegetative

Irritability

Insomnia

http://www.tumblr.com/search/huntington%27s+disease

YouTube video of a young man with HD

Frequency (prevalence) of HD
varies throughout the world

http://www.youtube.com/watch?v=JzAPh2v-SCQ

Reprinted by permission from Macmillan Publishers Ltd: Warby, S. C., et al. (2011). HTT
haplotypes contribute to differences in Huntington disease prevalence between Europe
and East Asia. European Journal of Human Genetics, 19(5), 561-566.

Huntington Disease has a variable age of

onset

Age of onset in Huntington Disease

Variable (neonate to late-life)
On average, earlier if mutation transmitted by father than by mother
On average, earlier in offspring than in parent generation

Conneally, P. M. (1984). Huntington Disease: Genetics and epidemiology.

American Journal of Human Genetics, 36(3), 506-526.

Anticipation (in genetics)

When an inherited disorder has an age of onset (severity) that, on
average, occurs earlier across successive generations

In the gene that is mutated in HD,

the bases CAG are repeated in
tandem a variable number of times
1 ttg
ggg
61 gca
tgc
121 cgc
gga
181 cgg
tgc
241 att
cgg
301 ggg
aag
361 tcc
cag
421 cag
ccg

ctg
gcg
gag
tgg
ggc
cgc
gtc
ttt
gcc
ccc
cgg
ctg
ttc
cag
cag
ccg

tgt
ggc
tcc
ccg
ccc
aag
caa
tac
ccg
gag
gag
atg
cag
cag
cag
ccg

gag
tgg
gca
gcg
gcc
gcg
gat
ctg
gtg
gcc
acc
aag
cag
cag
cag
ccg

gca
ttc
ggc
tgg
tcc
ccg
gga
cgg
ctg
tcc
gcc
gcc
cag
cag
cag
cct

gaa
cct
tag
ccc
gcc
tgg
cgg
ccc
agc
ggg
atg
ttc
cag
cag
ccg
cct

cct
ggc
ggc
cgc
ggc
ggg
ccg
aga
ggc
gac
gcg
gag
cag
cag
cca
cag

gcg
cag
tgt
ctc
gca
ctg
ctc
gcc
gcc
tgc
acc
tcc
cag
cag
ccg
ctt

ggg
cca
caa
cgc
cgt
ccg
agg
cca
gcg
cgt
ctg
ctc
cag
cag
ccg
cct

gca
ttg
tca
cgg
ctg
gga
ttc
ttc
agt
gcc
gaa
aag
cag
cag
ccg
cag

23 CAG repeats in a normal/usual Huntington disease gene

The variable number of CAG account

for the anomalies seen with HD

HD: The first genetic disorder with

molecular premorbid (predictive) testing

HD is due to a large # of CAG repeats (36 or more)

Questions clinicians had

The larger the # of repeats the earlier the onset

The # of repeats can increase across generations

How many would say they want to get the test?

How many would actually get the test?
Why do at-risk individuals get the test?
What are the risks associated with getting a positive result?

The increase in repeats is greater if transmitted by a

male than by a female

How a young woman faces these questions:

http://www.nytimes.com/2007/03/18/health/18huntingt
on.html?_r=1&ref=science&oref=slogin