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PSYC 3102: Introduction to Behavioral Genetics
Thursday 9/27/01
PKU – Phenotype and Genotype
Pleiotropy – characteristics include dyskinesia, cognitive defects, hypopigmentation
Hypopigmentation: in skin cells, tyrosine is made into DOPA, which is converted to
melanin (Figure 5.1) – this pathway is reduced in PKU, causing hypopigmentation
Nervous system: DOPA is converted to dopamine, which is converted to norepinephrine
Reduced dopamine in the basal ganglia causes motor problems
Once a basic gene gets messed up, there is a whole host of pathways upstream and
downstream that get messed up
Further points about PKU:
1. PKU is a recessive disease – you need 2 bad copies of the gene to get the disease; 1 good
blueprint makes sufficient enzyme that you don’t get the disease
2. PKU exhibits the type of disorder called a metabolic block
Figure 5.1 shows a metabolic pathway
PKU disrupts this pathway
In Figure 5.1, tyrosinosis, goitrous cretinism, alkaptonuria, & albinism are all genetic
disease that block the pathway at different points
3. There are multiple (hundreds) alleles (spelling differences in the gene) that can cause PKU
Having 2 mutations in the gene will cause PKU
Most people with PKU have 2 different faulty alleles
4. Variable expressivity
frequency
PKU
low
normal
IQ
Much of the variability in IQ in PKU has to do with genetic background
PKU kids with intelligent parents have IQ closer to normal
PKU kids with not-so-intelligent parents have lower IQ
high
5. The deleterious characteristics of PKU are preventable
Reducing phenylalanine in the diet prevents the buildup of phenylalanine waste products
that cause deleterious effects
The diet for PKU is specially constructed
To prevent symptoms, the diet must be started early in life and rigorously adhered to until
late childhood/early adolescence
Pregnant women with PKU must go back on the diet during pregnancy
The role of psychologists in PKU is to motivate compliance to the diet
OUTCOME IS DEPENDENT ON COMPLIANCE
6. Because PKU is preventable, there is mandatory genetic screening for PKU at birth in all 50
states, and in most, if not all, industrialized countries (called the Guthrie Test)
Test blood for phenylalanine, and if positive, do further tests
Impetus behind the testing is that PKU is preventable
Issue of mandatory genetic testing: there is a recommendation against genetic testing at
birth for disorders that cannot be fixed; if something can be done, as in PKU, then
mandatory testing is recommended
Issue of prenatal screening for Mendelian disorders: done when there is increased risk
(based on family history, parental age) but it is not advocated by genetic counselors
Ex. firstborn has PKU, so parents are carriers
Use prenatal screening for following children so parents can determine whether or
not to carry the pregnancy to term
Prenatal screening is at the discretion of the parents and are only done if the
parents may decide not to carry the baby to term
CAH – Congenital Adrenal Hyperplasia
- problem in the synthesis of cortisol from cholesterol
- one can get CAH by getting a metabolic block in any one of the 5 steps in the synthesis of
cortisol from cholesterol (Figure 5.3)
- this is an example of genetic heterogeneity – you can get the same or very similar genetic
syndrome by defects in any of several genes
- CAH also exhibits a metabolic block
- you must have 2 bad copies of one of the 5 genes to get CAH (can have 1 bad copy of one
gene, and 1 bad copy of another gene and will not get the disease)
- one of the really early ways that masculinization of a fetus takes place is by production of
androgens in an offshoot of this pathway (Figure 5.3)
if the pathway is blocked at the beginning, androgens are low and sex of males is
ambiguous
if the pathway is blocked towards the end, androgens are high (because the pathway is
backed up and excess androgens are made), and females are masculinized (externally –
internal sex organs are unaffected)
- androgens don’t just affect sex organs, and CAH alters brain development
Sheri Berenbaum - children with CAH are studied to look at the effects of too much/too
little hormone, normal brothers/sisters of CAH kids are used as controls
There are gender-related differences in toy preferences that are exhibited as soon as the
child is old enough to be mobile and choose which toys to play with (boys choose fire
trucks, etc., girls choose dolls, etc.)
♂
Toy
preference
♀
Normal ♀
Normal ♂
PAH ♀
PAH ♂
CAH females choose more masculine toys than their normal sisters but less masculine
than their brothers
CAH males were just like their normal brothers – not over-masculinized by excess
androgens
~ age 13, CAH females tended to be tomboyish, aggressive, ‘masculine’, while CAH
males are indistinguishable from normal males
it is suggested that this is the result of excessive prenatal androgens