PSYC 3102: Introduction to Behavioral Genetics

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 normal

low IQ high 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 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