Download PSYC 3102: Introduction to Behavioral Genetics

PSYC 3102: Introduction to Behavioral Genetics
Lecture 7
Test will be through Mendelian Disorders
Last time: Testosterone levels respond to external stimuli, testosterone enhances or inhibits
transcription
Another example:
Cortisol (in book)
 You don’t need to know details, but read about it in the text
 Key idea: a large number of genes can be affected
 Normal secretions occur everyday, but is very sensitive to stress (physical or psychological)
 Cortisol ‘slips’ into cells and binds with receptor, then turns genes on or off
Hormones are a large class of molecules that influence genetic expression
Genetics and Development:
i.e. Why do we have heads and butts?
We are organisms composed of LOTS of cells
Some cells need to develop into the head, arms, torso, eyeballs, etc.
Important Series of Genes:
Homeobox- series of genes with very similar nucleotide sequences
Hox gene- a particular type of homeobox responsible for development
 gene products are transcription factors with enhance and/or inhibit gene expression
 Developing organism is given polarity by Hox genes
 Hox 1 & 2 are turned on to differentiate cells of the head area
 Then 1& 2 are turned off, and 3& 4 are turned on to differentiate cells of the middle
area
 Then 3 & 4 are turned off, and 5 & 6 are turned on the differentiate cells of the hind
area
Hox 1
Hox 2
Hox 3
Hox 4
Hox 5
Hox 6
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This begins early in development
Hox genes are strongly conserved over evolution
Consequently many human segments are virtually identical to those in a fuit fly
In the past this was studied by knocking out a hox gene in another species and inserting a
human hox gene
Strong homology persists through evolution, indicating that it is a very important system
It is thought that mutations in these genes are deleterious and cause lethality
Once a cell is differentiated it doesn’t go back to being undifferentiated
Sexual Differentiation
Xy
XX
 Natural course of human sexual development is in a female direction
 Males are basically androgynized females
 Around the 2nd month of development the beginnings of internal gonads develop (same in
XX and Xy)
 Following this, the XX organisms go on to develop ovaries, uterus and external genitalia
(indoor plumbing)
 Meanwhile in Xy organisms the SRY gene ‘turns on’ (is expressed), which in turn enhances
expression (turns on) genes that produce androgen hormones and genes that produce
androgen receptors
 Testosterone enhances/inhibits expression of other genes, and testes, penis, etc. are
developed (outdoor plumbing)
 SRY=Sex Determining Region of the Y chromosome
 Genes for androgen receptors are on the X chromosome
 If one has a ‘bad’ X, and receptor is not produced properly, no binding can occur
o In this case an Xy can develop as normal (but infertile) females
 Another IMPORTANT issue: This is not just limited to sexual organs, the presence of
androgens and androgen receptors affect other parts of the body as well (ex: BRAIN)
Mendelian Disorders / Traits
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most Mendelian disorders occur in 1 out of 10’s of thousands of births
PKU – phenyketonurea
Involves a metabolic pathway
Phenylalanine and tyrosine are amino acids
We get amino acids from diet, breakdown of our own proteins, or by synthesizing them
Phenylalanine comes only from diet and breaking down our own proteins
Tyrosine comes from diet, breakdown of proteins, or conversion from phenylalanine
PAH = Phenylalanine hydroxylase
Tissue Protiens
Diet
Phenylalanine
PAH
Tyrosine
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There is a gene with a blueprint for phenylalanine hydorxylase
PKU occurs when the PAH enzyme is defective
This causes a block in the metabolic pathway
By products of this block build up
This results in damage in the developing nervous system
Disorders like PKU are called METABOLIC BLOCKS
Enzymes are non-functioning or missing and a build up of precursors in the pathway occurs
In PKU there will not only be a build up of phenylalanine, but also a reduction in tyrosine
Tyrosine gets converted to DOPA, which is converted to melanin and dopamine, so you get
reductions in all of these
Points about PKU
 Babies appear normal at birth
 If undiagnosed and untreated the following symptoms occur
o Motoric problems
o Cognitive difficulties (mental retardation)
o Hypopigmentation (under pigmented)
o High levels of phenylalanine proteins in urine
 Treatment: PKU is the ‘poster child’ of genetics because it has an environmental
treatment/intervention—DIET
Genetics of PKU
 Recessive disorder, needs two ‘bad’ alleles for the PAH enzyme
Genotype
2 good PAH blueprints
X amount of PAH made
1 good/1 bad PAH blueprint
½ X amount of PAH made
2 bad PAH blueprints
0 PAH made
 Many (>400) different ‘bad’ spelling variations (alleles)
o All are very rare
o Allelic Heterogenity
o Usually those with PKU have 2 different variations of the ‘bad’ alleles
 Prevalence: 1/10,000 births
o Higher in Celtic and Scandinavian populations
o Found in all populations, but frequency is higher or lower in some
3 Crucial Ways Genotypes Relate to Phenotypes
1. Penetrance
o Probability of getting a disorder given that one has the gene for the disorder
o If the probability is equal or close to equal to 1 it is fully penetrant
o If the probability is less than 1 it has incomplete penetrance
o Ex: Marfan’s Syndrome involves a dominant gene, but the probability of having
the syndrome is .5
o This is applied ONLY to single gene disorders (Mendelian disorders)
2. Pleiotropism (Pleiotrophy)
o A single gene can influence more than one phenotype
o PKU genotype influences pigmentation, motor system, and cognitive abilites
o Tends to be the norm, probably universal
o Huntington’s: psychiatric disturbances, motor system, dementia
3. Variable Expressivity
o Applies to a continuous or quantitative phenotype (like height)
o All have it, but it there is a range
o Ex: IQ in untreated PKU: Some are in the normal range, but some can’t care for
themselves
frequency
PKU
low
normal
IQ
high
o Often will see in behavioral symptoms/phenotypes
o Most genes have variable expressivity, almost will always see
o Ex: Fragile X – mental retardation variation between normal range and not able
to care for self