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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 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 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 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