1. DOMINANT AND RECESSIVE TRAITS January 22, 2015 These terms occur very often in the study of genetics. This lecture will deal these topics to give you an overview. We will discuss two kinds of recessive traits: -the first type, tends to refer to harmless traits (blue eyes compared to brown eyes, curly hair, etc). -the second type can be of great medical importance (lack of ability to metabolize phenylalanine) When you read about recessive traits, make sure you know which class of trait is being discussed.

2. We will discuss two recessive traits in this lecture: -blond or red hair: linked to genes on chromosome 16, -phenylketonuria (PKU): linked to genes on chromosome 12. PKU Hair color

3. HAIR COLOR: BROWN/BLACK COMPARED TO RED/BLOND 1)For about 95% of genes (on chromosomes 1-22) you have genes from each parent, and usually if one gene is active in the cell, the other gene is also active. Each gene is producing mRNA, which is then translated to make protein. 2)Genes for melanin production have a very strong effect: if the maternal gene codes for a lot of melanin in the hair, the child will have black or brown hair, even though the gene on the paternal chromosome codes for a different protein 3)Red and blond hair are therefore “recessive”, because the protein from the “dominant” gene is more active than the protein from the “recessive” gene.

4. The MC1R gene provides instructions for making a protein called the melanocortin 1 receptor. This receptor plays an important role in normal pigmentation. The receptor is primarily located on the surface of melanocytes, which are specialized cells that produce a pigment called melanin. Melanin is the substance that gives skin, hair, and eyes their color. THE GENE FOR THE RECEPTOR IS ON CHROMOSOME 16. Melanocytes make two forms of melanin, eumelanin and pheomelanin. The relative amounts of these two pigments help determine the color of a person's hair and skin. People who produce mostly eumelanin tend to have brown or black hair and dark skin that tans easily. People who produce mostly pheomelanin tend to have red (or sometimes blond) hair, freckles, and light-colored skin that tans poorly. Pheomelanin is a compound that gives hair its red color. The melanocortin 1 receptor controls which type of melanin is produced by melanocytes. When the receptor is activated, it triggers a series of chemical reactions inside melanocytes that stimulate these cells to make eumelanin. If the receptor is not activated or is blocked, melanocytes make pheomelanin instead of eumelanin.

5. Common variations (polymorphisms) in the MC1R gene are associated with normal differences in skin and hair color. Certain genetic variations are most common in people with red hair, fair skin, freckles, and an increased sensitivity to sun exposure. These MC1R polymorphisms reduce the ability of the melanocortin 1 receptor to stimulate eumelanin production, causing melanocytes to make mostly pheomelanin. If only ½ of the receptors on the melanocyte activate eumelanin production, enough eumelanin is made to produce black or brown hair. So red hair is recessive, a certain gene for the receptor protein has to be obtained from each parent, to have red hair. M-16P-16 THE DNA SEQUENCE OF THE GENE FOR THE RECEPTOR MAY BE DIFFERENT, BETWEEN THE M COPY AND THE P COPY

6. Phenylketonuria: caused by a recessive gene that can have harmful effects 1)The enzyme Phenylalanine Hydroxylase (see next slides) converts much of our phenylalanine to tyrosine. 2)We have two copies of that gene, on each Chromosome 12. We get one copy from the maternal gene, and one from the paternal gene. In a normal person, usually some protein is being made from each copy of the gene. 3)Suppose one copy is defective, and does not make normal Phenylalanine Hydroxylase? There is no apparent harm, because the GOOD copy makes enough enzyme to prevent any problems. 4)But if you get a BAD copy of the gene from both parents, now you have a problem, and must restrict dietary intake of phenylalanine.

7. OH Normal metabolism

8. Homework assignment: look up and draw the structures of the compounds, that appear in the urine during PKU

9. M-12 P-12 The gene that codes for the protein Phenylalanine Hydroxylase is located on the long arm of Chromosome 12. If the DNA sequence is mutated on both the Maternal and Paternal versions, so that neither gene produces functional enzyme, then the child with have the disorder PKU. But if ONE gene works and makes active enzyme protein, the child will be healthy.

10. NEXT WEEK IN CLASS, WE WILL DISCUSS INHERITANCE, AND HOW IT’S POSSIBLE TO GET A DEFECTIVE COPY OF A GENE FROM BOTH PARENTS. THAT CAN BE A REAL PROBLEM.