Transcript phenylketonuria (PKU): linked to genes on chromosome 12.

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.
PKU
Hair
color
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.
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.
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.
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-16
P-16
THE DNA SEQUENCE
OF THE GENE FOR THE
RECEPTOR MAY
BE DIFFERENT,
BETWEEN THE M COPY
AND THE P COPY
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.
Normal
metabolism
OH
Homework assignment: look up and draw the structures
of the compounds, that appear in the urine during PKU
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.
M-12
P-12
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.