Complex Inheritance

Non-Mendelian Inheritance

Complex genetics are systems of inheritance that don’t follow the dominant/recessive system that Mendel found in his pea plants.   You have to remember that meiosis and fertilization occurs the same, but the relationship among the alleles is not the same.  For example, instead of a heterozygote having the same phenotype as the homozygous dominant, it may have its own phenotype.  This is like a red and a white flower making pink flowers.  There can also be more than just the two alleles that Mendel found.  Blood types, for example, have more than just two alleles. 

It is these system of inheritance that most human genetics follows.  We have very few traits that are dominant/recessive, well, very few that matter.

Incomplete dominance

The first non-Mendelian system is called incomplete dominance.  Just like Mendel’s system, there are two alleles, but they interact differently.  It is tempting to apply the words dominant and recessive to this system.  In factA statement based on direct observation that is repeatedly confirmed., this picture here uses the capital and lowercase R and r.  Don’t be fooled.  We could use two different letters here and it wouldn’t matter.  This is because the heterozygote has its own phenotype in this system of inheritance.  Unlike Mendel’s genetics, one of the alleles does not mask the appearance of the other alleleDifferent versions of a gene that determine specific traits..  The heterozygote has a phenotype that is usually intermediate to that of the other two.  In this example here, there is an allele for a red flower.  When you have two of those alleles, you get a red flower.  There is also an allele for a white flower.  When you get two of those you get a white flower.  However, when you get one of each of these alleles you get a color between the two: pink

Incomplete dominance

Humans have a few systems of incomplete dominance.  This is true for the genes that control cholesterolA lipid molecule that is a key component of cell membranes and a precursor for bile acids and steroi management.  Your cellsThe basic structural and functional units of life., especially the ones in the liverA large organ that produces bile, detoxifies blood, and stores nutrients., make proteinsLarge molecules made of amino acids with various functions in the body. that go into their cell membranes and attach to LDL, a type of cholesterol.  As shown in the picture on the left, if you get two HH alleles, you make these proteins and they bind up the LDL cholesterol.  That’s great because then the cholesterol isn’t floating around in your blood and clogging your arteriesBlood vessels that carry oxygenated blood away from the heart (except pulmonary arteries, which carr.  There is also another allele referred to as lowercase h in the picture above.  Again, don’t be fooled, just because we are using the capital and lowercase letters, we are not indicating dominant or recessive.  If you inherit one of each of these alleles, you still make the protein, but not a lot of it.  As shown in the picture in the middle, you have receptorsProteins located on the surface or inside cells that bind specific molecules (e.g., neurotransmitter, they bind the LDL, but you will still have an overabundance of LDL in your blood.  Luckily, this can be managed with a healthy lifestyle, good food choices, and exercise.  In fact, many people who are heterozygotes with this condition don’t know it until they get a little older. 

Unfortunately if you inherit two of the lowercase r alleles, you have no ability to bind cholesterol.  This can create problems in young children and adolescents as they are accumulating cholesterol build up in their arteries from day one.  These people don’t make the receptors and thus have no ability to bind the free floating LDL in the blood.  This can be managed if you know you have it, but most people are not tested for this disease unless you are certain that someone else in your family has it.

Sickle Cell Anemia can be considered incomplete dominance

Sickle cell anemiaA condition characterized by a deficiency of red blood cells or hemoglobin, leading to reduced oxyge is also incomplete dominance.  If often is incorrectly referred to as dominant and recessive, but it is actually incomplete dominance.  There are two alleles for the shape of the hemoglobinThe oxygen-carrying protein in red blood cells that gives blood its red color. protein.  If you receive two alleles that make hemoglobin correctly, your red blood cells are like those round ones in the picture there.  These roundish cells have a shape called bioconcave.  This shape is ideal for carrying oxygen and carrying as much of it as it can.  People with two of these alleles do not have sickle cell anemia.  There is also an allele that make hemoglobin, but the protein is misshapen.  This incorrect shape results in red blood cells being sickle cells, or crescent shaped.  This shape is not ideal for carrying oxygen.  It can carry it, but just not as much as the bioconcave shapes.  The amount of oxygen it carries is also not enough for the tissues of the body.  Thus, this results in anemia, which is a deficiency of red blood cells.  There are many different types of anemia, but this type is genetic and this type affects the shape. There are no people with two of these alleles.  Fetuses with two diseased alleles do not make it to birth.  In early developmentThe process of growth and differentiation., the cardiovascular systemThe organ system that includes the heart and blood vessels, responsible for circulating blood and ox develops and is incapable of servicing the growing fetus.  However, there are people who have one of each of these alleles.  These heterozygotes express the sickle cell anemia disease.  Many times, healthy people with this disease may not feel the effects of it until later on in life.  You might expect these people to have a 50/50 split of bioconcave and sickled red blood cells but the immune system actually tips that balance to 40/60 with the bioconcave cells amounting to about 60% of the circulating red blood cells. 

Sickled red blood cells are incapable of being infected with malaria.  In regions of the world where malaria is common, people with this disease live longer and reproduce more.  People with the bioconcave red blood cells that get infected with malaria can die.  These days, thanks to modern medicine, that’s not exactly true, but these people are at a greater risk.  This map here shows you that in areas with high incidence of malaria, there is also a high incidence of people with sickle cell anemia.  So, it pays to have diseases sometimes.  But, in areas where there is no malaria present, it pays to have bioconcave cells.  It all depends on the surrounding environment.

Multiple Alleles

I can’t remember why I put this picture of the rabbit here.  I left it in there because it is cute and fuzzy.  Probably soft too.

Regarding genetics, there is a situation where you can have more than just two alleles.  In Mendel’s genetics we only had two variants of a gene: the dominant allele and the recessive allele.  In multiple alleles, we have three or more.  Blood types is a great example of multiple alleles because it has three alleles.  This results in 4 different blood types: O, A, B, and AB.  The ABO system of inhertaince for blood indicates what type of proteins are inserted into the cell membranes of the red blood cells.  For example, people with type O have no proteins in their red blood cell membranes and people with AB have two different proteins (A and B).  Type A and Type B are a little more complicated to explain. 

The system of inheritance that determines if you are positive or negative is a completely different system.  In fact, being type O has no bearing on whether or not you are positive or negative.  These two traits are completely unrelated kind of like inheriting the ability to metabolize cholesterol has nothing to do with your eye color.  Or, at least, I don’t think it does.  I’ll have to look that up!

Multiple alleles

When we have three alleles, we usually use a superscript as you see above.  The uppercase I and the lowercase i tell us that all these are variations of the same gene.  There are three variations here.  One allele gives you the power to have the A protein, noted by the little yellow triangles in the picture.  Another allele gives you the power to have B type prtein, indicated by the yellow circles in the picture.  What, then is the lowercase i?  It’s a place holder.  This is an allele that basically says: don’t make a protein. 

Blood Types are also Codominant

In addition to being a case of multiple alleles, blood types are also codominant.  This means that the heterozygote has a phenotype that express both alleles it inherits.  This picture here of the fish is a perfect example of this.  If a red and a blue fish mate, they don’t make a purple fish. That would be incomplete dominance.  Instead, they produce a fish that has both red and blue coloring.  This means that both alleles are expressed and coloration is codominant.  Blood types are also codominant.  This is exemplified by the Type AB people.  They have both the A protein and the B protein expressed in their red blood cells.

Pleiotropy

The next two slides are the opposite of each other.  Pleitropy is a situation where one allele, something like a master allele reaching out and influences other genes.  Human albinos are an example of this.  There is a gene for albinism.  When it gets  passed on, it reaches out and turns off other pigmentation genes.  Even though these people might have the ability to make the skinThe body’s largest organ, providing protection and regulation. pigment melaninA brown-black pigment made by melanocytes in the stratum basal and given to keratinocytes as melanos, they don’t.  That gene is prevented from being expressed.  It’s as if the albino allele has turned off the other genes.  This goat here is actually not an albino.  It’s just a recessive white goat.  Many years ago, there was a population of white deer in the Seneca depot over between Seneca and Cayuga lakes.  There were white deer in the dopt and they were incorrectly referred to as albinos.  White is just a recessive trait for coat color in deer.

polygenics

Opposite to one master gene affect others, polygenics is when there are many genes influencing one trait.  Many pigmentation genes work together to create eye color, hair color, and skin color.  This is why there are so many different variants of these pigmentation states.  This also creates a fluid spectrum of phenotypes that can sometimes be difficult to tell apart since they are just all slightly different from others.  The next slide gives you a visual on skin color as an example.

Polygenics – many genes one trait

This isn’t exactly how skin color is inherited, but let’s use it as an example.  Let’s assume that you have three genes that work together to create skin color.  Each gene has two allele that interact in a dominant/recessive fashion.  One allele says to make melanin and the other allele says not to make melanin.  Again, we have three genes so that means that we have a total of 6 alleles that combine to make skin color.  This huge Punnett square above could use letters, but I love that it gives you the visual of the six alleles, all of which can be black (make melanin) or white (don’t make melanin).  Look at how this creates a huge spectrum.  The most common combination of alleles is having 3 that make melanin and 3 that don’t.  The most infrequent combinations are all recessive or all dominant.  This relationship creates a bell curve of the frequency of skin colors.  This is like the distribution of grades in a class where very few people get 100s, very few people get 60s and most students are in the 80s range.