Mendelian¹ Patterns of Inheritance and Human Genetics 

I. Gregor Mendel is considered the father of genetics

The Austrian monk Gregor Mendel founded the early principles of genetics in 1866. Apparently, nobody during his time understood his work. With the study of chromosomes in the early 1900's Mendel's work found a new audience, one that understood the significance of his earlier findings. Today, geneticists have a far more complete understanding of inheritance. To begin, we know that genes occur in pairs in diploid organisms. Of course the only time genes literally “pair up” is during synapsis of meiosis when the homologous chromosomes that carry the genes pair up. A gene pair is represented by two alleles such as AA (homozygous dominant), aa (homozygous recessive), and Aa (heterozygous).² A gene is a portion, segment, of the DNA molecule found in, or on, a chromosome. We use the term allele when we wish to refer a specific form of a gene. “A” and “a” for example represent different forms (alleles) of the same gene.  

In 1866 Gregor Mendel proposed what was to become the foundation of genetics. Mendel was completely unaware of our modern concept of the gene and that gene pairs are separated during the cellular event called meiosis. But nonetheless, while working with garden peas Mendel was able to deduce that genes (he called them “factors”) occurred in pairs and that they “assorted” or “segregated” and then recombined during sexual reproduction. We now know that assortment or segregation occurs during meiosis and recombination occurs during fertilization.  Today it is convenient to use the Punnett-square method to predict inheritance based on these simple principles. Restated differently, the principles behind the Punnett-square are these:  
· Gene pairs segregate during meiosis such that each haploid daughter cell gets only one of the two possible alleles. Gametes carry only one allele from each gene pair. Gametes from a given parent can only carry one of the alleles possessed by that parent. If the parent is homozygous, then the gametes produced are all identical. For ex. if the parent is “AA” then the gamete can only be “A.” Each possible type of gamete produced from a parent is written along one side of the Punnett-square.  
· Genetic Recombination. Through fertilization haploid gametes fuse recombining the gene pairs into a diploid zygote. In the zygote (the next generation) the alleles of the gene pair will likely occur in new combinations as compared to either parent. Recombination of alleles (genetic recombination) is symbolized by filling in the little boxes of the Punnett-square.  Punnett-squares are part of a lab exercise you have completed by now.

¹ “Mendelian” refers to a trait that is controlled by only 1 gene pair with dominant /recessive alleles.
²We refer to such representations as the genotype (combination of alleles present).

 
II. Beyond Mendel
A. The environment also determines the expression of traits.

For most inheritance, genetics is quite a bit more complex than the Mendelian pattern. In part, this is because genes are not the only factors that determine the expression of traits. The phenotype (appearance) of a given trait or characteristic is greatly influenced not only by specific alleles inherited but also by environmental factors.
Phenotype = appearance and is determined by: 1. Genetic makeup (=genotype)    and   2. the Environment 
As an example of the environmental effect on phenotype consider:  
a) nutrition affects height
b) for social insects food feed while young makes a young bee either a worker or a queen
Thus, not all conditions can be attributed to genetic factors. Poorly understood diseases, many birth defects may be due to environmental factors rather than inheritance.

B. Dominance Relations (Allelic Interactions)

1. Dominant / Recessive – The dominant allele completely masks the expression of the recessive allele. 2. Incomplete Dominance – The ~dominant allele partially masks the expression of the ~recessive allele. 
Ex. snapdragon flower color, heterozygotes have intermediate phenotype. 3. Codominance - both alleles expressed fully in the heterozygote ex. AB blood types

C. Multiple Alleles - one gene has more than two possible forms (when 3 or more alleles exists for a gene pair). Ex, I^A, I^B, and i
        (see lab manual for all possible genotypes & phenotypes for ABO blood types)

D. Polygenic Inheritance - more than one gene pair influences a trait; results in a range of phenotypes.

Comparison of traits between individuals for traits governed by a single gene pair reveals discontinuous variation, ex. tongue rolling, either you can or you can’t, only 2 phenotypes, no intermediates. But most traits exhibit continuous variation- a range of phenotypes for a given trait, that is there are many possible phenotypes, not just two or three. Continuous variation is a result of polygenic inheritance - when two or more gene pairs control a single trait.  depicting the variation in traits under polygenic control).  Skin color is another example of a trait under polygenic inheritance. Darkness of skin color is determined by the production of the pigment melanin. Consider this simplified example: Two genes, A & B, contribute to melanin production. Only the alleles represented by capital letters contribute to melanin production. Each person has four alleles (two gene pairs) so the following are possible.
Genotype Phenotype    
AABB Very dark    
AaBB or AABb Dark                
AaBb or aaBB or Aabb    Medium             
Aabb or aaBb light             
aabb                      very light
Continuous variation is exhibited in the variation range along the "continuum" from "very dark" to "very light"

E. Gene expression can be affected by external factors (the environment) [see also A. above]

ex. Siamese Cats & Himalayan rabbits - have dark fur on extremities, It has been demonstrated that lower skin temperature activates a gene for pigment production.
ex. Diet affects an individual’s size and health [malnourishment results in shorter height thus, genes + environment => phenotype]

III.  Chromosomes and Human Genetic Disorders

A. Human Autosomal Disorders

1. sickle-cell anemia - to understand this disease you must know that the gene involved is for hemoglobin production within red blood cells (RBC).  The gene has two alleles:  Hb^N - normal hemoglobin & Hb^S - abnormal hemoglobin that fails to support the shape of RBC's.  The disease is recessive, yet the alleles are codominate (heterozygotes will have both normal and abnormal hemoglobin).   Below are all possible genotypes for this gene pair.
Hb^NHb^N - normal
Hb^NHb^S - normal but some sickle cells [malaria protection]
because malaria parasite cannot reproduce in sickle cells, infection not as severe
Hb^SHb^S - sickle cells disease.
anemic symptoms, kidney failure, heart failure, abdominal pain (many others)

2. PKU or Phenylketonuria - inability to metabolize excess amounts of the amino acid phenylalanine, can result in mental retardation.  Gene "A" controls our ability to eliminate excess phenylalanine and the alleles are:
A - dominant & normal 
a - recessive & defective
Most of us have no problem getting rid of excess phenlylalanine.
We are AA - normal or Aa - normal, but a carrier
If this gene doesn't function normally an abnormal, toxic pheynlketone builds up, this disrupts development of the nervous system.
100% treatable by restricting diet, very limited amounts of phenylalanine [no artificial sweetener, no aspartame which contains phenylalanine] [see warning label on diet soda can]
In the U.S., infants are genetically screened for PKU. (1 in 10,000)

3.  Cystic fibrosis - a recessive disease in which a faulty protein is implicated as the cause of the disease.  The faulty protein fails to transport Cl^- ions across membranes and this then leads to thick mucus lining the air sacs of the lungs and elsewhere.  A gene is responsible for the blueprint instructions from which the  Cl^- ion transport protein is made. 

Hypothetical Note:  Given our understanding of why sickle cell disease and the allele that causes it is so frequent and historically restricted to races living in the Old World Tropics (e.g. the "bad" allele serves to protect one from malaria and was historically found in those regions where humans have lived with the malarial parasite for many thousands of years), the high incidence or cystic fibrosis and PKU may be due to a heterozygote advantage, that is, heterozgotes that carry the "abnomal" allele may in fact enjoy greater survivability and reproductive success under some as of yet unknown circumstance.

4. Huntington disease -
Disease which destroys the brain of the middle-aged, determined by gene A - dominant & defective a - recessive & normal.
aa - most of us 
Aa - 1/10,000 Huntington Disease 
AA - die as embryos
on chromosome #4.
loss of muscle control and mental function - particularly insidious because disease doesn't make itself known until after the age at which you can have children. If you have Huntington Disease, what is the chance of passing the disease on to your children if your spouse is normal?

Another lesson from Huntington disease, is that it is not necessarily inherited along family lines.  It often appears anew, resulting from spontaneous mutation during conception or early embryonic development.  The idea that new alleles can appear as a result of mutation is an important one in understanding evolution by means of natural selection.

B.  Sex Determination
Ask for sex chromosomes of male and female and you get XY for males and XX for females.
What is the control that tells the human embryo to become male of female? What influences an undifferentiated gonad to become a testis or an ovary?
Humans and many other animals have a gene on the Y chromosome for maleness (SRY gene).  In the absence of SRY gene many animals become females.  The sex chromosomes primarily possess genes that govern nonsexual traits, at least this is true for the more than 2,000 genes found on the X chromosome where important instructions for vital processes are found (e.g. instructions for synthesizing blood clotting proteins are found on the X chromosome). 

Humans normally have 46 chromosomes, 44 are autosomes - non sex chromosomes, and 2 are sex chromosomes - XX or XY

Sex Chromosomes are Not Universal.
For some reptiles temperature not sex chromosomes, influence the sex of the developing embryo.
ex. consider the alligator, female lays eggs in nest of rotting vegetation, this helps incubate the eggs.
eggs @ 38 C - all become male
eggs @ 20 C - all become female
this is also another example of gene expression affected by environmental factors.
Hermaphrodites - ex. slugs, earthworms, are both male and female in the same body and sex chromosomes are meaningless and not present in such organisms..

C.  Abnormal Chromosome Numbers in Humans

Aneuploidy - having lost or gained an extra chromosome when conceived; 2n +1 or 2n - 1
2n - 1 is the aneuploid condition in Turner Syndrome or XO in which an individual has only 45 chromosomes and is missing a sex chromosome.
2n + 1 yields 47 chromosomes w/an extra sex chromosome in the following "disorders"
XXY - Klinefelter Syndrome
XYY - Super male Syndorme

2n + 1 is also the aneuploid condition of Trisomy 21, Down Syndrome

What leads to changes in chromosome number?
NONDISJUNCTION - failure of synapsed pairs of homologues to separate during meiosis; leads to gametes w/too many or too few chromosomes.
Ex. of extreme nondisjunction is when meiosis fails and gametes are diploid
2n egg + 1n sperm = 3n, or triploid

The phenomenon of having 3 or more complete sets of chromosomes in a nucleus is called POLYPLOIDY
Human polyploid embryos spontaneously abort
Polyploidy is common in plants and has given us important cultivars among crops.  It is also common in nature and leads to new species creation (i.e. speciation).