Biological Science 14 (Genetics)

Genetics 

Day 24:

A. Mendelian Concepts

The Father of Genetics: Gergor Mendel (1822-1884) ^[1] 

1. Phenotype and Genotype (Definitions, Probability Calculations, Pedigree Analysis)
Definitions:

• Phenotype is the gene that is used/observed. Ex. I have brown hair.
• Genotype is the genes that are carried. Genotypes can be written as dominant and non-dominant using capital and lower case letters: TT (homozygous dominant), Tt (heterozygous) and tt (homozygous recessive), or as two different equally dominant genes A1A2 (heterozygous for A1 and A2), A1A1 (homozygous for A1), A2A2 (homozygous for A2). Ex. I probably carry the genes for brown and black hair (I am heterozygous for hair color). Since my father and both his parents have black hair, I think he is homozygous for black hair. Having only black hair genes my father must have passed a black hair gene to me. Since I have visible brown hair (therefore having a brown hair gene), but also carry a black hair gene I am heterozygous. My children may have black or brown hair from my side.

Probability:

• Both parents can contribute either of their genes (odds are equal between all genes the parents carry). Ex. I may pass on brown or black hair. If someone has two genes for black hair (homozygous, same genes), they can pass on either gene, but both will be black (there may still be a difference between the black hair genes if one carries a disease or malfunction). 
• There is an equal chance of passing on either gene. The pink flowers below will pass on red 50% of the time and white 50% of the time. Statistically I should pass on brown hair 50% of the time and black hair 50% of the time, but in reality I may happen to pass on one hair color over and over (just due to random chance). The probability for two parents that are heterozygous is: 50% mixed (heterozygous) children, 25% pure (homozygous) children of one hair color, and 25% pure (homozygous) children of the other color. There are two genes for hair, one controls level of darkens (blond, brown and black) and one controls level of red. Brown hair is dominant, black is less stable then brown, blond is recessive. Red is also recessive.

Incomplete Dominance in Flowers of Mirabilis Jalapa) ^[2] 

Calculations: 

• To make a Punnett Square the genes of both parents' genes are lined up (one on the top and one on the left side). The genes get copied into boxes under and across. The offspring of a certain type are counted and divided by the number of boxes (usually 4) to find a percent. For genotype the same letters of the genes are counted, for phenotype expression is counted, that is any box with a dominant letter (one or two) counts as a dominant offspring and double recessive letters count as a recessive offspring.
• In the example below one parent has two recessive genes (green) the result is 1:1. 
• If both parents were hybrids (monohybrid cross) the result is 3:1 (25% pure dominant, 50% mixed, 25% recessive; note that 75% show the dominant trait and 25% show the recessive trait). 
• If both parents were hybrids in a two gene system (dihybrid cross) the result is 9:3:3:1 (9/16 -> 56% show double dominant, 3/16 -> 19% show one dominant trait and one recessive, 19% show the opposite dominant trait and the opposite recessive, 1/16 -> 6% show both recessive traits.

Punnett Square (Easy Calculation Method) ^[3] 

Pedigree Analysis:

• The idea of pedigree is to determine whether genes are recessive or dominant by looking at breeding history and traits of offspring. A simple chart is made using phenotype. Genotype can be inferred depending on what information is present.

Pedigree Symbols ^[4]

Pedigree of My Family's Hair Color: Generation I is My Grandparents, Generation II is My Parents Generation III is My Generation. 

• Other then looking up on the internet that brown hair is dominant, it is easy to tell based on my family history. My mother's father had dark blond hair, my mother's mother had auburn hair (brown component). All their children had brown hair. Brown showed dominance over blond in the II generation. My mother has brown hair and my father has black hair. All their children have brown hair. Brown showed dominance over black in the III generation. I know that my brown hair comes from my mother's side, since my father's side has none. It is extremely likely that I carry a black hair gene, since my father would only show black hair if he carried black and black or black and blond. There are 0 blonds on my father's side of the family for 6 generations, so it is highly likely he carries black and black. My phenotype is brown and my genotype is brown and black. 
• My mother's mother had red (auburn) hair, there is a 100% chance she passed it to my mother (since she only red hair genes), there is a 50% chance my mother passed the gene to me. Hypothetically, if I had children with someone expressing red hair (someone showing red hair has double genes for red hair, since it is recessive) if I do carry the red hair gene 50% of the children would have red hair and 50% would not have red hair. If I do not carry the red hair gene (50% likely) then none of the children would express red hair (even though they would all carry it from the father's side). 
• There are 2 other genes for presence of grey hair. No gene is currently known that explains why hair color changes with age. I was born with black hair and my sister with red-blond hair, but both ended up brown (possibly dominant genes take time to exert control?). Pedigrees and Punnett Squares work best for traits that are not linked to the same chromosome and have few genes controlling them (1-2).

Human Eye Color is Complex, Controlled by at Least 15 Genes ^[5]

2. Gene
A gene is a piece of DNA that has the information of one trait. The DNA is a specific blueprint used to build a protein that will result in a trait. Hypothetical example, a yard can have either a gazebo or a pool or a barbecue area (only one), the blueprints for the whole house would be DNA, the blue prints for just the gazebo, the pool or the barbecue area are a gene, the building materials would be proteins and the final product (the gazebo, pool or barbecue area) is the trait.


3. Locus
The location of a specific gene on a chromosome. Like a page of a book containing the information for a specific information in question.


4. Allele (Single, Multiple)

• Alleles are like ice-cream flavors.
• There are two alleles for each gene, one from each parents. These can be different or the same. I have different alleles for hair color, one black and one brown. My father has the same alleles for hair color, two black alleles. 
• Genes can have more then two alleles. Cells can only hold two alleles (two scoops of ice-cream each, but any combination of flavors). Blood type has three possible alleles (I^A, I^B, and i). Since the body can only hold 2 alleles, multiple blood types are created. Blood type A is: I^A and I^A, or I^A and i. Blood type B is: I^B and I^B, or I^B and i. Blood type O is: i and i. Blood type AB is: I^A and I^B. Japan and South Korea relate personality to blood type. There is even blood type harassment (burahara). I am blood type A: conservative (no), introverted (yes), reserved (no), patient (yes), a perfectionist (yes), obsessive (no), self-conscious (no), uptight (no) and stubborn (yes, very much). 44% Correct, doesn't seem very accurate to me. My mother is also A, her personality is 11%. Type B is supposed to be forgetful, irresponsible, creative, flexible, individualistic, optimistic and passionate. Type O is supposed to be arrogant, insensitive, vain, ambitious, self-confident and robust. My dad is type O, his personality is only 33% correct. My best friend is also O, his personality is only 50% correct. Type AB is supposed to be critical, indecisive, unforgiving, aloof, cool, controlled, introverted and rational. 11%, 33%, 44%, 50% -> F, F, F and F+. Overall it doesn't seem like the system is accurate, based on people I know. I'm calling bullshit, on blood type affecting personality. 

My Family Blood-Type Pedigree

5. Homozygosity and Heterozygosity
Homozygous: having the same alleles for a gene (ii)
Heterozygous: having differing alleles for a gene (i and I^B)


6. Wild Type
The most common type of allele for an organism. Cows are usually colored, white cows are rare. Color is the wild type for cows. The wild type, for humans in Asia, is black hair and brown eyes.


7. Recessiveness
Genes that are not shown unless they are both the same, these genes are overpowered when other genes are present. Blond and red hair are recessive. Black hair is dominant to blond, but recessive to brown.


8. Complete Dominance
Complete dominance means that a recessive trait is not used at all when a dominant allele is present, and the dominant trait is expressed completely.


9. Codominance
Codominance describes two alleles that are equally dominant, both will be used like AB blood type producing A and B antigens.


10. Incomplete Dominance, Leakage, Penetrance, Expressivity

• Incomplete dominance is shown in the pink flowers that are offspring of red and white flowers. Even though the red allele is dominant, it is not dominant enough to totally suppress the white allele.
• Leakage refers to gene flow from one species to another.
• Penetrace is the strength of expression in a gene. If you have a cancer gene, it does not mean you will develop cancer. The amount that a gene really does what it is supposed to is penetrance.
• Expressivity is the amount that a gene is expressed. I have 0% expressivity for red hair, red haired people have <0%. Genes can be expressed to varying degrees.

11. Gene Pool
The gene pool refers to all the possible alleles in a population. A large gene pool is healthy. Small gene pools begin to develop recessive diseases.

B. Meiosis and Genetic Variability

Mitosis creates two identical daughter cells, but meiosis creates a multitude of different daughter cells.

Meiosis Video ^[6]

1. Significance of Meiosis
The process of meiosis allows crossing-over and independent assortment, which lead to variety in daughter cells. Without meiosis all offspring would be the same, evolution would be limited, the species would be more likely to become extinct.


2. Important Differences Between Meiosis and Mitosis
Meiosis forms tetrads (the matching chromosomes pair up and swap genes, called crossing over). In meiosis the resulting cells are different then the parent cell, and contain half the normal amount of DNA (one allele for each gene, instead of two). Meiosis has two divisions and produces 4 sperm or 1 egg and 3 polar bodies.


3. Segregation of Genes
Genes are given opportunities to swap locations (ending up in different cells), genes from each parent are separated randomly into different daughter cells.


A. Independent Assortment
Depending on if each gene is on the left or right side of the cell during metaphase I, the gene will be pulled into the left or right daughter cell.


B. Linkage
Another factor that complicated genetics even more (that Mendel was unaware of) is that genes on the same chromosome are linked (usual stay and occur together). Red hair and freckles seem to be linked. The closer in physical proximity on the chromosome, the less crossing over effects linkage. The genes furthest away from each other are the most likely to end up on opposite chromosomes, genes right next to each other will more then likely remain next to one another.


C. Recombination
Recombination means changing up the genes in new combinations, which refers to both independent assortment and crossing over.


D. Single Crossovers
Crossing over happens during prophase I, when a synapsis forms a tetrad out of homologous chromosomes, which form a chiasma (the site of crossing over). Independent assortment is the sorting of one chromosome each into the two daughter cells. ^[7]


E. Double Crossovers
If chromatids exchange exactly the same genes twice no genetic recombination has occurred. If chromatids exchange and then one of them exchanges with a different chromatids (3-strand double crossover) recombination occurs. If chromatids exchange and then both of them exchange with different chromatids (4-strand double crossover) double the recombination occurs. ^[7]


4. Sex-Linked Characteristics
Human females have two X chromosomes, males have one X and one y. The genes below would belong to a male.

Human X and Y Chromosome ^[8]

A. Very Few Genes on Y Chromosome
The y chromosome is too small to fit much. The vital genes are usually put on the X chromosome.


B. Sex Determination
XX -> Female 
Xy -> Male


C. Cytoplasmic Inheritance, Mitochondrial Inheritance
All cytoplasmic contents such as mitochondria and organelles are inherited from the mother (because they fit in the egg, but not the sperm). Therefore, any mitochondrian defects are from the mother's side.


5. Mutation
Errors occur in DNA. Turtles become ninja turtles...


A. General Concept of Mutation
Mutation can be a good thing, because it leads to variety in small populations. Or it can be a bad thing that causes disease or death.


B. Types of Mutations (Random, Translation Error, Transcription Error, Base Substitution, Insertion, Deletion, Frameshift)

• Random Mutations: UV radiation, chemicals and replication errors cause mutation.
• Translation Error Mutations: Errors can occur during the translation into protein.
• Transcriptional Error Mutations: Errors can occur during transcription into mRNA.
• Base Substitutions Mutations: A base pair is switched on accident.
• Insertion Mutations: A base pair is accidentally added, lengthening the sequence.
• Deletion Mutations: A base pair is accidentally removed, shortening the sequence.
• Frameshift Mutations: Three bases are messed up, therefore different amino acids are coded.

C. Chromosomal Rearrangements (Inversion, Translocation)
The chromosomes can break and rearrange itself end to end (inversion) or can move and reattach in another location (translocation).


D. Advantageous Versus Deleterious Mutation
Advantageous Mutation -> Improvement 
Deleterious Mutation -> Harmful 


E. Inborn Errors of Metabolism
Errors of metabolism caused by genes.


F. Relationship of Mutagens to Carcinogens
A mutagen causes mutation, a carcinogen causes cancer. Carcinogens are often mutagens. Mutagens may or may not by carcinogens.

C. Analytic Methods

The method for determining genetic shift is by measuring the amount of alleles within a population and seeing if they change or remain the same.


1. Hardy–Weinberg Principle
Mendelian genetics shows a normal ration of dominant and recessive alleles are passed down to future generations. A dihybrid cross produces offspring with the ratio 9:3:3:1. That concept developed into the Hardy-Weinberg Principle:







p² + 2pq + q² = 1 

and 

p + q = 1

P: the Dominant Allele

q: the Recessive Allele

p² = percentage of homozygous dominant individuals

q² = percentage of homozygous recessive individuals

2pq = percentage of heterozygous individuals

There are five rules to using the Hardy-Weinberg Principle:

1. No mutations must occur so that new alleles do not enter the population.

2. No gene flow can occur (migration).

3. Random mating must occur (individuals must pair by chance).

4. The population must be large so that no genetic drift (random chance) can cause the allele  frequencies to change.

5. No selection can occur so that certain alleles are not selected for, or against.

 ^[7]

2. Testcross (Backcross; Concepts of Parental, F1, and F2 Generations)

• The testcross is the way to tell what hidden genes are carried, but not expressed. By breeding a dominant phenotype with a recessive phenotype and observing the offspring (half recessive or all dominant), it is possible to tell if the dominant subject was double dominant or only single dominant. 
• Ex. I have brown hair, if I have children with someone with black hair, and the children have black hair, then I am heterozygous dominant. 
• Backcross is mating between offspring and parent.
• P represents parent, F1 (filial 1) represents the children and F2 represents the grandchildren.

Footnotes:
1. Gregor Mendel. Drawing. Universität Hamburg. [Online]. Jul 31, 2003
http://www.biologie.uni-hamburg.de/b-online/e08/08a.htm (retrieved Jul 3, 2012).


2. Correns, C. Incomplete Dominance in Flowers of Mirabilis Jalapa. Drawing. Universität Hamburg. [Online]. July 31, 2003
http://www.biologie.uni-hamburg.de/b-online/e08/08a.htm (retrieved Jul 3, 2012).


3. Punnett Square. Drawing. Wilipedia. [Online]. Oct 18, 2008.  
http://en.wikipedia.org/wiki/File:Punnett_Square.svg (retrieved Jul 3, 2012). 


4. McClean, P. Pedigree Symbols. Drawing. Mendelian Genetics. [Online]. 2000. 
http://www.ndsu.edu/pubweb/~mcclean/plsc431/mendel/mendel9.htm (retrieved Jul 03, 2012).


5. Human Iris. Photograph. Wilipedia. [Online]. Mar 26 2012.  
http://en.wikipedia.org/wiki/Eye_color (retrieved Jul 3, 2012). 


6. Meiosis. [Video]. Pearson. [Online]. 2007.
http://www.youtube.com/watch?feature=player_embedded&v=kVMb4Js99tA (retrieved Jul 03, 2012).


7. Genetics. MCATReview.org [Online]. 2008.
http://mcat-review.org/genetics.php (accessed Jul 03, 2012).


8. Richardson. X and Y Chromosomes. Photograph. Biol 1020 Genetics Blog. [Online]. 2012.
http://biol1020-2012-1.blogspot.com/2012/05/y-men-are-no-longer-set-for-extinction.html (accessed Jul 03, 2012).