Heredity

Designer Genes is a Division C event that is expected to rotate in for the 2019 season. It was previously an event for the 2013 and 2014 seasons. The event covers topics relating to genetics and the molecular biology of inheritance.

DNA
DNA is made up of three components: a phosphate group, a deoxyribose sugar, and heterocyclic rings of carbon and nitrogen (purines have two such rings; pyrimidines, one). The bases found in DNA are adenine and guanine (purines), thymine and cytosine (pyrimidines). The sugar and phosphate groups form the backbone or the sides of the double helix "ladder" and the nitrogenous bases stick out from the chain like "rungs" of the ladder.

Watson, Crick, and Maurice Wilkins are credited with finding the structure of DNA. Rosalind Franklin, however, was the first to use X-ray diffraction to see the DNA helix. Watson and Crick used her work to discover the helical structure in 1953. See The Double Helix by James D. Watson for more information.

Base Pairing
Adenine only bonds with thymine and guanine bonds only with cytosine. This is called base pairing. According to Chargaff's rules, an organism should have equal percentages of adenine and thymine and cytosine and guanine. One way to remember which base pairs with which is to remember the "curvy" letters go together. If Chargaff's rules do not hold, the organism's DNA may be single-stranded rather than double-stranded.

In RNA, uracil replaces thymine and thus, uracil binds with adenine.

DNA Replication
When a cell divides, it makes a duplicate of its DNA in the S-phase of the cell cycle so the daughter cells will have a complete set of chromosomes. This process is DNA replication, also called DNA synthesis. First, topisomerase unwinds the DNA strands, after which the enzyme helicase separates the strands by breaking the hydrogen bonds between nitrogenous bases. This area of separation is called a replication fork.

Before DNA Polymerase can enter the replication fork to make copies of the DNA strands, RNA Primase puts down a "primer" to attract RNA nucleotides, which form hydrogen bonds with DNA bases. The next step is elongation, which creates some difficulties because of how enzymes "read." DNA Polymerase can only copy from 5' to 3'; however, one DNA strand is 3' to 5'. This strand is called the lagging strand, as opposed to the 5'-3' leading strand. While DNA Polymerase can copy the leading strand without a problem, it can only replicate the lagging strand in spurts. The spaces between replicated portions of the lagging strand are called Okazaki fragments.

Once replication is complete, an exonuclease (an enzyme that cleaves nitrogenous bonds) removes the RNA primer. Finally, ligase connects the strands with their complements by catalyzing the phosphodiester bonds with the 3' hydroxyl group and the 5' phosphate.

RNA
RNA (ribonucleic acid) is a single stranded nucleotide chain, not a double helix. While it does not share the same structure as DNA, it has many similar properties. RNA consists of a ribose sugar and hydroxyl group, as opposed to deoxyribose. RNA also consists of Adenine, Guanine and Cytosine, but Thymine is replaced with Uracil.

Types
There are three major types of RNA. While there are many other minor types, these three are heavily involved in translation.
 * Messenger RNA (mRNA): Encodes the sequence of amino acids that becomes a protein.
 * Transfer RNA (tRNA): Transports amino acids to ribosomes during translation. It contains about 80 RNA nucleotides, with an amino acid attached to the 3' end and an a complimentary anticodon attached to the 5' end.
 * Ribosomal RNA (rRNA): Along with ribosomal proteins, rRNA makes up the ribosome which is the organelle that translates mRNA into proteins.

Transcription
Transcription is the process of transcribing DNA into mRNA so that it can be translated into proteins. It is also the first major step of gene expression. Transcription produces a complimentary sequence to the DNA; A bonds with T in DNA, U bonds with A, G bonds with C and C bonds with G. For example:

DNA: GCACGTGTAGCATAGTACTAG mRNA: CGUGCACAUCGUAUCAUGAUC

Transcription occurs in the nucleus during the G1 and G2 phases of the cell cycle. In eukaryotes, it occurs in three distinct stages.

Initiation

 * 1) Activator proteins bind to distal control elements that are located before the DNA sequence known as a promoter. Promoters are located near the start sites of genes, and allow various proteins and enzymes (such as RNA polymerase II) to form an initiation complex that begins transcription.
 * 2) Proteins called transcription factors bind to a specific DNA sequence known as a promoter. At this point in the process, the DNA is still double stranded. RNA polymerase binds to the promoter region shortly after the transcription factors.
 * 3) RNA polymerase unwinds approximately 14 base pairs to form an "open complex" that becomes the transcription bubble. As the RNA polymerase begins creating RNA, it enters the RNA exit channel and leaves behind the initial transcription factors.

Elongation

 * 1) RNA polymerase begins unwinding the double helix and exposes 10-20 nucleotides for transcription at a time. To do this, RNA polymerase uses free-floating RNA nucleotides in the nucleoplasm.
 * 2) RNA polymerase travels from the 3' → 5' direction on the template strand of DNA, producing a mRNA strand in the 5' → 3' direction. This process produces an RNA copy of the 5' → 3' strand of DNA.
 * 3) RNA transcription occurs very quickly, and can involve multiple RNA polymerase working on a single gene. The typical rate of elongation is 10-100 nucleotides/sec.
 * 4) Elongation also involves a proofreading mechanism that can replace incorrect nucleotides. Transcription pauses, allowing RNA editing factors to bind to the new strand of mRNA and edit base order.

Termination

 * 1) The RNA codes for the polyadenylantion (AAUAAA), and the proteins that have been associated with the RNA polymerase stop moving.
 * 2) RNA polymerase continues moving, adding hundreds of adenine nucleotides to the end of the mRNA strand. Spare RNA created like this may be used by enzymes.
 * 3) This termination factor releases the newly created mRNA, which leaves the nucleus and travels to the ribosome where it is translated into a protein.

Interpreting Genetic Code
A sequence of three mRNA nucleotides is called a codon. Each of these codons corresponds with a complimentary anticodon attached to a strand of tRNA. Different tRNA molecules are attached to different amino acids, meaning that each codon corresponds with one amino acid. Since there are only four different RNA nucleotides, there are 64 possible codons. However, there are only 20 standard amino acids. This means that multiple codons can code for the same amino acid.

A chain of amino acids is called a protein. They are responsible for most biological functions in the body such as DNA replication, transcription, transporting molecules, and regulation of gene expression. Proteins are very complex macromolecules and have four different levels of structure. The amino acid sequence created in translation is known as the primary structure.

It is possible to interpret a DNA sequence into an amino acid sequence by using a chart like the one shown below.
 * Find the RNA nucleotides that would pair with the DNA nucleotides.
 * DNA: TAC AGG TAG CTA GTT ATT
 * RNA: AUG UCC AUC GAU CAA UAA
 * Follow the sequence of nucleotides on the chart from the inside out. For example, the RNA sequence AUG is found at the beginning of every protein and codes for Methionine. In the center of the circle, start with the A quadrant, then follow the U quadrant and then the G quadrant.
 * RNA: AUG UCC AUC GAU CAA UAA
 * Amino Acids: Methionine Serine Isoleucine Aspartic Acid Glutamine Stop

Translation
Translation is the process of translating the mRNA created during transcription into a protein. These proteins are responsible for different genetic traits such as hair/eye color, blood type, or hereditary conditions such as color blindness. It takes place in the ribosome, an organelle with three chambers and two subunits that consists of rRNA and other proteins. The three chambers are the A site (Aminoacyl-tRNA binding site), the P site (Peptidyl-tRNA binding site) and the E site (Exit site). All of these chambers are located in the large subunit. Like transcription, it occurs in three steps.

Initiation

 * 1) The small subunit attaches to the mRNA, holding it in place throughout translation.
 * 2) The Methionine tRNA bonds to the start codon AUG.
 * 3) The large subunit arrives and completes the translation initiation complex.

Elongation

 * 1) Amino acids are brought to the ribosome by tRNA molecules and are added to the polypeptide chain one by one.
 * 2) The anticodon on a tRNA molecule binds to the mRNA codon at the A site.
 * 3) An rRNA molecule in the large subunit catalyzes the formation of a peptide bond between the amino acid on the tRNA and the polypeptide chain.
 * 4) The ribosome moves the mRNA to from the P site to the E site, where the tRNA is released.

Termination

 * 1) The stop codon on the mRNA reaches the A site.
 * 2) Release factors bind to the stop codon at the A site.
 * 3) A water molecule is added to the end of the polypeptide instead of an amino acid, and hydrolysis releases the chain so it can be folded into its final structure.

Single-Factor Crosses (Monohybrid)


The images to the right are examples of Punnett squares, named after the geneticist Reginald C. Punnett. Punnett squares show the cross between alleles and the genotype of the resulting offspring. Since both of the Punnet squares in the diagram only cross one trait (one pair of alleles), it is called a monohybrid or single-factor cross. Likewise, when two traits (two pairs of alleles) are crossed, it is called a dihybrid or two-factor cross.

The first Punnett square shows a cross between two heterozygous plants. The second Punnett square shows a cross between a homozygous tall plant and a homozygous short plant. The letters inside the boxes represent the genotype of each offspring. For example, in the first square, the genotypes of the offspring will be TT, Tt, and tt (2 of the 4 offspring will have the same genotype-Tt).

It is helpful to memorize the genotypic and phenotypic ratios of a heterozygous monohybrid cross. If two heterozygotes are crossed (like the first Punnet Square in the image to the right) then the genotypic ratio will always be:

1 D/D: 2 H: 1 R/R

and the phenotypic ratio will be:

3 D: 1 R

where D=homozygous dominant, R=homozygous recessive, and H=heterozygous.

Memorizing other simple crosses (such as a single-factor homozygous dominant x homozygous recessive cross) is useful and saves time on tests. Here are some simple monohybrid crosses with their respective genotypic and phenotypic ratios.

AA x aa (Homozygous dominant x Homozygous recessive)

Genotypic ratio: 0 D/D: 4 H: 0 R/R

Phenotypic ratio: 4 D: 0 R

AA x Aa (Homozygous dominant x Heterozygous)

Genotypic ratio: 2 D/D: 2 H: 0 R/R

Phenotypic ratio: 4 D: 0 R

Aa x aa (Heterozygous x homozygous recessive)

Genotypic ratio: 0 D/D: 2 H: 2 R/R

Phenotypic ratio: 2 D: 2 R

Some important Punnett Square terms are defined below. On tests, be extra careful when you spot these terms as they are easily confused with each other.


 * Genotype: The different combinations of the alleles.
 * Phenotype: The physical appearance of the offspring.


 * Genotypic ratio: The ratio of the combination of alleles.
 * Phenotypic ratio: The ratio of the physical appearance.

Two-Factor Crosses (Dihybrid)
Two factor crosses, or dihybrid crosses, are similar to single-factor crosses except that in a two-factor cross, two traits are crossed rather than one trait in a single-factor cross. An example of a two-factor cross is pictured to the left.



Here, two heterozygotes are crossed (RrYy x RrYy). The "R" allele represents the shape of the seed and the "Y" allele represents the color. It is important to note the genotypic and phenotypic ratios for a heterozygous dihybrid cross. Regardless of the alleles, if two dihybrid heterzygotes are crossed, then the resulting phenotypic ratio will be:

9 D/D: 3 D/R: 3 R/D: 1 R/R (D = dominant, R = recessive).

and the genotypic ratio will be:

1 D/D: 2 D/H: 1 D/R: 4 H/H: 4 H/D: 1 R/D: 2 R/H: 1 R/R (H = heterozygous).

So, the phenotypic ratio for the pictured dihybrid cross is:

9 round/yellow:3 round/green: 3 wrinkled/yellow: 1 wrinkled/green.

Three-Factor Crosses (Trihybrid)


Like single- and double-factor crosses, three-factor crosses (trihybrid) show three different traits that are crossed (see the image to the right for an example). Trihybrid crosses are rarely seen on tests, so don't spend too much time practicing them until the later stages of competition.

Incomplete dominance
In some unusual cases such as 4 o'clock flowers, gene pairs for a given trait fail to establish dominance and the heterozygous condition is expressed as an intermediate between the two alleles. Often, to draw attention to this situation, the letter 'I' is used to designate the gene allele.

Example: In 4 o'clock flowers, the genotype RR (homozygous dominant) appears red, rr (homozygous recessive)appears white, and Rr (heterozygous)appears pink. In all cases of incomplete dominance, the number of genotypes equals the number of phenotypes.

Epistasis
Epistasis is where one set of genes stops or inhibits the action of another genes. Epistasis genes can either be recessive or dominant. The gene for no pigment (p) in the skin(albinism) is recessive to normal pigmentation(P). For any pigment to appear at all, at least one gene for enzyme S must also be present. That's like even if there is a pigment, but enzyme S is not present, the person is albino. PpSs? is normal, PPss? is albino, ppSS is albino, and so on. To not be albino, there needs to be at least one P and one S.

Sex-linked traits
Sex-linked traits are features that are associated with the genes on the sex chromosomes, usually X. Examples of those are recessive genes for color-blindness and hemophilia.

Sex-influenced traits
Sex influenced traits are traits that show up more in one sex than they do in the other as a definite phenotype. Usually influenced more by hormones in the male or female.

Multiple genes
Most phenotypic features are controlled by more than one set of non-allelic genes acting on them, such as height, skin color, intelligence, and hair and eye color. Usually this type of problem is seen as a typical two or three, etc factor cross with the more dominants, the more expression of the trait in question.

Multiple alleles
There may be more than the usual two alleles for any given gene. Especially, this appears in fur or pelt conditions of domestic animals. The problem usually uses 'I' (for incomplete dominance) and some prearranged superscript. The most common example found on tests is the ABO blood type system found in humans.

Lethal alleles
While lethal alleles do not affect the way you set up your Punnett square, they can appear to alter Mendelian ratios. A lethal genotype is one that causes death before the individual can reproduce and pass their genes on to the next generation. As such, they remove an expected progeny class after a specific cross. For example, in Mexican hairless dogs, the genotype hh means that te dog is hairy, Hh means that the dog is hairless, but HH means that they die as embryos--thus the term "lethal".

Genetic Disorders
Genetic disorders are inherited medical conditions caused by abnormalities in the DNA. There are a variety of types of genetic disorders, and some are rarer than others. They are typically caused by mutations in specific genes, deletion of genes, or a person having an additional chromosome. While these genes can be known as disease-causing genes, the abnormality of a gene is the cause of the disorder.

One of the most common genetic disorders is known as trisomy 21, or Down Syndrome. An individual with this disorder has a third copy of chromosome 21. Cystic fibrosis is also a genetic disorder, caused by mutation in a protein known as CFTR. Even color blindness is a genetic disorder, caused by a mutation on the X chromosome.

Karyotypes
A karyotype is a chart that shows each chromosome. Each karyotype displays 23 pairs of chromosomes, including the X/Y chromosomes. Every pair is assigned a number (except for the sex chromosomes; they are always referred to as the X and Y chromosomes). Some genetic disorders can be detected by analyzing the number of chromosomes and/or the sex chromosomes. The gender of the individual can also be deduced from looking at the sex chromosomes. If there is an X and a Y, the individual is a male. A female has two X chromosomes and no Y chromosome.

A karyotype is created by stopping cells in cell division and staining the chromosomes, then observing them under a light microscope.

Karyotypes can be used to diagnose genetic diseases. For example, a karyotype can reveal a third chromosome 21, resulting in Down syndrome. It can also reveal Turner syndrome (45, X), a disorder that results in females with one X chromosome, and Klinefelter's syndrome (47, XXY), in which a man has two X chromosomes and one Y chromosome.

Sex determination
In humans, the male and female share 22 of the 23 pairs of chromosomes in each body cell. The 23rd pair is known as the sex chromosomes because it determines the sex of the individual. In the male, the sex chromosome consists of an X and a Y chromosome(XY) while the pair in females consists of two X chromosomes(XX). The male is the one who determines the sex of the child and the female gives an X to all eggs while the male randomly produces about 50% X sperm and 50% Y sperm.

In rare cases, through nondisjunction, a person will have three sex chromosomes. If they have three X (XXX) chromosomes, they are female. If they have even one Y chromosome (XXY), they are male. Although they will show more feminine qualities, any person who has a Y chromosome is considered a male. Other types of sex chromosome polysomy, as well as one monosomy (X), have been known to occur, though much more rarely.

Resources
Molecular Biology of the Cell notes