Genetics - Comprehensive Note

Ocular Albinism - X-Linked Trait

• Ocular albinism is an X-linked recessive trait, meaning it's located on the X chromosome.
• When determining probabilities, it's crucial to track the X chromosome.
• Females have two X chromosomes (XX), while males have one X and one Y chromosome (XY).
• If a woman has ocular albinism (X-linked recessive), her genotype must be X^aX^a, where 'a' represents the recessive allele.
• If a man does not have ocular albinism, his genotype is X^AY, where 'A' represents the dominant allele.
• When both parents genotype is given, the probability of their child having ocular albinism can be calculated using a Punnett square.
• If only sons are considered, the probability of having ocular albinism is 100%; for all children, it's 50%.

Dominance

• Complete Dominance: The dominant allele determines the phenotype, regardless of the other allele present.
• Incomplete Dominance: The heterozygote phenotype is an intermediate between the two homozygous phenotypes.
  • Example: Crossing a white flower with a red flower results in pink flowers.
• Codominance: Both alleles contribute equally and are distinctly expressed in the phenotype.
  • It is possible to detect both phenotypes.

ABO Blood Type - Codominance Example

• O allele is recessive to both A and B alleles.
• A and B alleles are codominant when present together.
• Phenotypes and Genotypes:
  • Type A: Genotype can be AA or AO.
  • Type B: Genotype can be BB or BO.
  • Type AB: Genotype is AB (codominance, both A and B are expressed).
  • Type O: Genotype is OO (lack of A and B alleles/expression).
• Recessive alleles (like O) often represent a lack of a specific coding product.
• AB blood type individuals cannot have children with type O blood.
• Besides ABO, there are other blood type categories such as the Rh factor (positive or negative).
  • The ABO and Rh factor are important for blood transfusions and can trigger immune responses if mismatched.
• Type O blood is the universal donor because it lacks antigenic molecules that stimulate an immune response.
• Type AB positive blood is the universal recipient and can receive blood from all types.

Blood Type Practice Question

• Representing blood type with 'I' (immunoglobulin) can indicate the recessive nature of the O allele (e.g., I^AI^O for type A).
• Punnett square analysis for parents with specific blood types allows predicting the probability of offspring blood types.

Pleiotropy

• Describes when one gene has many phenotypic effects.
• Genetic diseases, like cystic fibrosis, are examples of pleiotropic conditions.
• Cystic Fibrosis:
  • Mutation in the gene responsible for producing chloride ion channels in respiratory and digestive tracts.
  • Leads to thick, sticky mucus accumulation, causing increased lung infections and digestive issues.
• Sickle cell anemia and albinism are other examples of pleiotropic traits.

Polygenic Traits

• Multiple genes contribute to a single phenotype.
• Eye color is a polygenic trait influenced by at least six different genes.
• Polygenic traits show continuous variation, with phenotypes falling along a continuum rather than discrete categories.
• Examples: skin color, height, and beak depth in birds are polygenic traits.
• The majority of the population tends to fall near the average or intermediate phenotype for polygenic traits.

Epistasis

• One gene affects or modifies the expression of another gene.
• The genotype at one locus determines whether a gene at another locus is expressed.
• Example: Coat color in mammals.
  • One gene determines the coat color (e.g., black or brown).
  • Another gene determines whether the pigment is deposited in the fur.
  • If the pigment deposition gene is recessive, the animal will be white, regardless of the coat color genes.
• Albinism can also be an example of epistasis where a gene prevents pigment deposition in skin, eyes and hair.

Multifactorial Inheritance

• Environment influences gene expression.
• Examples:
  • Allergies: Require exposure to an allergen to trigger a response.
  • Skin color: Influenced by sunlight exposure.
  • Weight: Underpinned by genetics but also affected by diet and gut microbiome.
  • Phenylketonuria (PKU): A genetic condition where lacking an enzyme to break down phenylalanine leads to mental disabilities if the diet isn't modified.
• Arctic fox coat color change according to the seasons and the pH affecting hydrangeas.

Nucleic Acids and DNA Replication

• Nucleic acids are biological macromolecules. The two types are DNA and RNA.
• DNA stands for deoxyribonucleic acid. RNA stands for ribonucleic acid.
• The monomer of a nucleic acid is a nucleotide.

Nucleotide Structure

• Three Parts:
  • A five-carbon sugar (deoxyribose in DNA, ribose in RNA).
  • A nitrogenous base (adenine, thymine, cytosine, guanine in DNA; adenine, uracil, cytosine, guanine in RNA).
  • A phosphate group.
  • Sugars are numbered with primes, for example carbons are named using 1', 2', 3', 4' or 5'.
• Nucleotides have a five prime end (5') because of the phosphate group and a three prime end (3') due to a hydroxyl group. All sugars have an orientation and run five prime to three prime.

Properties of DNA

• DNA is double-stranded.
• Erwin Chargaff's Rules:
  • The amount of cytosine (C) is roughly equal to the amount of guanine (G).
  • The amount of adenine (A) is roughly equal to the amount of thymine (T).
  • The relative quantities of these bases differ between organisms.
• Base Pairing:
  • A pairs with T.
  • G pairs with C.
• Complementary Sequencing: Knowing the sequence of bases on one strand allows prediction of the sequence on the other strand due to the base pairing rules.
• Strands run from opposite directions and are therefore antiparallel
• Bases are held together by hydrogen bonds
• The percentage of each base can be determined using base pairing relations described above

DNA Replication

• During cell division, DNA is replicated using both strands of the existing DNA molecule as a template to build new strands from.
• The model used is semi conservative meaning the molecule splits apart during DNA replication, and each existing strand serves as a template so that when we have a DNA copy, each copy of the strand actually exists from one original strand and one new.

Starting Point of DNA Replication

• A sequence on the chromosome that serves as that starting point is going to track the machinery to start synthesizing the molecule.
• Points where copying starts called origin of replication
• DNA replication is bidirectional.
• Replication forks are points where strands are dividing.
  • Prokaryotes have circular chromosomes. Therefore, replication happens at one origin. Eukaryotes have multiple origins of replication.

Molecular Machinery for DNA Replication

• Helicase: Unzips the helix by breaking hydrogen bonds between nitrogenous bases.
• DNA topoisomerase: Prevents separation of the parent strands from causing supercoiling and runs ahead of our replication fork.
• single stranded binding proteins: clamp on to the newly revealed parent strand until the enzyme that's gonna use as a template to make a new strand DNA can come back.
• DNA polymerase: Runs along the DNA template to synthesize DNA in a 5' to 3' direction, always adding nucleotides to the 3' end.
• Primase: Lays a karma or anchor for DNA polymerase to hang on to. This is a RNA called a primer. Polymerase needs this in order to start synthesyzing.
• DNA polymerase can only synthesize DNA in a 5' to 3' direction. DNA polymerase has to synthesize away from the replication fork
• Leading Strands are strands where the fork is synthesized continuously. A lagging strand consist of bits and pieces because the strands are synthesized at any point where that template is exposed.
• Little bits of DNA are synthesized at a time as the template is revealed = Okazaki fragments
• Eventually all the primers are removes and a different DNA polymerase will replace it with DNA nucleotides.

Eukaryotic DNA Replication

• Ends of chromosomes can't get replicated because there is not a three prime end.
• Over time, chromosomes get shorter.
• Eukaryotic chromosomes have telomeres at the end of the chromosome. They're short bits of repeating DNA, but they're just there so your cell can delete them without ruining your coding DNA.
• Your cell can delete parts without affecting the coding part
• Each time the cell divides, telomeres get shorter.
• Telomeres can elongate germ cells, where as cancer cells can also divide without shortening them too much.