DNA

• DNA helps with the following:
  • Forensic science
  • Paternal testing
  • DNA profiling
  • Study human migration patterns
  • Development of vaccines
  • Identification of biological remains
• DNA stands for Deoxyribonucleic Acid and it is stored in the nucleus of the cell
• It contains all the instructions for the function of the cell
• DNA coils tightly to form a chromosome
  • This ensures no DNA is lost during cell division
• Humans have 46 chromosomes in every cell
• A gene is a segment of DNA that codes for a particular trait
  • E.g. ability to curl your tongue, hair colour, eye colour
• Multiple genes can be found on a single chromosome (chromosome 1 has over 2000 genes on it!)
• Nucleotide: Phosphate - Sugar - Base
• The backbone of DNA = Phosphate and Sugar

DNA Replication

• Helicase ==(Step 1)==
  • The ‘unzipping’ enzyme
  • Comes and unwinds the DNA
  • Topoisomerase prevents DNA from supercoiling (stops overwinding of DNA)
• Primase ==(Step 2)==
  • Primase comes in and makes RNA primers on both strands
  • This is an important step so DNA polymerase knows where to start
• Complementary Strands
  • Complementary strands are joined by hydrogen bonds and move in antiparallel directions
  • One strand goes 5’ to 3’ and the other goes 3’ to 5’ (based on the labelling of the sugar molecules Carbons)
• DNA Polymerase ==(Step 3)==
  • DNA polymerase builds the new strand in the 3’ to 5’ direction (using the old template strand as a base)
  • It also has a proofreading ability, so it rarely makes mistakes
  • The leading strand is complete, but the lagging strand is built in the wrong direction and has lots of gaps in it (known as Okazaki Fragments)
• Ligase ==(Step 4)==
  • Ligase comes along and fills in the gaps between each of the Okazaki Fragments
• End Product
  • Two identical double-helix DNA molecules
  • This is semi-conservative because each of the two new copies contains one of the original strands of DNA

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Cell Division

• ==Cell division: the process by which one cell (parent cell) divides into two new identical daughter cells==
  • This helps them grow and produce more cells
  • It also helps repair damaged tissues
• Before cell division occurs, cell replicates all of its DNA so each daughter cell gets a complete copy of genetic information from the parent cell
• Asexual Reproduction
  • Many organisms, especially unicellular organisms reproduce by cell division e.g. bacteria
• Somatic (body) cells
  • All body cells in an organism have the same kind and number of chromosomes
  • We have 22 pairs of body chromosomes and 1 pair of sex chromosomes - a total of 23 chromosomes in the human body
• Interphase
  • Period of cell growth and development
  • DNA replication occurs during this phase
  • Cells spend most of their time in this part of the cycle, where it is able to carry out normal cell activities

Mitosis

• Prophase
  • Chromosomes coil up
  • Nuclear envelope disappears
  • Spindle fibers form
• Metaphase
  • Chromosomes line up in the middle of the cell
  • Spindle fibers connect to chromosomes
• Anaphase
  • Chromosome copies divide
  • Spindle fibers pull chromosomes to opposite poles
• Telophase
  • Chromosomes uncoil
  • Nuclear envelopes form
  • 2 new nuclei are formed
  • Spindle fibers disappear

• Cytokinesis
  • Division of the rest of the cellar after the nucleus divides
  • Cell then returns to interphase to continue to grow and perform cell activities
• DNA controls all cell activities including cell division
  • If the DNA is damaged/mutated, then the cell loses their ability to control cell division
  • This causes super-dividing masses called tumors
  • Benign = Not cancerous
  • Malignant = Cancerous

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Mutations

• What is a mutation?
  • When DNA replicates itself, there are sometimes errors that aren’t detected and fixed (due to mutagens or chance)
  • Changes in the letters of the code also change the meaning of the code, which can have severe effects.
  • Too much or too little proteins could be produced.
  • Proteins help control and regulate iron levels leading to too much iron in the blood which can damage organs.
• Types of mutation
  • Substitution
  • Letters of code are changed from their original intended sequence
  • Insertion
  • Extra letters of code are inserted into the original intended sequence
  • Deletion
  • Letters of code are deleted from the original intended sequence
• What is a mutagen?
  • A factor that triggers mutations
  • Over-exposure to X-Rays, UV rays, or chemicals in pesticides are all mutagens.
• Are mutations inherited?
  • If the sperm and ovum carries a DNA abnormality then the child could be affected with a genetic disorder
  • Examples of genetic mutations include:
  • Red-green colour blindness
  • Haemophilia
  • Cystic Fibrosis
• Mutations: Pros & Cons
  • Not all mutations are harmful, in fact, some species actually rely on mutations in order to survive
  • Insects that have slight variations or mutations to their genetic code may be resistant to pesticides, and these are the ones who survive while the non-resistant ones die out.
  • Sickle Cell mutation occurs when an Adenine is replaced by a Thymine in the haemoglobin code
  • If a child inherits the trait from one parent, it can be beneficial, as the child will have no/mild symptoms but is resistant to malaria
  • Two copies, one from each parent lead to misshapen red blood cells that cause pain and block vessels
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Inheritance

• Mendel
  • Our understanding of the patterns of inheritance of genetic disorders and other characteristics involving peas
  • Mendel carried out experiments on peas to determine how individual traits are inherited
• Why did he use peas?
  • Peas grow quickly and therefore many generations can be grown in a relatively short time period
  • He used a large number of pea plants to complete his experiments
  • He found that each parent passed on half of its factors to each offspring and that certain factors were dominant over others
• Alleles
  • Gene = proportion of DNA that determines a certain trait
  • Alleles: different versions of the same gene
  • Individuals inherit two alleles from their parents: either dominant or recessive alleles
• Dominant or Recessive
  • Dominant allele: the allele that is expressed over the recessive allele
  • Represented by a capital letter (e.g. brown eyes are represented by ‘B’)
  • Recessive alleles: the allele that is only expressed if BOTH alleles inherited are recessive
  • Represented by a lowercase letter (e.g. blue eyes are represented by ‘b’)
  • In rare cases, both the recessive and dominant allele can be expressed and produce a blending effect (e.g. red and white carnations can produce pink carnations)
  • Represented with upper and lowercase letters (Rr)
• Homozygous and Heterozygous
  • Let’s assume R = round pea shape (dominant trait) and r = oval pea shape (recessive trait)
  • Homozygous
  • Two copies of the same allele
  • EX: RR, rr
  • Heterozygous
  • Two different copies of an allele inherited from each parent
  • One dominant and one recessive
  • EX: Rr
• Genotype and Phenotype
  • Genotype: Unique sequence of DNA
  • Phenotype: The expression of the genotype (i.e. how the organism looks)

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Sex-Linked Traits

• Requirements of Test Crosses
  • Large numbers of offspring are needed to produce reliable data
  • Now we have genetic screening and genome mapping, test crosses are less commonly used
  • The Human Genome Project (2003) identified all the genes in human DNA and has allowed researchers to develop genetic tests to diagnose diseases
• Sex-Linkage
  • When a gene controlling the expression of a trait is located on a sex chromosome
  • e.g. X or Y
  • The Y chromosome is much shorter than the X and contains fewer genes
  • The X chromosome is longer and contains genes not present on the Y chromosome
  • Therefore, sex-linked conditions are usually X-linked
• Sex-Linked Patterns
  • Sex-linked traits tend to affect males more than females because they only have one X chromosome and cannot mask the trait with a second X chromosome
  • Females have two X chromosomes and therefore can carry two different alleles on their X chromosome
  • This can be heterozygous or homozygous
  • But remember the dominant gene is always expressed
• Rules for Sex Linkage
  • Only females can be carriers (heterozygous) for a recessive disease, males cannot be carriers because they are hemizygous and only have one X chromosome
  • Females cannot inherit an X-linked recessive condition from an unaffected father (there is only one X chromosome, so this is the dominant one)
• Writing Conventions: Sex Linkage
  • We write the allele as a superscript to the sex chromosome (X)
  • E.g.: Haemophilia: X^H = unaffected ; X^h = affected

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Pedigrees

• A pedigree is a type of diagram used to represent the individuals in a family and track the inheritance of a particular trait in that family

  

• Symbols:

  • Unshaded square = Normal male
  • Shaded square = Affected male
  • Half-shaded square = Carrier male
  • Line between a square and a circle = Parents/Married
  • Line joined ABOVE a square and a circle = Siblings
  • Unshaded circle = Normal female
  • Shaded circle = Affected female
  • Half-shaded circle = Carrier female
  • Oldest offspring on the left - offspring must be in birth order
  • A triangular line joining offspring = Identical twins
  • Line looking like ^ joining offspring = Non-identical twins

• Autosomal Dominant

  • If both parents are affected and the offspring is unaffected, the trait must be dominant (parents must be heterozygous)
  • All affected individuals must have at least one affected parent
  • If both parents are unaffected, all offspring must be unaffected (homozygous recessive)

• Autosomal Recessive

  • If both parents are unaffected and the offspring are affected, the trait must be recessive (both parents are heterozygous carriers)
  • If both parents show a trait, then all offspring will show the trait (homozygous recessive)

• X-linked Dominant

  • If a male shows a trait, all daughters as well as his mother must show the trait.
  • Unaffected mothers cannot have affected sons
  • Tends to be more common in females

• X-linked Recessive

  • If a female shows a trait, all the sons and their father must also have the trait
  • Unaffected mothers can have affected sons if she is a carrier (heterozygous)
  • X-linked recessive tend to be more common in males

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