Genetics: Pedigree Analysis and Terminology

• Genetics is the study of genes, which carry information passed from one generation to the next

Pedigree Analysis

• A pedigree chart diagrams the inheritance of a trait or health condition through generations of a family
• Phenylketonurics are people who suffer from Phenylketonuria (PKU), making it difficult to metabolize phenylalanine

Genetic Terminology

• Allele: A variant form of a gene (dominant or recessive)
  • An allele is dominant when it effectively overrules the other (recessive) allele
• Dominant Allele: An allele that is expressed if present in the genotype
• Recessive Allele: An allele whose expression is masked by a dominant allele
• Genotype: An individual's allele combination for a particular gene, represented by letters
• Phenotype: An observable characteristic or physical appearance
• Homozygous: Possessing identical alleles of one gene, either:
  • BB (Homozygous Dominant) or bb (Homozygous Recessive)
• Heterozygous: Possessing different alleles of one gene, represented as Bb
  • The dominant allele will be expressed
• True-Breeding: Homozygous individuals that self-fertilize yield offspring identical to themselves for a given trait
• Hybrid: Heterozygous individuals that self-fertilize yield offspring with different traits

Punnett Square

• Monohybrid Cross: Crosses involving only one trait

Dihybrid Cross

• Dihybrid Cross: Crosses involving two traits

Pedigree Charts

• Standard symbols are utilized

Pedigree Chart Key

• Male (square) vs. Female (circle)
• Affected (shaded) vs. Unaffected (unshaded) individuals
• Marriage/mating line (connecting mates) vs. Sibship line (connecting siblings)
• Fraternal twins: one birthline branches out into the individual twins
  • Identical twins: same as fraternal twins with a horizontal bar connecting the branches
• Generations are labeled with Roman numerals, individuals in the same generation are numbered from left to right with Hindu-Arabic numerals
• Proband: Indicated by an arrow

Pedigree Construction Practice

• Pedigree charts can be constructed to represent family relationships and inheritance patterns of traits or conditions

Law of Segregation

• F1 Parents contained two separate copies of each hereditary factor, either dominant or recessive
• Factors separate when gametes are formed, each gamete carries only one copy of each factor
• Random fusion of all possible gametes occurs during fertilization

Law of Independent Assortment

• Each pair of factors segregates (assorts) independently of other pairs
• All possible combinations of factors occur in the gametes

Sex-Linkage and Recombination

• Sex-linked Trait: The gene (or pair) determining a character (e.g., hemophilia) is located on the sex chromosomes
• X-linked Trait: A sex-linked trait where the gene or allele for the trait is found on the X chromosome
• Y-linked Trait: A sex-linked trait where the gene or allele for the trait is found on the Y chromosome
• Sex-influenced Trait: Any trait in a diploid organism whose expression is affected by an individual's biological sex
  • Occurs at a higher frequency in one sex versus the other
• Sex-limited Trait: Any trait in a diploid organism whose expression is limited to just one biological sex

Sex-Linked Traits

• The gene determining a character is located on the sex chromosomes
  • Females have two X chromosomes, while males have one X and one Y chromosome
• In X-linked traits, the allele on the X chromosome is shown as a letter attached to the X chromosome

Sex-Influenced Traits

• Autosomal traits appear in both sexes but are expressed to a different degree in each
  • Acts as dominant in one sex and recessive in the other

Sex-Limited Traits

• Genes occur in both sexes (autosomes) but are normally expressed only in the gender having the appropriate hormonal determinant
  • Does not occur in all members of that sex
• Hormonal or physiological differences between sexes may limit the expression of some genes to one biological sex only

Modifications to Mendel's Classic Ratios (Non-Mendelian Genetics)

• Co-dominance: A type of inheritance in which two versions (alleles) of the same gene are expressed separately to yield different traits in an individual
• Incomplete Dominance: Form of gene interaction where both alleles of a gene at a locus are partially expressed
  • Results in an intermediate or different phenotype or a blending of alleles
• Multiple Alleles: When there are more than two types of alleles for a given locus or trait
  • Results in more than two kinds of phenotypes that may be expressed for that trait

Mendelian vs. Non-Mendelian Genetics

• Mendelian inheritance is the way genes and traits are passed from parents to offspring through dominant and recessive alleles
• Non-Mendelian inheritance: the pattern where two alleles are neither dominant nor recessive

Molecular Structure of DNA, RNA, and Proteins

• Polymer: A long-chain molecule made up of a repeated pattern of monomers

DNA

• Full name is Deoxyribonucleic acid
• Form: Double-stranded
• Sugar: Deoxyribose
• Nucleotide Bases: Adenine (A), Thymine (T), Cytosine (C), and Guanine (G)

RNA

• Full name is Ribonucleic acid
• Form: Generally single-stranded
• Sugar: Ribose
• Nucleotide Bases: Adenine (A), Uracil (U), Cytosine (C), and Guanine (G)

Functions of the Acids

• DNA stores RNA and protein-encoding information and transfers information to the next generation of cells
• RNA stores protein-encoding information, helps to make proteins, and catalyzes some reactions

Structure of Nucleic Acids

• Nucleotides made up of three components:
  • Nitrogenous base
  • Pentose (five-carbon) sugar
  • Phosphate group
• Two nucleotides are bonded by a phosphodiester bond, linking the phosphate group of one nucleotide and the sugar of another nucleotide
• DNA molecules form a double helix shape in an antiparallel orientation, with one pyrimidine and one purine

Base Pairings

• Two strands of DNA are linked by hydrogen bonds between paired bases
  • Pairing a purine with a pyrimidine results in a uniform diameter for the helical shape of DNA

Types of Proteins and Their Functions

• Enzymatic Proteins accelerate chemical reactions
  • Example: digestive enzymes catalyze the hydrolysis of bonds in molecules
• Defensive Proteins protect against diseases
  • Example: antibodies inactivate and help destroy viruses and bacteria
• Storage Proteins store amino acids
  • Example: Casein in milk is a major source of amino acids for baby mammals
• Transport Proteins transport substances
  • Example: Hemoglobin transports oxygen from the lungs to other parts of the body
• Hormonal Proteins coordinate an organism's activities
  • Example: Insulin, secreted by the pancreas, causes other tissues to take up glucose, regulating blood sugar concentration
• Receptor Proteins trigger responses to chemical stimuli
  • Example: Receptors in the membrane of a nerve cell detect signaling molecules released by other nerve cells
• Contractile and Motor Proteins are responsible for movement
  • Example: Actin and Myosin proteins contract of muscles.
• Structural Proteins support
  • Example: Keratin is the protein of hair and other skin appendages, Collagen and elastin proteins provide a fibrous framework in animal connective tissues

Amino Acids

• There are Twenty 20 different types

Protean Structure

• The structure of a protein is analogous to a shaped knitted yearn product

Levels of Protein Structure

• Primary Structure: The sequence of amino acids
• Secondary Structure: Proteins fold and align themselves into alpha-helix and beta-pleated sheets
• Tertiary Structure: The overall 3D arrangement of a polypeptide resulting from interactions between the side chains of the various amino acids
• Quaternary Structure: The overall protein structure that results from the aggregation of these subunits

The Central Dogma

• Genes along the DNA molecule can direct synthesis of RNA (mRNA or Messenger RNA)
• RNA molecules aid in the synthesis of polypeptides, forming proteins

DNA Replication (DNA -> DNA)

• DNA replication is the process by which more DNA is created
  • Results in two copies of DNA, one original and one new strand
• Semiconservative Replication: results in one of the two old strands of DNA is conserved, present in each daughter molecule
• DNA elongates from the 5' to 3' direction, where nucleotides add to the 3' carbon end of a strand
• Leading Strand (3' to 5'): Synthesized continuously (5' to 3')
• Lagging Strand (5' to 3'): Discontinuously chunked together

DNA Replication Enzymes

• Helicase (Unzipping Enzyme): Unzips or separates the two strands of DNA
• DNA Polymerase (The Builder): Replicates DNA molecules to build a new strand of DNA
• Primase (The Initializer): Makes the primer (starting point) of replication
• Ligase (The Gluer): Helps glue DNA fragments together

Replication Steps

• Helicase separates the strands
• Single-strand binding proteins (SSBP) prevent the unwound strands from rejoining
• Topoisomerase untwists the double helix so it lays flat
• Primase (Initializer) makes a short stretch of RNA on the DNA template to start the replication process
• DNA polymerase adds DNA nucleotides to the RNA primer and continues the process down the strand
• Leading (continuous) strand synthesizes continuously in a 5' to 3' direction
• Discontinuous synthesis of the lagging strand produces Okazaki fragments, which are stitched together later
• After RNA primer is replaced with DNA nucleotides, ligase seals the sugar-phosphate backbone, gluing everything up

Three Types of RNA

• mRNA (Messenger RNA): Carries the genetic information that specifies a protein
• tRNA (Transfer RNA): Carries amino acids to the ribosome, transferring amino acids to match the correct mRNA codon
• rRNA (Ribosomal RNA): Forms the ribosome where the site of protein synthesis occurs

DNA Transcription (DNA -> mRNA)

• DNA is copied into mRNA, and takes place in the nucleus
  • Cytosine (C) pairs with Guanine (G)
  • Uracil (U) pairs with Adenine (A)
• RNA polymerase binds to a region of a gene called the promoter
  • DNA unwinds exposing the nucleotides so the RNA polymerase can “read” and make a sequence of bases
• RNA Polymerase adds RNA nucleotides in a 5' to 3' direction
• RNA polymerase reaches the terminator gene signaling the release of the new mRNA strand and the removal of the enzyme to the DNA template

Processing RNA

• Addition of a 5' cap to the beginning of the RNA
• Addition of a poly-A tail to the end of the RNA
• Chopping out introns and pasting together the remaining, good sequences (Exons)

DNA Translation (mRNA-tRNA)

• The information carried in mRNA molecules is used to create proteins
• Takes place in the cytoplasm (ribosomes)
• Steps
  • Initiation: The small ribosomal subunit attaches to the mRNA in the vicinity of the start codon
  • tRNA carries the amino acid methionine, which pairs with this mRNA codon
  • The large ribosomal subunit joins the small subunit
  • Elongation: During the elongation cycle, the polypeptide chain increases in length (one amino acid at a time)
  • Termination: Stop codon appears at the A site.

Genetic Engineering -> Biotechnology

• Classical breeding uses interbreeding (crossing) of closely or distantly related individuals to make new varieties or lines with desirable properties
• Selective breeding, a.k.a. artificial selection, is a process used by humans to develop new organisms with desirable traits or characteristics
  • Genetic engineering involves molecular techniques to modify the traits of a target organism
  • Biotechnology manipulates organisms or their components to make useful products
• Recombinant DNA Technology: Recombinant DNA is a molecule containing DNA from two different sources

Generating Recombinant DNA

• A researcher needs a vector such as a plasmid
• Cut the plasmid using restriction enzymes
• Seal the foreign piece of DNA into the plasmid using DNA ligase
• Return the plasmid to the bacterial cell
• Bacterial cell reproduces, thus replicating the desirable gene (gene cloning)
• Researchers isolate copies of a cloned gene from bacteria for many purposes

Plasmid Insertion

• Biolistics: gene gun use a gene gun to fire small metal particles coated with DNA into plant tissues
• Heat shock treatment Heats bacteria to open their cell membrane pore to allow Plasmid DNA insertion
• Electroporation triggers expansion of the cell membrane with an electric shock

Screening

• Separate DNA fragments using technology to asses their size
• Gel electrophoresis (DNA fingerprinting) investigates crime scenes and analyzes genes with an illness
• Use the polymerase chain reaction a technique the amplifies predicted products the determine whether the gene is confirmed in the sample material

Genetically Modified Organisms

• Bacteria (promote plant health & degrade material)
• Improved Crop quality (Flavr Save Tomato)
• Enhanced plants (BT Corns)
• Changed animals