The likelihood that an event will occur. # on dieprobability 11/ The probability of an event = # of chance of event total possible events The probabilities of all the possible events add up to 1. No chance of event probability = 0 (e.g. chance of rolling 8 on a six-sided die) Event always occurs probability = 1 (chance of rolling 1,2,3,4,5,or 6 on a six-sided die)

The product rule sates: The probability of independent events is calculated by multiplying the probability of each event. In two rolls of a die, the chance of rolling the number 3 twice: Probability of rolling 3 with the first die = 1/6 Probability of rolling 3 with the second die = 1/6 Probability of rolling 3 twice = 1/6 x 1/6 or 1/36

The probability of dependent events is calculated by adding the probability of each event. In one roll of a die, what is the probability of rolling either the number 5 or an even number? Probability of rolling 5 or an even number = 1/6 + 3/6 or 4/6 Probability of rolling the number 5 = 1/6 Probability of rolling an even number = 3/6

What is the chance of an offspring having the homozygous recessive genotype when both parents are doubly heterozygous?

Parents are heterozygous for a trait, R. What is the chance that their child is carries at least one dominant R allele? Probability of child carrying RR = 1/4 Probability of child carrying Rr = 1/2 Probability of child carrying R_ = 1/4 + 1/2 = 3/4

 Hemophilia was one of the first pedigree charts to trace an inherited illness  Albinism: homozygous recessive lacks an enzyme necessary to manufacture the pigment melanin  Pale hair and skin  Autosomal recessive

 Most of the traits Mendel studied were on different genes but some were actually on the same chromosome but at opposite ends  Genes located close to each other on the same chromosome usually do not separate during meiosis, they are linked

 Is the term indicating that two genes are not transmitted independently. Why?  Two genes physically near each other on a chromosome will not assort randomly in meiosis.

Unlinked : 4 type of gametes PL, Pl, pL, pl Types of gametes from a parent heterozygous for two genes? Tightly linked: 2 types of gametes PL and pl NOTE for LINKAGE: which two types are observed (PL and pl OR Pl and pL) depends on which alleles are on the same chromosome in the parent!

 A linkage map is a diagram indicating the relative distance between genes.  1% recombination = 1 map unit = 1 centiMorgan (cM)  Map distances are additive. % recombination between genes X and Y 10 X and Z 4 Y and Z 6 X Z Y 4 cM6 cM 10 cM

 j, k 12%  k, l 6%  j, m 9%  l, m 15%  a, c 10%  b, c 24%  a, d 30%  b, d 16%

 Mutations:  Changes in the DNA sequence that affect genetic information  Two type of mutations:  Chromosomal (changes in chromosome)  Gene (changes in a single gene)

 Affect only one nucleotide  Occur at a single point in the DNA sequence  Substitution (CAT  RAT)

 Point mutation that involves the insertion or deletion of a nucleotide  Changes the reading frame (read in 3s)  Much bigger affect on the DNA sequence

 Insertion  THE FAT CAT ATE THE RAT  THE FAT CAT EAT ETH ERA T  Deletion  THE FAT CAT ATE THE RAT  THF ATC ATA TET HER AT

 Chromosomal mutations involves changes in the number or structure of chromosomes  Types of Chromosomal Mutations:  Inversion (ABC*DEF  AED*CBF)  Deletion (ABC*DEF  AC*DEF)  Duplication (ABC*DEF  ABBC*DEF)  Translocation

 Monosomy-missing one chromosome (45)  Trisomy-one extra chromosome (47)  Ex: Down’s Syndrome (trisomy 21)  Haploid – one set of chromosomes (23)  Ex: gametes (egg or sperm)  Diploid – two sets of chromosomes (46)  Ex: body cells  Polyploid – multiple sets of chromosomes

Some allele combinations are lethal. Mexican hairless dogs result from a mutation in a gene that shows lethality  hhhairy the wild type trait  Hhhairless one mutation present creates a visible phenotype  HH dies two mutation are lethal

 Lethal is deadly, so any genotype (allele combination) that causes the death of an individual is literally lethal  In a population and evolutionary sense  It causes death before the individual can reproduce  This prevents passage of genes to the next generation  Huntington’s disease- fatal in middle age, is lethal to the individual, not the population

 In humans, early acting lethal alleles cause  Spontaneous abortions  When a man and a woman each carry a recessive allele (lethal) each pregnancy has a 25% chance of a miscarriage

 A person only has two alleles for any autosomal gene, but  A gene may exist in more than two allelic forms in a population, because  Genes can mutate in many ways at any nucleotide in their DNA sequence  Different allele combinations produce variations in phenotype

 Phenylketonuria (PKU) is an inborn error in metabolism  When the enzyme is absent: mental retardation  The amino acid phenylalanine that the enzyme normally breaks down builds up in the brain cells causing mental retardation  If the individual is placed on a special diet extremely low in phenylalanine from birth until 8 years of age or longer, it is possible to allow for normal brain development  There are more than 300 mutant alleles for this gene to combine to form four basic phenotypes  Classic PKU: mental retardation  Moderate PKU  Mild PKU  Excreting excess of the amino acid in the urine, no symptoms

 The heterozygous phenotype is typically intermediate to the homozygous phenotype  On the whole body level, Tay-Sachs disease displays complete dominance because the heterozygote is a carrier.  If phenotype is based on the enzyme level, then the heterozygote is between the homozygote dominant (full enzyme level) and homozygote recessive (no enzyme) indicates the heterozygous phenotype is distinct from either homozygous phenotype.

 This example is more obvious.  The pink flower is due to an intermediate amount of pigment

 Familial hypercholesterolemia (FH) shows incomplete dominance on both the molecular and whole-body levels  A person with two-disease causing alleles lacks receptors on liver cells that take up cholesterol from the bloodstream  Die as children of a heart attack  A person with one-disease allele has half the normal number of receptors  May suffer heart attacks in middle age  Two wild type alleles has the normal receptors  Do not develop this inherited form of heart disease

The ABO gene encodes a cell surface protein.  Allele A makes A protein  Allele B makes B protein  Allele O makes no protein  (missing one DNA nucleotide) Alleles A and B can be present on the cell surface at the same time.  Alleles A and B are codominant.  Allele O is recessive to both A and B alleles.

 when one gene masks or affects the expression of a second gene. Is a result of two interacting genes: the I and H genes  H protein attaches the A or B protein to the cell surface.

 The normal H allele encodes for an enzyme that inserts a sugar molecule, antigen H, onto a glycoprotein on the surface of an immature RBC  Fucosyltranserase 1 The H gene is called FUT1  The recessive h allele produces an inactive form of the enzyme-no insertion  The A and B antigens are attached to the H antigen  Therefore as long as there is at least one H allele pr4esent the ABO genotype dictates the ABO blood type  hh genotype there is no H antigen and A and B antigens cannot attach: The person has O blood based on phenotype but, may have any ABO genotype

 A gene does not act alone at times  Nutrition  Toxic exposures  Illnesses  Actions of other genes  Influence the expression of most genes  Two individuals who have the most severe genotype for CF and one is much sicker  She is sicker because she has also inherited genes predisposing her to develop asthma and respiratory allergies

 Two terms you need to know  Penetrance  Refers to the all or none expression of a genotype  Expressivity  Refers to severity or extent  This cause Mendelian traits and illnesses to have distinct phenotypes  Penetrant allele combination  Huntington disease: all will develop symptoms if they live long enough

 Incomplete penetrant occurs if some individuals do not express the phenotype  No symptoms  Polydactyly  A phenotype is variably expressive if symptoms vary in different people  Polydactyly  Familial hypercholesterolemia  FH heterozygote can develop heart disease due to high serum cholesterol in middle age, but, healthy diet and exercise can delay symptoms

A phenotype that varies in intensity shows variable expressivity. Incomplete penetrance Occurs when the disease phenotype is not always observed among individuals carrying the disease-associated genotype. DD or Dd80% polydactyly DD or Dd20% no polydactyly FF or Ffall show mild, moderate or profound deafness

 One gene controls or influences the expression of many symptoms in a disorder. These symptoms may be variably expressed.  Porphyria variegata an autosomal dominant, inborn error of metabolism  Read page 98 about the royal family of King George III Photo © North Wind Picture Archives

A trait caused by the environment that mimics an inherited condition. Exposure to teratogens  Thalidomide causes limb defects akin to rare inherited phocomelia. Infection  Rubella in pregnant mothers causes deafness mimicking inherited forms of deafness.

Individuals with identical phenotypes may reflect different genetic causes.  Deafness  Albinism  Cleft palate  Poor blood clotting Different genes can produce identical phenotypes.

AUTOSOMAL RECESSIVE

 Lack of pigment in skin, hair, and nails

 Excess mucus in lungs, digestive tract, liver  Increased susceptibility to infections  Death in childhood unless treated

 Accumulation of galactose (sugar) in tissues  Mental retardation  Eye and liver damage

 Accumulation of phenylalanine in tissues  Lack of normal skin pigment  Mental retardation

 Lipid accumulation in brain cells  Mental deficiency  Blindness  Death in early childhood

AUTOSOMAL DOMINANT

 dwarfism

 Mental deterioration and uncontrollable movements  Appears in middle age

 Excess cholesterol in blood  Heart disease

CODOMINANT ALLELES

 Sickled red blood cells  Damage to many crisis  Mutation in the coding for hemoglobin

SEX-LINKAGE

 Inability to distinguish certain colors

 A protein necessary for normal blood clotting is missing  Can be treated with injections

 Progressive weakening of the skeletal muscle

CHROMOSOMAL

 Trisomy 21  Mild to severe retardation  Increased susceptibility to disease

 Female with XO  No secondary sex characteristics  Unusual physical stature  sterile

 Male with XXY  No secondary sex characteristics  Slight mental retardation  sterile

 Dominant/Recessive  Incomplete Dominance  Codominance  Sex-Linkage  Chromosome Mapping  Pedigree Analysis  Probability  Chi-square analysis  Mutations  Epistasis