Classical (Mendelian) Genetics

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Classical (Mendelian) Genetics
Gregor Mendel
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Vocabulary

• Genetics The scientific study of heredity
• Allele Alternate forms of a gene/factor.
• Genotype combination of alleles an organism has.
• Phenotype How an organism appears.
• Dominant An allele which is expressed (masks the
  other).
• Recessive An allele which is present but remains
  unexpressed (masked)
• Homozygous Both alleles for a trait are the
  same.
• Heterozygous The organism's alleles for a trait
  are different.

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History

• Principles of genetics were developed in the mid
  19th century by Gregor Mendel an Austrian Monk
• Developed these principles without ANY scientific
  equipment - only his mind.
• Experimented with pea plants, by crossing various
  strains and observing the characteristics of
  their offspring.
• Studied the following characteristics
• Pea color (Green, yellow)
• Pea shape (round, wrinkled)
• Flower color (purple, white)
• Plant height (tall, short)
• MONOHYBRID CROSS- cross fertilizing two organisms
  that differ in only one trait
• SELF-CROSS- allowing the organism to self
  fertilize (pure cross)

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MENDELS CROSSES

• Started with pure plants ( P1)
• Then made a hybrid of two pure traits
• P1 X P1

• Made the following observations (example given is
  pea shape)
• When he crossed a round pea and wrinkled pea, the
  offspring (F1 gen.) always had round peas.
• When he crossed these F1 plants, however, he
  would get offspring which produced round and
  wrinkled peas in a 31 ratio.

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Laws of Inheretance

• Law of Segregation When gametes (sperm egg etc)
  are formed each gamete will receive one allele or
  the other.
• Law of independent assortment Two or more
  alleles will separate independently of each other
  when gametes are formed

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Punnett Squares

• Genetic problems can be easily solved using a
  tool called a punnett square.
• Tool for calculating genetic probabilities

A punnett square
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Monohybrid cross (cross with only 1 trait)

• Problem
• Using this is a several step process, look at the
  following example
• Tallness (T) is dominant over shortness (t) in
  pea plants. A Homozygous tall plant (TT) is
  crossed with a short plant (tt). What is the
  genotypic makeup of the offspring? The phenotypic
  makeup ?

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Punnet process

1. Determine alleles of each parent, these are given
   as TT, and tt respectively.
2. Take each possible allele of each parent,
   separate them, and place each allele either along
   the top, or along the side of the punnett square.

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Punnett process continued

• Lastly, write the letter for each allele across
  each column or down each row. The resultant mix
  is the genotype for the offspring. In this case,
  each offspring has a Tt (heterozygous tall)
  genotype, and simply a "Tall" phenotype.

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Punnett process continued

• Lets take this a step further and cross these F1
  offspring (Tt) to see what genotypes and
  phenotypes we get.
• Since each parent can contribute a T and a t to
  the offspring, the punnett square should look
  like this.

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Punnett process continued

• Here we have some more interesting results
  First we now have 3 genotypes (TT, Tt, tt) in a
  121 genotypic ratio. We now have 2 different
  phenotypes (Tall short) in a 31 Phenotypic
  ratio. This is the common outcome from such
  crosses.

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Dihybrid crosses

• Dihybrid crosses are made when phenotypes and
  genotypes composed of 2 independent alleles are
  analyzed.
• Process is very similar to monohybrid crosses.
• Example
• 2 traits are being analyzed
• Plant height (Tt) with tall being dominant to
  short,
• Flower color (Ww) with Purple flowers being
  dominant to white.

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Dihybrid cross example

• The cross with a pure-breeding (homozygous)
  Tall,Purple plant with a pure-breeding Short,
  white plant should look like this.

F1 generation
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Dihybrid cross example continued

• Take the offspring and cross them since they are
  donating alleles for 2 traits, each parent in the
  f1 generation can give 4 possible combination of
  alleles. TW, Tw, tW, or tw. The cross should
  look like this. (The mathematical foil method
  can often be used here)

F2 Generation
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Dihybrid cross example continued

• Note that there is a 9331 phenotypic ratio.
  9/16 showing both dominant traits, 3/16 3/16
  showing one of the recessive traits, and 1/16
  showing both recessive traits.
• Also note that this also indicates that these
  alleles are separating independently of each
  other. This is evidence of Mendel's Law of
  independent assortment

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PROBABILITY

• Definition- Likelihood that a specific event will
  occur
• Probability number of times an event happens
• number of opportunities for event
  to happen

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What if you dont know the GENOTYPE?
Perform a TEST CROSS- cross with a homozygous
recessive individual
If no recessive traits appear than unknown
individual was HOMOZYGOUS DOMINANT
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TEST CROSS

• If the unknown individual was heterozygous than
  50 of the offspring should have the recessive
  phenotype.

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INCOMPLETE DOMINANCE

• When neither allele is completely recessive
• Example RR ---- red roses
• rr---------- white roses
• Rr-------pink roses
• In the HETEROZYGOUS individual both alleles are
  still visible but not fully visible

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Other Factors Incomplete Dominance

• Some alleles for a gene are not completely
  dominant over the others. This results in
  partially masked phenotypes which are
  intermediate to the two extremes.

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Other Factors Continuous Variation

• Many traits may have a wide range of continuous
  values. Eg. Human height can vary considerably.
  There are not just "tall" or "short" humans

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CODOMINANCE

• When the HETEROZYGOUS INDIVIDUAL fully shows both
  alleles.
• Example is blood type
• Blood Type A is dominant
• Blood Type B is dominant
• Blood Type O is recessive to both A and B

Blood Type AB- is heterozygous for A and B
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Multiple Alleles

• Phenotypes are controlled by more than 2
  variances for a trait
• ABO Blood typing
• Humans have multiple types of surface antigens on
  RBC's
• The nature of these surface proteins determines a
  person's Blood Type.
• There are 3 alleles which determine blood type
  IA, IB, or IO. This is referred to as having
  multiple alleles
• Human blood types are designated as A, B or O.
• Type A denotes having the A surface antigen, and
  is denoted by IA
• Type B denotes having the B surface antigen, and
  is denoted by IB
• Type O denotes having neither A or B surface
  antigen, and is denoted by IO
• There are several blood type combinations
  possible
• A
• B
• AB (Universal recipient)
• O (Universal donor)

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Punnett Square for blood typing
A
O
A
B
AB
BO
O
AO
OO
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Blood Immunity

• A person can receive blood only when the donor's
  blood type does not contain any surface antigen
  the recipient does not. This is because the
  recipient has antibodies which will attack any
  foreign surface protein.
• Thus, Type AB can accept any blood types because
  it will not attack A or B surface antigens.
  However, a type AB person could only donate blood
  to another AB person. They are known as Universal
  Recipients.
• Also, Type O persons are Universal donors because
  they have NO surface antigens that recipients'
  immune systems can attack. Type O persons can
  ONLY receive blood from other type O persons.
• There is another blood type factor known as Rh.
• People are either Rh or Rh- based on a basic
  dominant/recessive mechanism.
• Not usually a problem except with pregnancy.
• It is possible that an Rh- mother can carry an
  Rh fetus and develop antibodies which will
  attack destroy the fetal blood
• This usually occurs with 2nd or 3rd pregnancies,
  and is detectable and treatable.

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Other Factors

• Gene interaction
• Many biological pathways are governed by multiple
  enzymes, involving multiple steps.(Examples the
  presence of a HORMONE) If any one of these steps
  are altered. The end product of the pathway may
  be disrupted.
• Environmental effects
• Sometimes genes will not be fully expressed owing
  to external factors. Example Human height may
  not be fully expressed if individuals experience
  poor nutrition.

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Chapter 12--Sex Linkage

• All chromosomes are homologous except on sex
  chromosomes.
• Sex chromosomes are either X or Y.
• If an organism is XX, it is a female, if XY it is
  male.
• If a recessive allele exists on the X chromosome.
  It will not have a corresponding allele on the Y
  chromosome, and will therefore always be
  expressed

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PEDIGREE ANALYSIS

• is an important tool for studying inherited
  diseases
• uses family trees and information about affected
  individuals to
• figure out the genetic basis of a disease or
  trait from its inheritance pattern
• predict the risk of disease in future offspring
  in a family (genetic counseling)

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• How to read pedigrees
• Basic patterns of inheritance
• 1. autosomal, recessive
• 2. autosomal, dominant
• 3. X-linked, recessive
• 4. X-linked, dominant (very rare)

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How to read a pedigree
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Sample pedigree - cystic fibrosis
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Autosomal dominant pedigrees
1. The child of an affected parent has a 50
chance of inheriting the parent's mutated allele
and thus being affected with the disorder. 2. A
mutation can be transmitted by either the mother
or the father. 3. All children, regardless of
gender, have an equal chance of inheriting the
mutation. 4. Trait does not skip generations
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Autosomal dominant traits

• There are few autosomal dominant human diseases
  (why?), but some rare traits have this
  inheritance pattern

ex. achondroplasia (a sketelal disorder causing
dwarfism)
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AUTOSOMAL RECESSIVE

• 1. An individual will be a "carrier" if they
  posses one mutated allele and one normal gene
  copy.
• 2. All children of an affected individual will be
  carriers of the disorder.
• 3. A mutation can be transmitted by either the
  mother or the father.
• 4. All children, regardless of gender, have an
  equal chance of inheriting mutations.
• 5. Tends to skip generations

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Autosomal recessive diseases in humans

• Most common ones
• Cystic fibrosis
• Sickle cell anemia
• Phenylketonuria (PKU)
• Tay-Sachs disease

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Autosomal Recessive
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X-Linked Dominant

• 1. A male or female child of an affected mother
  has a 50 chance of inheriting the mutation and
  thus being affected with the disorder.
• 2. All female children of an affected father will
  be affected (daughters possess their fathers'
  X-chromosome).
• 3. No male children of an affected father will be
  affected (sons do not inherit their fathers'
  X-chromosome).

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X-LINKED Recessive

• 1. Females possessing one X-linked recessive
  mutation are carriers
• 2. All males possessing an X-linked recessive
  mutation will be affected (why?)
• 3. All offspring of a carrier female have a 50
  chance of inheriting the mutation.
• 4. All female children of an affected father will
  be carriers (why?)
• 5. No male children of an affected father will be
  affected

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Sex linkage example

• Recessive gene for white eye color located on the
  Xw chromosome of Drosophila.
• All Males which receive this gene during
  fertilization (50) will express this.
• If a female receives the Xw chromosome. It will
  usually not be expressed since she carries an X
  chromosome with the normal gene

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Human Sex Linkage

• Hemophilia
• Disorder of the blood where clotting does not
  occur properly due to a faulty protein.
• Occurs on the X chromosome, and is recessive.
• Thus a vast majority of those affected are males.
• First known person known to carry the disorder
  was Queen Victoria of England. Thus all those
  affected are related to European royalty.

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LINKAGE GROUPS (pg 222)

• Definition- genes that are located on the same
  chromosome.
• Discovered by Thomas Hunt Morgan. Made a
  dihybrid cross with heterozygous fruit flies (
  Gray body and Long wings)
• GgLl x GgLl predicted a 9331 ratio
• What ratio did he get?

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Answer

• He only got two combinations.
• Gray body with long wings - DOMINANT
• white body with short wings- RECESSIVE
• And they were in a 31 ratio just like a standard
  MONOHYBRID cross.
• Conclusion these GENES must be on the same
  chromosome.

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Further studies of Morgan

• Wanted to find out which traits were linked
  together on the same chromosome.
• Linked many traits together (remember that fruit
  flies have only 4 chromosomes)

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During his many linkage studies found some
mutations

• While working with the gray body and long wing
  linkage.
• Occasionally he had some flies come out Gray body
  with short wings and
• White body with long wings
• How could this be?

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CROSSING OVER- forms new genetic combinations
Long wings
White body
Gray body
Short wings
Long wings
White body
Short wings
Gray body
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CHROMOSOME MAPPING

• New question- where are the genes located on a
  chromosome?
• How far apart are the genes on a chromosome?

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Using the rate of CROSSING OVER to determine
location.
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CHROMOSOME MAPPING

• The PERCENTAGE of crossing over is equal to ONE
  MAP UNIT on a chromosome.

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