Mendelian Genetics 2010 by xiangpeng


									Which of the following
disorders is fake?
   “Werewolf Syndrome”
       Congenital generalized hypertrichosis – a rare
        disorder characterized by excessive hair growth
        on the face and the upper body
   “Vampire Syndrome”
       Familial photodermatitis - When exposed to the
        sun, the skin blisters and gives pain, drinking
        blood relieves symptoms
   “Blue-Skin Syndrome”
       Methomoglobinemia – the enzyme diaphorase is
        absent from the red blood cells, and doesn’t allow
        for the conversion from methomoglobin back to
   Vampire syndrome is the FALSE

Congenital generalized hypertrichosis…
The Fugate family of Troublesome Creek,Kentucky…
 Analyzing Heredity
    Heredity: the transmission of traits from
     parents to offspring
    Ideas of heredity have been around for all
     of recorded history
        It’s always been noticeable that children
         resemble their parents
    Sometimes characteristics are so
     noticeable that they can be traced for many
    There are several famous examples…
   The Hapsburgs, the ruling family of Austria (1200s – WWI)
       One relative, the Archduke Francis Ferdinand, was shot by a
        Serbian rebel. This assassination began WWI.
       The “Hapsburg Lip” was a protruding lip that’s
        evident in portraits of the family that span over
        400 years…
   Royal families of Europe,
    beginning with Queen
    Victoria of England
       Passed on hemophilia
           Excessive bleeding due to
            an ineffective clotting
       It was passed on to the
        families of other nations as
        Victoria’s ancestors were
        married to others of their
        social status
1800’s: Most scientists believed in a
blending of inheritance
White rabbit + Black rabbit =
Gray rabbit
This didn’t hold true
Basic Vocabulary before we begin:

   Chromosomes
   Genes
   Alleles
   Heterozygous
   homozygous
Genetic Symbols
     Female symbol:
         Represents the hand
          mirror & comb of

     Male symbol:
         Represents the shield
          & spear of Mars
Gregor Mendel

   1822: Born into a low-
    income family in what would
    become Czechoslovakia
   Entered the monastery to
    receive an education
   Eventually became an abbot
    for the church, meanwhile
    carried on experiments
Mendel, cont’d…

   Was creative in his approach to science
     Took quantitative (numerical) data
      and analyzed it mathematically
   His work was ignored until after his
   Mendel worked with Pisum sativum, garden peas, to study
     they come in a many varieties

     The male and female parts are in the same flower – an

      individual can self-pollinate itself or cross-pollinate with
      another individual
Mendel’s Monohybrid Traits
 Mendel’s Experiments:
1.       He allowed each variety (ex:
         purple-flowered vs. white-
         flowered) to self-pollinate for
         several generations
           Each was true-bred for a
            particular trait (seed shape,
            flower color, etc)
           He called these true-bred
            plants his parental, or P,
1.    (P generation)
2.   He crossbred two          P:         x
     varieties from the P
     generation… called
     the offspring the first
     filial, or F1,
3.   Allowed the F1                 F1:
     generation to self-
     pollinate… called the
     offspring the second
     filial, or F2,
Monohybrid Cross – a cross that tracks a single trait
(ex: flower color)

   P generation:                 x

                                      All purple
                                       -called purple
            F1 generation:
                                       -called white

                                              -705 purple
   F2 generation:
                                              -224 white
                                                ~ 3:1 ratio

   When Mendel self-pollinated the white
    flowered F2 individuals, ALL offspring were
   When he self-pollinated the purple F2
    individuals, he found only 1/3 to be true-
       The other 2/3 gave another 3:1 ratio of p:w
   From this he devised a theory…
Mendel’s Theory:
1.   Parents pass on
     genes, not
     necessarily traits
2.   Alternative forms of a
     gene that govern a
     specific trait ( hair
     color) are called
     alleles and are
     represented by by
     lower case or          In this plant,
     capitalized letters.   these might be
     (H,h)                  the individual’s
                             two genes for
                             flower color
Remember, chromosomes come in homologous
pairs, which have the same types of genes, but not
the exact same genes, since one chromosome in
each pair is from the mother of the organism, one
is from the father.
Chromosome 1     2                    Chromosome 3   4

 Eye color
                         Homologous Pair =
                         2 chomosomes with
 Height                                                  Lips
                         same genes

 Hair Color

Chromosomes 1 and 3 were from Mom, 2 and 4 were from Dad.
 …more theory
3. For every trait, an individual has two genes
      -If the alleles are the same, it is “homozygous.”
     -If they are different, it is “heterozygous.”
4. Your set of alleles is your genetic make-up or
    “genotype.” Your appearance is your “phenotype.”
5. You get one allele for each trait from each parent,
    and then pass on one of these two to each child.
6. In heterozygous individuals, only the dominant allele
    is expressed. The recessive allele is there but is not
*It should be noted that in humans, over 600 traits have
been shown to be single-factor inheritance traits, like
those seen in peas.
*Many others, however, are “polygenic” and have several
more factors involved…
   Mendel’s Two Laws:
     Law of Segregation: The members of each
      pair of alleles separate when gametes form
       You only give one of each homologous pair

        of chromosomes to each gamete
   Law of Independent Assortment: Pairs of alleles
    separate independently (ex: flower color is independent
    of seed color)
     Exception to the rule: We now know this does not
       hold true if both genes are located on
       the same chromosome!

        Whatever these
        two genes code
        for, they will be
        passed on
        together because
        they are part of the
        same chromosome
Analyzing Heredity
   Capital letters represent dominant alleles
   Lower-case letters represent recessive alleles

What is dominance?
A dominant gene is the gene that is
 expressed in an individual who has both
 alleles of that gene.
For example, a heterozygous individual with a
 gene for purple color and a gene for white
 color expresses the purple gene and
 therefore appears purple.
(dominance demo)
Is “dominant” the same as “common” or
   No. Many genes are rare but dominant.
    Dwarfism and polydactyly (having more than
    5 fingers) are both dominant traits, but only
    1/400 babies is born with a 6th finger.
 Probability = the likelihood that an event will occur, or
 # of occurrences of a targeted event

 total # of occurrences
Use the rule of multiplication when you need to find the
  probability of two or more independent events.
 Chance of a coin landing heads… ½

 Chance of a coin landing heads, then tails…

 Chance of a coin, in two tosses, landing heads once and
  tails once…
          (½ x ½) + (½ x ½) = ¼ + ¼ = ½
         H then T or T then H
Monohybrid Cross
   One way to analyze is the Punnett square (named
    after the inventor, Reginald Punnett)
    T = tall pea plant
    t = short pea plant          genotype: TT x tt
                                 phenotype: tall x short
             T      T
          t Tt     Tt            4 out of 4 offspring (ALL)
                                 will be Tt, tall
          t Tt     Tt
   Tt x Tt

          T    t
         T TT Tt
         t Tt tt

   1 out of 4 will be TT, tall
    2 out of 4 will be Tt, tall
    1 out of 4 will be tt, short

   1 : 2 : 1 genotypic ratio… 3 : 1 phenotypic ratio
    TT : Tt : tt                tall : short
Single Factor Inherited Traits
in Humans
  Tongue    rolling

  Hitchhiker’s   thumb


  Widow’s    Peak

  Ear   lobes (attached or free)
Dihybrid Cross – a cross involving two pairs of
            P: purple p: white T: tall   t: short
                 TtPp x TtPp

         TP        Tp    tP   tp
    TP    TTPP     TTPp TtPP TtPp
    Tp    TTPp     TTpp TtPP Ttpp
    tP     TtPP    TtPp ttPP ttPp
    tp    TtPp     Ttpp ttPp ttpp
   9:3:3:1 ratio
    purple/tall : purple/short : white/tall : white/short
Complex Patterns of Heredity –   exceptions
to what we have learned

   Incomplete Dominance:
    when neither allele is
    dominant or recessive
     Ex: snapdragons

              r = red
              w = white
        *rw individuals
        are pink
   Codominance: multiple
    dominant alleles exist that
    can be expressed at the
    same time
       ex: red & white hairs are both
        dominant in horses
         Hr = red
         Hw = white

        *HrHw individuals are “roan”
          colored (have both fully
          red and fully white hairs)
   Continuous Variation: when several genes
    influence a trait
     ex: in humans, height shows continuous

      variation… you don’t have just short vs. tall
      people – you have a continuous range
     ex: skin color: 3 hypothetical genes for skin
      coloration. The “dark skin” allele for each gene
      (A,B,C) contributes one unit of darkness to the
      phenotype. So, a person that is AABBCC would be
      very dark, while a person with aabbcc, would be very
      light. Those people with AaBbCc would be in the
   Pleiotropy: When one gene has multiple
     ex: Sickle-cell – blood can’t carry oxygen

      well; resistance to malaria
   Epistasis: one gene has the ability to turn off
     ex: in mice, black is dominant over brown (B
      = black, b = brown)
        There’s another gene that simply codes for the
         ability to produce pigment in the first place (C =
         pigment, c = no pigment / albino)
        Bbcc  no color (albino)
        BbCc  black
   Environmental Influences:
    phenotype can depend on the
    surroundings (while the
    genotype does not)
       ex: the color of the arctic
        fox changes from brown
        during the summer time to
        white during the winter for
       ex: During development,
        the colder parts of a
        Siamese cat turn a darker
        color, while the warmer
        parts retain more of a white
Sex-Linked Traits

   Sex-linked traits are carried on the X
    chromosome, and are recessive
   An example is hemophilia
   A man with hemophilia is NOT just “hh”
   He only has ONE X chromosome. He is
    represented as XhY.
   Men are much more likely to have sex-linked
    traits, because they only have one chance
    (one X) to get the healthy allele!
   Color blindness is another sex-linked trait
   Q: A woman who is a carrier for color-blindness has a
    child with a healthy man. What are the chances they
    will have a child who is color-blind?
   A: The woman is XBXb. The man is XBY.
   The punnett square looks like this:
                  XB          Xb

          XB   XBXB        XBXb

          Y     XBY         X bY     ¼ chance.
Tests for Colorblindness

A person with normal vision will see a 5.
A person with red/green colorblindness will see a 2.
Human Genetics

   Family pedigrees can be analyzed:

       = female                 = female carrier

       = male                   = male carrier

       = female with disorder

       = male with disorder
Sample pedigree chart…

   A horizontal
   line signifies
   marriage, or
       A vertical
       children, or
                      Bracket, overhead
                      connections signify siblings
Pedigree Analysis…

                     •Is this trait
                     dominant or
Pedigree analysis…

                     It must be
                     because if it
                     was dominant
                     the parents
                     would have
                     had the trait as
More pedigree analysis…

                          What type
                          does this
                          most likely
This is most
likely a
   Remember: genes code for proteins that have a
    specific function
   For many genes, there may be only one allele
       Example: If all humans make the protein keratin the same
        way, with no variation, then this allele may only exist as a “K”
   New alleles come about via mutations
     Mutations, caused by “mutagens,” usually have
       harmful effects (although beneficial effects are possible)
    Harmful effects of mutations are what cause genetic
     These disorders can be either dominant or
       recessive, and can strike at various points in life
   If a trait or a disorder is not sex-linked it is
Recessively inherited disorders:
   Heterozygous individuals are “normal” in
       The disorder shows up only in homozygous
        recessive individuals (ex: aa, but not Aa)
   Disorders are often distributed only among
    certain ethnicities. Why?
   During less technological and global periods of
    time, societies were more isolated
     If an altered gene (mutation) popped up
      somewhere, it would stay within that society
      until individuals migrated in or out and mixed
      with other populations
   1 in 25 caucasians is a carrier of cystic
    fibrosis. What are the chances that someone
    with an African-American mother and a white
    father is a carrier?
   (1/25) x (1/2) = 1/50    A 2% chance.
   Using the given numbers, what are the
    chances that two, undiagnosed white
    individuals have a child with cystic fibrosis?
   (1/25) x (1/25) = 1/625 chance they are both
    carriers (Cc & Cc)
   (1/625) x (1/4) = 1/2500 chance their child will
    have cystic fibrosis... A 0.04% chance.
   A man named John and a woman named Carol each
    had a sibling who died of a lethal, recessive disorder.
    Neither of them has the disorder, but they have not
    been tested to see if they are carriers. What are the
    chances that they will have a child with the disorder?
   Their parents must have each been Tt & Tt, which gave
    a 1TT:2Tt:1tt ratio of children
   This means there is a 2/3 chance that each is a carrier
   (2/3) x (2/3) = 4/9 chance that both are carriers
    (Tt x Tt)
   (4/9) x (1/4) = 1/9 chance their child will have the
   For the most part, it is always very unlikely that two
    carriers for the same rare disorder will meet and have
   These chances are greatly increased when individuals
    are related
       Called “sanguineous” (same-blood) matings, and are indicated
        in pedigrees with a double line
   Rules and laws, present in numerous societies for
    thousands of years, came about through the
    observation that stillbirths and birth defects are much
    more common when parents are related
   Such effects are observable in many domesticated
    animals and endangered populations
   Ex: Many pure-bred dogs suffer disorders (deafness in
   Ex: Florida panthers have a crooked tail
    Dominant Disorders
   Why are dominant disorders more rare than
    recessive disorders?
   Unless it strikes late in life (like Huntington’s),
    an individual who carries even one of the alleles
    will have the disorder
   If it strikes before the individual has any
    children, then that person will not be able to
    pass on the allele and the mutation will stop with
    Multifactorial Disorders

   Diseases with a multifactorial basis involve a
    genetic component but also a significant
    environmental influence
   Includes heart disease, diabetes, cancer,
    alcoholism, and many mental illnesses
   Lifestyle has a very large effect
       Ex: exercise, a healthy diet, abstinence from smoking,
        and dealing well with stress all greatly reduce the risk
        of heart disease
    Well-Known Genetic Disorders:

   Cystic fibrosis – mucus clogs lungs, liver, pancreas (European)
   Sickle cell anemia – poor blood, oxygen circulation (African)
   Tay-Sachs disease – deterioration of CNS (Jews)
   Phenylketonuria – Failure of brain to develop
   Hemophilia – Failure of blood to clot
   Huntington’s Disease – Deterioration of brain tissue
   Muscular Dystrophy – Wasting away of muscle
   Marfan Syndrome – disproportional growth, early death
   Achondroplasia – one form of dwarfism
Dominant or Recessive?


               Tt   Tt

          tt             TT or Tt
Dominant or Recessive?

Explanation: Could be either dominant or
Dominant or Recessive?


              Tt   Tt

   TT or Tt             tt
NO (at least not sex-linked recessive).

Explanation: If the mother were XhXh, then
 each of her
 sons would
 have to be
 XhY and
 show the
 trait. They do not, and so it cannot be sex-

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