Mendel and the Gene Idea by zhangyun


									Mendel and the
Gene Idea
Chapter 14
1.    Historical view
2.    Work of Mendel
     A.   Principle of Segregation
     B.   Independent Assortment
     C.   Probability
3.    Extending Mendel
     A.   Intermidiate inheritance
     B.   Multiple Alles
     C.   Pleiotrophy
     D.   Polygenic inheritance
4.    Mendelian Inheritance in Humans
     A.   Human Pedigree
     B.   Recessive Disorders
     C.   Dominant Disorders
     D.   Genetic testing
 The History Of Genetics

Pythagoras 500
B.C., a Greek
stated that
human life began
with male and
female fluids
The History Of Genetics
Aristotle furthered
 this idea and
 suggested that
 these fluids, or
 ―semens,‖ were
 actually purified
 blood must be part
 of heredity.
Historical View
 Hippocrates  and Aristotle proposed
  the idea of what they called
  pangenes, which they thought were
  tiny pieces of body parts.
 They thought that pangenes came
  together to make up the
  homunculus, a tiny pre-formed
  human that people thought grew into
  a baby
Antonie van Leeuwenhoek
 In the 1600s, the development of the
  microscope brought the discovery of
  eggs and sperm
 thought he saw the homunculus curled up
  in a sperm cell.
 His followers believed that the
  homunculus was in the sperm, the father
  ―planted his seed,‖ and the mother just
  incubated and nourished the homunculus
  so it grew into a baby
       One Bizarre Theory
•The theory of Homunculus
-17th century
•sex cells contained a
complete miniature adult,
perfect in form
•This statement was
popular way into the 18th   Small
century                     individual
Regnier de Graaf
 He and his followers thought that they
  saw the homunculus in the egg, and the
  presence of semen just somehow
  stimulated its growth
 In the 1800s, a very novel, ―radical‖ idea
  arose: both parents contribute to the
  new baby, but people (even Darwin, as he
  proposed his theory) still believed that
  these contributions were in the form of
Genetic Principles
   Drawing from the Deck of Genes?
   What accounts for the transmission of
    traits from parents to offspring?
―Blending‖ Hypothesis

 Possible explanation of heredity is a
  ―blending‖ hypothesis
 The idea that genetic material
  contributed by two parents mixes in a
  manner analogous to the way blue and
  yellow paints blend to make green
―Particulate‖ Hypothesis
   An alternative  the gene idea
       Parents pass on discrete heritable units,
Modern Genetics
    Traces the beginnings to Gregor Mendel, an
    Austrian monk, who grew peas in a monastery
   Was unique among biologists of his time
    because he quantifiable data, and actually
    counted the results of his crosses.
   Published his findings in 1865  people didn’t
    know about mitosis and meiosis, so his
    conclusions seemed unbelievable
    His work was ignored until it was rediscovered
    in 1900 by a couple of botanists who were
    doing research on something else.
    Gregor Mendel
                                               Figure 14.1

   Documented a particulate mechanism of inheritance
    through his experiments with garden peas
   He discovered the basic principles of heredity
    breeding garden peas in carefully planned
   Chose to track
        Only those characters that varied in an ―either-or‖
   Made sure that
        He started his experiments with varieties that were
    Genetic Vocabulary
   Character: a heritable feature, such as flower
   Trait: a variant of a character, such as purple
    or white flowers
   The true-breeding parents
       Are called the P generation
   The hybrid offspring of the P generation
       Are called the F1 generation
   When F1 individuals self-pollinate
       The F2 generation is produced
 Phenotype   Physical appearance
 Genotype Genetic makeup
 Dominant trait that is easily
 Recessive  trait that is often
 Homozygous2 alleles for a trait are
  identical  TT or tt
 Heterozygous – 2 alleles for a trait
  are not identical  Tt
Alternative forms of a gene
which determines a trait.
Alleles cont.

 Uppercase  (Capital) letters for
  dominant traits
 Lowercase letters for recessive
 Ex: tall = T short = t,
  expressed in pairs TT, Tt, tt
Why peas?
 Rapid reproduction
 Presence of
  distinctive traits
 Closed structure of
  flowers (each pea plant
    has male (stamens) and
    female (carpal) sexual
    organs)allows self-
Seven Traits Studied by Mendel
    The Law of Segregation
   When Mendel crossed contrasting, true-
    breeding white and purple flowered pea
       All of the offspring were purple
   When Mendel crossed the F1 plants
       Many of the plants had purple flowers, but
        some had white flowers
    Mendel’s Experiment
   Crossed pure purple
    and a pure white
    flower (P
    generation) =F1
   All F1 plants
    (purple) are
    crossed by self
    pollination = F2
    generation yields
    ¾ purple and ¼
The Testcross
 In pea plants with purple flower
   The genotype is not immediately
 Allows us to determine the
  genotype of an organism with the
  dominant phenotype, but unknown
The Testcross
 Individual with dominant phenotype
   not possible to predict the
  genotype run a test cross with
  individual with recessive phenotype
  to determine the allele
 Dominant Phenotype purple flower
  (genotype PP or Pp)
 Recessive Phenotype  white flower
  ( genotype pp)
Test Cross
The Law of Independent
   Mendel derived the law of segregation
       By following a single trait
   The F1 offspring produced in this cross
       Were monohybrids, heterozygous for one
   How are two characters transmitted from
    parents to offspring?
     As a package?
     Independently?
    Dihybrid Cross
   Mendel identified his second law of
       By following two characters at the same
   Crossing two, true-breeding parents
    differing in two characters
       Produces dihybrids in the F1 generation,
        heterozygous for both characters
   The Y and R alleles and
    y and r alleles stay
   F1 offspring would
    produce yellow, round
   The F2 offspring would
    produce two
    in a 3:1 ratio, just like a
    monohybrid cross.
   If the two pairs of
    alleles segregate
    independently of each
   Four classes of
    gametes (YR, Yr, yR,
    and yr) would be
    produced in equal
   These combinations
    produce four distinct
    phenotypes in a
    9:3:3:1 ratio
   Using the information from a dihybrid
    cross, Mendel developed the law of
    independent assortment
     Each pair of alleles segregates
      independently during gamete formation
Punnett Square

 Diagram which
 shows the
 outcome of a
   Fractions or ratios that will predict that an
    event will occur
                                    Rr                                                             Rr
                           Segregation of                                                     Segregation of
                          alleles into eggs                                                  alleles into sperm


                                          1⁄           R              1⁄                r
                                               2                           2

                                                   R                       R
                      1⁄            R                       R                           r

                                                       1⁄                      1⁄
                                                            4                       4

                                                   r                       r
                           1⁄       r                       R                           r
                                                       1⁄                           1⁄
                                                            4                            4
            Figure 14.9
The Multiplication and Addition Rules
Applied to Monohybrid Crosses

   The multiplication rule
       States that the probability that two or
        more independent events will occur
        together is the product of their individual
   The rule of addition
       States that the probability that any one
        of two or more exclusive events will occur
        is calculated by adding together their
        individual probabilities
Extending Mendel
   The inheritance of characters by a
    single gene
     May deviate from simple Mendelian
The Spectrum of Dominance
   Complete dominance
        Occurs when the phenotypes of the
         heterozygote and dominant homozygote
         are identical

                       Incomplete Dominance

    100% Dominant/0%                     Codominant
                                         100% Dominant/100%
    Incomplete Dominance
   The phenotype of F1 hybrids is
    somewhere between the                P Generation
    phenotypes of the two parental                       Red                          
                                                                                                             CW C W

    varieties                                            CRCR

   Hheterozygotes show a distinct                              Gametes          CR         CW

    intermediate phenotype, not seen
    in homozygotes.                                                                                  Pink
     This is not blended inheritance    F1 Generation                                               CRCW

      because the traits are separable
      (particulate) as seen in further                                     1⁄         1⁄
                                                                             2          2
                                                          Gametes                CR         CR

     Offspring of a cross between
      heterozygotes will show three
      phenotypes: both parentals and
                                                                           1⁄    CR       1⁄    CR   Sperm
                                                                 Eggs        2              2

      the heterozygote.                  F2 Generation
                                                                  2   CR

     The phenotypic and genotypic                                          CR CR         CR CW

      ratios are identical, 1:2:1.                              1⁄
                                                                  2   Cw
                                                                            CR CW         CW CW
   Two dominant alleles affect the phenotype in
    separate, distinguishable ways
   The human blood group MN
       Is an example of codominance
       The M, N, and MN blood groups of humans 
        presence of two specific molecules on the surface
        of red blood cells
       Both the M & N molecules are expressed in the
        heterozygous individual
       People of group M (genotype MM) have one type
        of molecule on their red blood cells, people of
        group N (genotype NN) have the other type, and
        people of group MN (genotype MN) have both
        molecules present
1.   They range from complete dominance, through
     various degrees of incomplete dominance, to
2.   They reflect the mechanisms by which
     specific alleles are expressed in the
     phenotype and do not involve the ability of one
     allele to subdue another at the level of DNA
3.   They do not determine or correlate with the
     relative abundance of alleles in a population
The dominance/recessiveness relationships
depend on the level at which we examine
the phenotype
    Tay-Sachs disease lack a functioning
     enzyme to metabolize gangliosides (a lipid)
     which accumulate in the brain, harming brain
     cells, and ultimately leading to death.
      Children   with two Tay-Sachs alleles have the
      Heterozygotes with one working allele and
       homozygotes with two working alleles are ―normal‖
       at the organismal level, but heterozygotes produce
       less functional enzyme.
      However, both the Tay-Sachs and functional
       alleles produce equal numbers of enzyme molecules,
       codominant at the molecular level
    Frequency of Dominant Alleles
 A dominant allele does not necessarily
  mean that it is more common in a
  population than the recessive allele.
 Polydactyly individuals are born with
  extra fingers or toes, is due to an allele
  dominant to the recessive allele for five
  digits per appendage.
     However, the recessive allele is far more
     prevalent than the dominant allele in the
         399 individuals out of 400 have five digits per
    Multiple Alleles
   Most genes exist in
    populations in more
    than two allelic forms
   The ABO blood group
    in humans
       Is determined by
        multiple alleles

                       Table 14.2
Human Blood Groups
 The ABO blood groups in humans are
  determined by three alleles, IA, IB, and
 Both the IA and IB alleles are dominant
  to the i allele
 The IA and IB alleles are codominant to
  each other
 Because each individual carries two
  alleles, there are six possible genotypes
  and four possible blood types
Human Blood Groups
 A gene has multiple phenotypic effects
 The wide-ranging symptoms of cystic
  fibrosis & sickle-cell disease are due to
  a single gene
Extending Mendelian Genetics
 for Two or More Genes
   Some traits may be determined by
    two or more genes
   Epistasis
   Polygenic inheritance
   A gene at one locus alters the phenotypic
    expression of a gene at a second locus
   In mice and many other mammals, coat color
    depends on two genes.
   One, the epistatic gene, determines whether
    pigment will be deposited in hair or not.
       Presence (C) is dominant to absence (c).
   The second determines whether the pigment
    to be deposited is black (B) or brown (b).
       The black allele is dominant to the brown allele.
   An individual that is cc has a white (albino)
    coat regardless of the genotype of the
    second gene.
   A cross between two
    black mice that are
    heterozygous (BbCc)
    will follow the law of
   However, unlike the
    9:3:3:1 offspring ratio
    of an normal Mendelian
    experiment, the ratio is
    nine black, three
    and four white.
Polygenic Inheritance
   Many human characters the additive
    effects of two or more genes on a single
    phenotypic character.
   For example, skin color in humans is controlled
    by at least three different genes.
       Each gene has two alleles, one light and one dark,
        that demonstrate incomplete dominance.
       An AABBCC individual is dark and aabbcc is light.
   Vary in the population along a continuum and
    are called quantitative characters Do not
    fit the either-or basis that Mendel studied
An additive effect of two or more genes
on a single phenotype
Nature and Nurture
Mendelian Inheritance in Humans

   Humans are not convenient subjects for
    genetic research
     However,  the study of human genetics
      continues to advance
Pedigree Analysis
   Is a family tree that describes the
    interrelationships of parents and
    children across generations
     Can also be used to make predictions about
      future offspring
Pedigree Analysis
Recessively Inherited Disorders
   Many genetic disorders are inherited in a recessive
   These range from the relatively mild (albinism) to
    life-threatening (cystic fibrosis).
   The recessive behavior of the alleles occurs because
    the allele codes for either a malfunctioning protein or
    no protein at all.
       Heterozygotes have a normal phenotype because one
        ―normal‖ allele produces enough of the required protein.
       Individuals who lack the disorder are either homozgyous
        dominant or heterozygotes.
       heterozygotes no clear phenotypic effects carriers
        who may transmit a recessive allele to their offspring.
       heterozygotes may have no clear phenotypic effects, they
        are carriers who may transmit a recessive allele to their
Cystic Fibrosis
   Caucasians, 1in 25 are carriers
   Symptoms of cystic fibrosis include
     Mucus buildup in the some internal organs
     Abnormal absorption of nutrients in the
      small intestine
   Treatment
     untreated  death by the age of 5
     Treated  live to 30yrs antibiotics
      forced mucus discharge
     Gene therapy/?
Sickle-Cell Disease
   Sickle-cell disease
     Affects one out of 400 African-Americans
     Is caused by the substitution of a single
      amino acid in the hemoglobin protein in red
      blood cells
   Symptoms include
       Physical weakness, pain, organ damage, and
        even paralysis
Mating of Close Relatives

   Matings between relatives
     Can increase the probability of the
      appearance of a genetic disease
     Are called consanguineous matings
Prevalence of CF, SC & TS
 Exist b/c they have benefits
 Sickle Cell 1 recessive gene gives
  protection against malaria
 Tay Sachs prevention from
 Cyctic Fibrosis protection against
  cholera/diarrhea driven diseases
Dominantly Inherited
   Some human disorders
       Are due to dominant
   Achondroplasia a
    form of dwarfism that
    is lethal when
    homozygous for the
    dominant allele
                          Figure 14.15
Huntington’s Disease
   A degenerative disease of the nervous system
   Has no obvious phenotypic effects until about
    35 to 40 years of age
   Any child born to a parent who has the allele
    for Huntington’s disease has a 50% chance of
    inheriting the disease and the disorder.
   Molecular geneticists have used pedigree
    analysis of affected families to track down
    the Huntington’s allele to a locus near the tip
    of chromosomes 4.
Pedigree Analysis tracking
Multifactorial Disorders

   Many human diseases
       Have both genetic and environment
   Examples
     Heart disease
     Cancer
Genetic Testing and
   Genetic counselors
       Can provide information to prospective
        parents concerned about a family history
        for a specific disease
Counseling Based on Mendelian
Genetics and Probability Rules
   Using family histories
       Genetic counselors help couples determine
        the odds that their children will have
        genetic disorders
Tests for Identifying Carriers
   For a growing number of diseases
       Tests are available that identify carriers
        and help define the odds more accurately
   The liquid that bathes the fetus is
    removed and tested
Chorionic Villus Sampling (CVS)
   A sample of the placenta is removed and
    Newborn Screening
   Some genetic disorders can be detected at
       By simple tests that are now routinely performed in
        most hospitals in the United States
   Phenyketonuria (PKU) test can detect the
    presence of a recessively inherited disorder,
     This disorder occurs in one in 10,000 to 15,000
     Individuals accumulate the amino acid
      phenylalanine and its derivative phenypyruvate in
      the blood to toxic levels.
     This leads to mental retardation.
     If the disorder is detected, a special diet low in
      phenyalalanine usually promotes normal

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