Outline of major topics

							           Outline of major topics


• Allelic actions and interactions
  • Dominance
      • how it works
          • when there is no real dominance
  • Multiple alleles
  • Lethal alleles
         Outline of major topics ...


• Genic interactions
  • Metabolic pathways
     • novel phenotypes
     • epistasis
     • (pleiotropy)
         Outline of major topics ...


• Factors affecting phenotype
  • Genetic factors
     • Strange genes
  • Environmental factors
         Allelic actions: dominance


• In general, dominant allele codes for
  production of functional protein
  • P --> purple pigment
• In general, recessive allele codes for no
  functional protein
  • p --> no pigment
      Allelic actions: dominance ...


PP has two alleles coding for purple pigment

Pp has one allele coding for purple pigment, one
allele coding for nothing

pp has no alleles coding for pigment
       Allelic actions: dominance ...


• In many cases, a simple dominant/recessive
  relationship does not hold
  • incomplete or co-dominance
       Incomplete or Co-dominance


• If both alleles code for a contrasting
  functional protein, heterozygote shows a
  phenotype completely different from either
  homozygote!

• Two different upper case letters used to
  symbolize the alleles or one letter w/
  superscripts
     Incomplete or Co-dominance ...


• Flower color in carnations
   • R codes for a red pigment
   • W codes for a white pigment
      • RR gives a red flower
      • WW gives a white flower
      • RW gives a pink flower
     Incomplete or Co-dominance ...

Phenotypic ratios = genotypic ratios

Pink X Pink --> 1/4 Red, 1/2 Pink, 1/4 White

                R        W
         R      RR      RW

         W     RW      WW
     Incomplete or Co-dominance ...

Andalusian fowl:

   black X black --> black
   white X white --> white
   black X white --> gray (blue)
   gray X gray     --> ?
     Incomplete or Co-dominance ...


• heterozygote shows a BLEND: alleles are
  incompletely dominant


• heterozygote shows BOTH: alleles are co-
  dominant
    Incomplete or Co-dominance ...

MN Blood grouping (Landsteiner and Levine)

  two alleles:

  M - produces M antigens

  N - produces N antigens
         Incomplete or Co-dominance ...

Genotypes:     Phenotypes:

                                                M
   MM        Type M; has only M antigens    M
                                                    M

                 (Anti-N antibodies)             M


                                           M N
   MN        Type MN; has both antigens
                 (no antibodies)           N M


                                               N
   NN        Type N; has only N antigens     N
                                              N N
                 (Anti-M antibodies)
     Incomplete or Co-dominance ...


• Incomplete dominance = co-dominance
• Just label differently depending on whether
  phenotype shows BLENDING
• Mechanism generally the same; both alleles
  code for a working protein
               Multiple alleles


• May be > just two choices of alleles at one
  locus
• Population level phenomenon; individuals
  have, at most, two different alleles
  (heterozygous)
            Multiple alleles ...

ABO Blood Groupings


Four possible blood types (phenotypes):

     A      B       AB        O



Controlled by one gene
         ABO Blood Groupings ...

Three alleles, with co-dominance as well as
as dominant/recessive relationship

Alleles: A, B, O
      (or IA IB IO)

Phenotype (blood type) is a result of the proteins
coded for by each allele
         ABO Blood Groupings ...


A codes for A antigen
B codes for B antigen
O codes for no antigen
          ABO Blood Groupings ...
AA
     Type A: A antigens; anti-B antibodies
AO
BB
   Type B: B antigens; anti-A antibodies
BO
AB   Type AB: A & B antigens; no antibodies

OO Type O: no antigens; anti-A and
   anti-B antibodies
         ABO Blood Groupings ...


• O is recessive to both A and B
• A and B are co-dominant
• Blood type AB is considered the “universal
  recipient”
   • no antibodies produced
• Blood type O is considered the “universal
  donor”
   • no antigens produced
                Reminders ...


• Dominance is not an inherent property of an
  allele
• An allele may be dominant to a second allele,
  but co-dominant, incompletely dominant, or
  even recessive to a third
Coat color in rabbits


Four alleles:
  c+            cch        ch          ca

 agouti    chinchilla   Himalayan    albino

c+ is dominant to all others
cch is incompletely dominant to ch and ca
ch is dominant to ca
           Coat color in rabbits ...

c+ __                   agouti

cch cch                 chinchilla

cch ca                  light gray

cch ch                  light gray w/dark tips

ch ch or chca           Himalayan

c a ca                  albino
             Multiple alleles ...


• Many, if not most, genes do have multiple
  possible alleles
   • Rhesus blood group (+ or -)
      • actually at least 18 alleles
   • One white eye locus in Drosophila
      • over 100 alleles
                 Lethal alleles


• First described by Cuenot in 1905
  • coat color in mice
     • strain with yellow coats
         • yellow dominant to wild-type agouti
         • could not produce true-breeding
           (homozygous) yellows
              Lethal alleles ...


• Each time Cuenot crossed two yellow mice,
  1/3 of the offspring were agouti
• Backcrossed yellow mice to agouti, saw all
  yellow mice were heterozygotes
  • Impossible to produce homozygous yellow
    mice!
               Lethal alleles ...

• Castle and Little offered explanation:
  • yellow allele dominant w/ respect to coat
    color
  • yellow allele also a recessive lethal allele
     • homozygous yellows die as embryos
                Lethal alleles ...

Yellow X Yellow
 cy c+        cy c+

         c+     cy        cycy do not live to birth
                          Apparent ratio:
 c+   c+c+     cyc+       2/3 yellow : 1/3 agouti

 cy   cyc+     cycy
                  Lethal alleles ...

• Mechanisms of lethality
  • recessive lethals: not coding for some
    necessary product

  • Hemophilia: dominant allele --> clotting factor
                  recessive allele -> no clotting factor

  • Sickle cell anemia: S --> normal hemoglobin
                           s --> abnormal hemoglobin
               Lethal alleles ...

• Mechanisms of lethality …

  • Dominant lethals: very rare. Gene product
    itself causes death

  • Huntington’s disease: H --> type of neurotoxin
                            h --> no neurotoxin

  • Retinoblastoma: R --> allows tumor formation
                      r --> no tumor formation
               Lethal alleles ...


• Once again, note that “dominance” in itself
  means nothing.
  • Refers only to phenotype that appears in
    the heterozygote
     • Lethals may be dominant with respect to
       one phenotype and recessive with
       respect to the lethal action
            Genic interactions

• Two or more genes acting on one trait
   • Novel phenotypes
   • Epistasis
• One gene acting on more than one trait
   • Pleiotropy

    ***All due to metabolic pathways***
  Genic interactions: Novel Phenotypes

Eye color in Drosophila

       P:    red eyed     x    white eyed

       F1:              red eyed

       F2:         9      red eyed
                   3      brown eyed
                   3      scarlet eyed
                   1      white eyed
 Genic interactions: Novel Phenotypes

S = wild-type (red)     B = wild-type (red)
s = scarlet             b = brown


     S __   B __      --> wild-type (red)
     S __   bb        --> brown eyes
     ss     B __      --> scarlet eyes
     ss     bb        --> white eyes
    Genic interactions: Novel Phenotypes

The S allele controls the production of BROWN pigment

The B allele controls the production of SCARLET pigment


    Cpd. Y ---enzyme S---> BROWN
                                              RED
  Cpd. X ---enzyme B---> SCARLET
 Genic interactions: Novel Phenotypes

Poultry: comb shape

Two genes, w/ 2 alleles each:
     pea vs. single, and rose vs. single

Considered separately:

AA, Aa = pea                 BB, Bb = rose
    aa = single                  bb = single
    Genic interactions: Novel Phenotypes
              Poultry comb shapes ...

The genotype at each of 2 loci plays a role in
determining comb shape:

                A__ B__ = walnut


                aa B__ = rose


                A__ bb = pea


                aa bb    = single
       Genic interactions: Epistasis


• One gene masks a second gene
• Due to a linear, instead of branched,
  metabolic pathway
Genic interactions: Epistasis
     Coat color in mice

B = agouti       A = non-albino
b = black        a = albino


       A__ B__    = agouti
       A__ bb     = black
       aa __ __ = albino
       Genic interactions: Epistasis
          Coat color in mice ...

Colorless                           black
               enzyme A             pigment
precursor




   enzyme B               agouti
                          pattern
   Genic interactions: Epistasis
      Coat color in mice ...

Aa Bb X Aa Bb:

  9 AB                agouti
  3 Ab                black
  4 (3 aB + 1 ab)     white
    Epistasis: Coat color in Labs

B = black            E = black or chocolate
b = chocolate        e = yellow

     E__ B__    Black
     E__ bb     Chocolate
     ee B __    Yellow
     ee bb      Yellow
    Genic interactions: Epistasis

Fruit color in summer squash

  aa   bb       = green
  aa   B__      = yellow
  A__ __ __ = white


Aa Bb x Aa Bb
 How can we distinguish allelic interactions
        from genic interactions?

• While the F2 ratios will not follow basic Mendelian
  rules, they still provide information
• Allelic interaction (one gene) will lead to a
  deviant 3:1
   • 1:2:1 most likely
• Genic interaction (2 genes) will lead to a deviant
  9:3:3:1
   • 9:3:4 12:3:1         9:6:1    9:7
   • 3 genes: deviant 27:9:9:9:3:3:3:1
                 Pleiotropy


• One gene may affect more than one trait
• This is again due to the metabolic pathways
  involved
                     Pleiotropy

• PKU - phenylketonuria

  • P codes for phenylalanine hydroxylase
     • enzyme metabolizes phenylalanine

  • p does not code for functional enzyme
     • phenylalanine cannot be metabolized

  • primary result: mental retardation

  • also affects head size, skin/hair/eye color, “mousy”
    odor, peculiarities of gait, stance, sitting posture,
    eczema, epilepsy
Pleiotropy: PKU metabolic pathway

  protein


phenylalanine               phenylpyruvic acid (PKU)
         phenylalanine hydroxylase

  tyrosine
             transaminase

  melanin
  Other factors affecting phenotype

• Overview
  • Genetic factors
     • Incomplete penetrance
     • Variable expressivity
     • Sex limited and sex influenced traits
  • Environmental factors
     • Nutrition, light, temperature, etc.....
   Incomplete Penetrance and Variable
              Expressivity

• Incomplete penetrance
   • Identical genotypes differ in phenotype
   • Penetrance = % individuals w/ genotype
     expressing the associated phenotype
• Variable expressivity
   • Variation in the degree of expression of the
     phenotype
         Incomplete Penetrance

Eye shape in Drosophila
  Lobe locus: dominant allele which reduces
      the size of the eye

    LL         Ll         ll

     reduced eye     normal eye
          Incomplete Penetrance

However, only 75% of the flies carrying the
    L allele actually have reduced eyes.

25% of the LL and Ll individuals have eyes which
    appear perfectly normal; just like ll flies.

The penetrance of the lobe allele is said
     to be 75%.
           Variable Expressivity


• Neurofibromatosis - autosomal dominant
  • 1/3 virtually symptom free; presence of
    café-au-lait spots & benign skin tumors
  • 1/3 symptom free most of the time;
    episodes of acute illness
  • 1/3 severely affected; symptoms severe
    enough to cause death
             Sex Limited Traits


• Traits which appear exclusively in one sex
   • All genotypes possible in both sexes
   • One phenotype limited to one sex
• Generally regulated by a hormone level
  threshold
• Any secondary sexual characteristic is sex
  limited
                   Sex Limited Traits
   Horns in some breeds of sheep:

         H+ = production of horns
         H- = no horns

                     H+H+           H+H-           H-H-
       males:        horns          horns        no horns
       females:      no horns       no horns     no horns

There must be a sufficiently high level of testosterone for horns
to be produced. Only males have enough!
                Sex Influenced Traits


 • Sex determines which allele is dominant
   • male and female heterozygotes differ in
     phenotype!
           AA               AB             BB

males:     A                 A             B

females:   A                 B             B
             Sex Influenced Traits
Horns in Suffolk sheep:

                   h+ h+        h+ h-      h- h-
  males:           horns        horns     no horns

  females:         horns       no horns   no horns


Again, related to hormonal thresholds.
               Sex Influenced Traits
Male pattern baldness: Testosterone threshold.

    B = bald                    N = not bald

             BB           BN             NN

males:      bald         bald           not bald

females:    thinning     not bald       not bald
Environmental effects on phenotype

• The environment may greatly influence the
  expression of genotypes
   • light
   • temperature
   • nutrition
   • cosmetics
   • drugs
   Environmental effects on phenotype


• Light
  • Corn: sunred allele - homozygous plants
    bright red when grown in full sun
     • Appear green if all but red light screened
  • Humans: freckles (dominant) - phenotype
    is a combination of presence of allele and
    exposure to sunlight
   Environmental effects on phenotype


• Temperature
   • Primroses: red flowers if reared at room
     temperature; white flowers if >86o F
   • Rabbits (Himalayan allele) & Siamese cats:
     darker extremities due to lower
     temperature
   • Many Drosophila melanogaster wing
     mutations
   Environmental effects on phenotype


• Temperature, continued…
   • Sea turtles: sex is determined by
     temperature at which the egg is incubated
   • Warmer = female; cooler = male
   Environmental effects on phenotype


• Nutrition
  • PKU: reduce protein intake, eliminate
    phenotype
  • Diabetes: reduce sugar intake or provide
    insulin, eliminate or reduce phenotype
  • Significant height increase in first
    generation Americans
   Environmental effects on phenotype


• Drugs
  • Hemophilia: supply blood clotting factor,
    eliminate phenotype
  • Cocaine: may induce schizophrenia
   Environmental effects on phenotype


• Environmental factors may produce mimics of
  genetic traits
   • phenocopies
      • thalidomide
         • 1950s treatment for morning sickness
         • produced phenocopy of phocomelia,
           “paddle limbs”
         • drug in use again for cancer,
           Hansen’s disease (leprosy)
   Environmental effects on phenotype


• May modify effects of genotypes for good or
  bad
• May mask genes or mimic genes
• These phenotypic changes WILL NOT be
  passed on to offspring. Genotype not
  changed, just phenotype.