Inheritance

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InheritanceMendelian Genetics
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Gregor Mendel

• Modern genetics began in the mid-1800s in an
  abbey garden, where a monk named Gregor Mendel
  documented inheritance in peas
• used experimental method
• used quantitative analysis
• collected data counted them
• Most traits in most species do not follow the
  simple Mendelian pattern, but it was a starting
  point

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Mendels work
Pollen transferred from white flower to stigma of
purple flower

• Bred pea plants
• cross-pollinate true breeding parents (P)
• P parental
• raised seed then observed traits (F1)
• F filial
• allowed offspring to self-pollinate observed
  next generation (F2)

P
anthers removed
all purple flowers result
F1
self-pollinate
F2
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What did Mendels findings mean?

• Traits come in alternative versions
• purple vs. white flower color
• alleles
• different alleles vary in the sequence of
  nucleotides at the specific locus (locus
  location on a chromosome) of a gene
• some difference in sequence of A, T, C, G

purple-flower allele white-flower allele are
two DNA variations at flower-color locus
different versions of gene at same location on
homologous chromosomes
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Traits are inherited as discrete units

• For each characteristic, an organism inherits 2
  alleles, 1 from each parent
• diploid organism
• inherits 2 sets of chromosomes, 1 from each
  parent
• homologous chromosomes - same genetic loci (i.e.
  same genes), different alleles at those loci

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What did Mendels findings mean?

• Some traits mask others
• purple white flower colors are separate traits
  that do not blend
• purple x white ? light purple
• purple masked white
• dominant allele
• functional protein
• masks other alleles
• recessive allele
• allele typically makes a malfunctioning protein

mutantallele producingmalfunctioningprotein
wild typeallele producingfunctional protein
homologouschromosomes
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Genotype vs. phenotype

• Difference between how an organism looks its
  genetics
• phenotype
• description of an organisms trait
• the physical, the result of gene expression
• genotype
• description of an organisms genetic makeup
• Its combo of alleles, like Pp

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Dominant ? most common allele

• Because an allele is dominant does not mean
• it is more common, healthier, stronger, better,
  more likely, etc.

Polydactyly dominant allele, yet rare!
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Making crosses

• Can represent alleles as letters
• flower color alleles ? P or p
• true-breeding purple-flower peas ? genotype PP
• true-breeding white-flower peas ? genotype pp
• In research, alleles are usually
  letter/number/symbol combinations (like ser83psE)

Pp
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Discussion

• Which of these are phenotypes and which are
  genotypes?
• 1. Curly hair
• 2. Jj
• 3. PE1PE2
• 4. Arthritic knees
• 5. Type B blood
• 6. Spotted fur and a pink nose
• 7. HHGg
• 8. Purple leaves and spiny stem

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Punnett Square reminders

• The side and top boxes parents potential
  gametes, each equally likely.
• Inner boxes potential zygotes.
• Punnett Squares predict the odds of each
  offspring being born with a given
  genotype/phenotype.
• Does not ensure that, say, 50 of the children
  will definitely be freckled.

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Genotypes

• Homozygous same alleles PP, pp
• True-breeding homozygous
• Heterozygous different alleles Pp
• Carrier

homozygousdominant
heterozygous
homozygousrecessive
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Test cross

• Method to determine genotype in case of dominant
  phenotype
• Breed the dominant phenotype with a homozygous
  recessive (pp) to determine the identity of the
  unknown allele

How does that work?
is itPP or Pp?
pp
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Discussion

• Suppose that the Y allele codes for orange fins
  and the y allele codes for yellow fins.
• The heterozygous genotype __
• The homozygous dominant genotype __
• The homozygous recessive genotype __
• A fish with yellow fins must have a _____________
  genotype.
• A fish with orange fins could be either
  _____________ or ___________________.
• If a fish has orange fins, test-crossing it with
  a ______-finned fish will produce either 100
  _____ or 50 orange/50 yellow. If the former
  result, the orange fish was _________. If the
  latter result, the orange fish was _________.

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Mendels 1st law of heredity

• Law of segregation
• during meiosis, alleles segregate
• homologous chromosomes separate
• each allele for a trait is packaged into a
  separate gamete
• You only give 1 allele per gene to your child

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Law of Segregation

• Suppose theres an eye color locus, with the
  alleles B for brown eyes or b for blue eyes.
• A man has the genotype Bb, which gives him the
  phenotype brown eyes.
• Meiosis produces his gametes

b
He can make gametes that are EITHER B or b. Half
of his gametes will be one, half will be the
other. Thats segregation!
b
b
S Phase
b
b
b
b
Meiosis I
B
Meiosis II
B
B
B
Normal cell in G1
B
B
B
Four Gametes
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Discussion

• Monohybrid cross practice! Show Punnett Squares
  to support your answer.
• If two black bees (bees A and B) have 676 babies,
  all black two red bees (bees C and D) have 983
  babies, all red and a different two black bees
  (bees E and F) have 524 babies, 220 red and 304
  black, what was each bees genotype? Use any
  letter for the alleles that you want.
• What generation were bees A,B,C,D,E, and F a part
  of? What generation were their children a part
  of?

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Dihybrid cross

• Other of Mendels experiments followed the
  inheritance of 2 different characters
• seed color and seed shape
• dihybrid crosses

Mendelwas working outmany of the genetic rules!
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Dihybrid cross
P
true-breeding yellow, round peas
true-breeding green, wrinkled peas
x
YYRR
yyrr
Y yellow R round
y green r wrinkled
YyRr
self-pollinate
9331
9/16 yellow round peas
3/16 green round peas
3/16 yellow wrinkled peas
1/16 green wrinkled peas
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Dihybrid cross
or
YyRr
YyRr
x
YR
Yr
yR
yr




YYRR
YYRr
YyRR
YyRr
YYRr
YYrr
YyRr
Yyrr
YyRR
YyRr
yyRR
yyRr
YyRr
Yyrr
yyRr
yyrr
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Mendels 2nd law of heredity

• Law of independent assortment
• different loci (genes) separate into gametes
  independently
• non-homologous chromosomes align independently
• classes of gametes produced in equal amounts
• YR Yr yR yr

YyRr
Yr
Yr
yR
yR
YR
YR
yr
yr

1
1

1

1
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Discussion

• Complete a Punnett Square for this dihybrid cross
  problem!
• If A tall and a short, while B fuzzy and b
  smooth
• What are the odds that a parent heterozygous for
  both traits and a short smooth parent will have a
  tall and fuzzy offspring?

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Law of Independent Assortment

• EXCEPTION
• If genes are on same chromosome close together
• will usually be inherited together
• rarely crossover separately
• linked

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Rules of Probability

• Probability scale ranges from 0 to 1
• Rule of Multiplication determine the chance that
  two or more independent events will occur
  together in some specific combination.
• Compute the probability of each independent
  event.
• Then, multiply the individual probabilities to
  obtain the overall probability of these events
  occurring together.
• Rule of Addition probability of an event that
  can occur two or more different ways is the sum
  of the separate probabilities of those ways.

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Rules of Probability

• For instance, if I roll a six-sided die, what are
  the odds Ill get a number that is equal to or
  less than 2? Which law did you use?
• If I roll two dice, what are the odds Ill get a
  1 both times? Which law did you use?

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Discussion

• You have been using both rules all along!
• How does the rule of multiplication come into
  play in a monohybrid cross?
• The rule of addition?

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Rules of Probability

• What are the odds that a homozygous red-haired,
  heterozygous green-eyed, white-chinned cat
  (AAEeww) and a dark-haired, heterozygous
  green-eyed, white-chinned cat (aaEeww) would have
  a kitten with the genotype AaEeww?
• We can solve each gene as a separate monohybrid
  problem, then multiply!

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Discussion

• AAEeww x aaEeww ? AaEeww

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Discussion

• Determine the probability of finding two
  recessive phenotypes for at least two of three
  traits resulting from a trihybrid cross between
  pea plants that are PpYyRr and Ppyyrr.
• There are five possible genotypes that fulfill
  this condition ppyyRr, ppYyrr, Ppyyrr, PPyyrr,
  and ppyyrr.
• Hint Use the rule of multiplication to calculate
  the probability for each of these genotypes, and
  then use the rule of addition to pool the five
  probabilities.

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Answer

• The probability of producing a ppyyRr offspring
• The probability of producing pp 1/2 x 1/2
  1/4.
• The probability of producing yy 1/2 x 1 1/2.
• The probability of producing Rr 1/2 x 1 1/2.
• Therefore, the probability of all three being
  present (ppyyRr) in one offspring is 1/4 x 1/2 x
  1/2 1/16.
• For ppYyrr 1/4 x 1/2 x 1/2 1/16.
• For Ppyyrr 1/2 x 1/2 x 1/2 2/16
• For PPyyrr 1/4 x 1/2 x 1/2 1/16
• For ppyyrr 1/4 x 1/2 x 1/2 1/16
• Therefore, the chance of at least two recessive
  traits is 6/16 3/8.

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Beyond Mendels Lawsof Inheritance
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Mendel chose peas luckily

• Relatively simple genetically
• most characters are controlled by a single gene
  with each gene having only 2 alleles
• one completely dominant over the other
• All the genes he chose happened to be on
• different chromosomes - whew!

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Extending Mendelian genetics

• The inheritance of traits can rarely be explained
  by simple Mendelian genetics
• Various patterns of inheritance incomplete
  dominance, codominance, pleiotropy, lethality,
  epistasis, polygenetic traits, multiallelic
  genes, sex-linked traits
• Not all traits just determined by nuclear DNA
  environmental effects, gene regulation,
  mitochondrial DNA

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Incomplete dominance

• Heterozygote shows a NOVEL, intermediate, blended
  phenotype
• example
• RR red flowers
• rr white flowers
• Rr pink flowers
• make 50 less color

?RR
?WW
?RW
RR
WW
RW
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Incomplete dominance
X
true-breeding red flowers
true-breeding white flowers
P
self-pollinate
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Co-dominance

• 2 alleles affect the phenotype equally
  separately
• Phenotype is not blended, its both of the
  true-breeding phenotypes simultaneously
• Speckled chickens, Roan cows, human ABO blood
  groups
• 3 alleles
• IA, IB, i
• IA IB alleles are co-dominant
• glycoprotein antigens on RBC
• IAIB both antigens are produced
• i allele recessive to both

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Genetics of Blood type
pheno-type genotype antigenon RBC antibodiesin blood donationstatus
A IA IA or IA i type A antigenson surface of RBC anti-B antibodies __
B IB IB or IB i type B antigenson surface of RBC anti-A antibodies __
AB IA IB both type A type B antigens on surface of RBC no antibodies universal recipient
O i i no antigens on surface of RBC anti-A anti-B antibodies universal donor
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Pleiotropy

• Most genes are pleiotropic
• one gene affects more than one trait
• dwarfism (achondroplasia)

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Lethal pleiotropy
Aa x aa
Aa x Aa
dominantinheritance
a
a
A
a




Aa
Aa
AA
Aa
A
A
achondroplastic
lethal
achondroplastic
achondroplastic
a
a
aa
aa
aa
Aa
typical
achondroplastic
typical
typical
50 affected50 typical or 11
67 affected33 typical or 21
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Discussion

• What if an allele is lethal recessive?
• Suppose that in a plant, the recessive allele for
  yellow seeds is lethal, the dominant allele for
  green seeds is not.
• What phenotypic ratios would you get from a cross
  of
• GG x Gg?
• Gg x Gg?
• Gg x gg? (gg produced by genetically engineering
  gametes while leaving the somatic cells intact)

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Epistasis

• One gene completely masks another gene
• coat color in mice 2 separate genes
• C,c pigment (C) or no pigment (c)
• B,b more pigment (blackB) or less (brownb)
• cc albino, no matter B allele
• 9331 becomes 934

B_C_
B_C_
bbC_
bbC_
_ _cc
_ _cc
How would you know thatdifference wasnt random
chance? Chi-square test!
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Epistasis in Labrador retrievers

• 2 genes (E,e) (B,b)
• pigment (E) or no pigment (e)
• pigment concentration black (B) to brown (b)

EB
Ebb
eeB
eebb
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Polygenic inheritance

• Some traits determined by additive effects of 2
  or more genes
• phenotypes on a continuum
• human traits
• skin color
• height
• weight
• intelligence
• behaviors

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Skin color Albinism

• However, albinism can be inherited as a single
  gene trait
• aa albino

enzyme
tyrosine
melanin
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Sex linked traits

• Genes are on sex chromosomes
• as opposed to autosomal chromosomes
• first discovered by T.H. Morgans Fly Lab at
  Columbia U.
• Drosophila breeding
• good genetic subject
• prolific
• 2 week generations
• 4 pairs of chromosomes
• XXfemale, XYmale

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Classes of chromosomes
autosomalchromosomes
sexchromosomes
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Discovery of sex linkage
true-breeding white-eye male
true-breeding red-eye female
X
P
Huh!Sex matters?!
100 red eye offspring
F1 generation (hybrids)
100 red-eye female
50 red-eye male 50 white eye male
F2 generation
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Genetics of Sex

• In humans other mammals, there are 2 sex
  chromosomes X Y
• 2 X chromosomes
• develop as a female XX
• gene redundancy,like autosomal chromosomes
• an X Y chromosome
• develop as a male XY
• no redundancy

X
Y


X
XX
XY
X
XY
XX
50 female 50 male
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Lets reconsider Morgans flies
P
x
x
F1
XRXR
XrY
XRXr
XRY
F2
Xr
Y
XR
Y




XR
XR
XRY
XRXr
XRY
XRXR
BINGO!
F1
XR
Xr
XRXr
XRY
XRXr
XrY
100 red females 50 red males 50 white males
100 red eyes
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Genes on sex chromosomes

• Y chromosome
• few genes other than SRY
• sex-determining region
• master regulator for maleness
• turns on genes for production of male hormones
• many effects pleiotropy!
• X chromosome
• other genes/traits beyond sex determination
• mutations
• hemophilia
• Duchenne muscular dystrophy
• color-blindness

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Human X chromosome

• Sex-linked
• usually meansX-linked
• more than 60 diseases traced to genes on X
  chromosome

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(No Transcript)
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Discussion

• Hemophilia is X-linked recessive. If a carrier
  and her healthy (unaffected) husband have a
  child, what are the odds that their child will
  be
• Healthy?
• Hemophiliac?
• A carrier?

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X-inactivation

• Female mammals inherit 2 X chromosomes
• one X becomes inactivated during embryonic
  development
• condenses into compact object Barr body
• which X becomes Barr body is random
• patchwork trait mosaic

patches of black
tricolor catscan only befemale
patches of orange
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Male pattern baldness

• Sex influenced trait
• autosomal trait influenced by sex hormones
• age effect as well onset after 30 years old
• dominant in males recessive in females
• B_ bald in males bb bald in females

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Environmental effects

• Phenotype is controlled by both environment
  genes

Human skin color is influenced by both genetics
environmental conditions
Coat color in arctic fox influenced by heat
sensitive alleles
Color of Hydrangea flowers is influenced by soil
pH
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Pedigrees
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Pedigree analysis

• Pedigree analysis reveals Mendelian patterns in
  human inheritance
• data mapped on a family tree

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Studying Human Genetics

• Circle female
• Square male
• Shaded afflicted with trait
• Half shaded or Dot
• carrier
• Horizontal line
• mating marriage line
• sibling line
• Vertical line children
• Dotted vertical line - adopted children
• (Diagonal lines twins)

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Discussion

• Draw a pedigree of your immediate family (if
  adopted, draw your choice of relatives)

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Pedigrees

• Pedigree analysis can reveal the inheritance
  pattern of the trait under consideration

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Autosomal Dominant

• Autosomal dominant allele is dominant and on an
  autosomal chromosome
• Every person with the trait, also had a parent
  with it.
• Not necessarily a child with it, though! Why?

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Autosomal Recessive

• Autosomal Recessive - allele is recessive and on
  an autosomal chromosome
• Trait only appears when two alleles are present,
  so there can be carriers.
• Trait often skips several generations or shows
  up seemingly out of nowhere. Why?

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X-linked Recessive

• X-linked Recessive allele is recessive and is
  located on the X chromosome
• Males are more likely to show trait Why?
• Skips generations

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X-linked Dominant

• X-linked Dominant - allele is dominant and is
  located on the X chromosome
• An afflicted fathers daughters will all be
  afflicted too Why?
• No male to male transmission
• No skipped generations

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Y-Linked

• Y-Linked (recessive vs dominant doesnt matter)
  Locus is on the Y chromosome
• Only males have it, and all sons of an affected
  male are also affected Why?

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Discussion
Whats the likely inheritancepattern? Label
genotypes using A/a
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Genetic counseling

• Pedigree can help us understand the past
  predict the future
• Thousands of genetic disorders are inherited as
  simple recessive traits
• from benign conditions to deadly diseases
• albinism
• cystic fibrosis
• Tay sachs
• sickle cell anemia
• PKU

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Genetic testing
sequence individual genes
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Tay-Sachs (recessive)

• Great example of how pedigrees and genetic
  counseling have made a difference!
• Primarily Jews of eastern European (Ashkenazi)
  descent Cajuns (Louisiana)
• strikes 1 in 3600 births
• 100 times greater than incidence among non-Jews
• non-functional enzyme fails to breakdown lipids
  in brain cells
• fats collect in cells destroying their
• function
• symptoms begin few months after birth
• seizures, blindness degeneration of muscle
  mental performance
• child usually dies before age 5

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Tay-Sachs

• Israel became the 1st country to offer free
  genetic testing to couples, in large part to
  eliminate TSD
• Haredi communities in the US often required
  couples to be tested before marriage
• Incidence of TSD declined by 90!
• Before 1970, 50-70 Ashkenazi infants born with
  TSD per year in US
• By 2000s, only 1 or 2 per decade

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Non-Nuclear Inheritance

• Not all eukaryotic genes are in the nucleus!
• Found in mitochondria, plastids
• In animals, all cytoplasmic (non-nuclear) genes
  come from which parent, maternal or paternal?
• Randomly assorted to gametes and daughter cells
• Therefore, traits determined by plastid DNA and
  mtDNA do NOT display Mendelian inheritance

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Non-Nuclear Inheritance

• In humans, mitochondrial DNA (mtDNA) encodes
  mostly mitochondrial proteins (such as ETC
  proteins, mt-ribosomes)
• Mutations cause mitochondrial disorders,
  including lactic acidosis, some myopathies
  (muscle disorders)