Turn in HW2 to your TAs folder up front'

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Turn in HW2 to your TAs folder up front.
Black coat color in North American wolves is due
to natural selection for an allele introduced by
hybridization with domesticated dogs (Anderson et
al., Science Express 2/5/09).
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TODAY...

• Extensions of Mendelian inheritance
• Goal understand the diversity of
• genotype gtphenotype relationships
• Pedigree analysis
• Goal recognize and predict pedigrees for four
  common patterns of trait inheritance

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Extensions of Mendelian analysis
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Gene action at single loci Many traits dont
show simple dominance of one allele over one
other

• Incomplete dominance
• Codominance
• Allelic series

Genes segregate exactly as before, but traits do
not.
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(b)
(a)
(c)
(a) Male 1 (b) Male 2 (c) Male 1 or 2 (d) Neither
male 1 or 2 can be the father
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Pleiotropy occurs when one gene affects multiple
traits.
Both traits depend on a single gene that controls
production of a purple pigment, anthocyanin.
Aa or AA
aa
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A special case of pleiotropy Lethal genotypes
agouti (gray)
yellow
x
yy
Yy
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F1
F1
yellow
yellow
x
Yy
Yy
YY
Yy
F2
yy
Yy
2 1
Expected phenotypic ratio gt 3 yellow 1 agouti
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F1
F1
yellow
yellow
x
Yy
Yy
F2
2 1
Actual ratio gt
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Y is lethal as homozygote YY embryos die before
birth
F1
F1
yellow
yellow
x
Yy
Yy
YY
Yy
F2
yy
Yy
2 1
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Extensions of Mendelian analysis
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Multiple loci
Sometimes gene products from different loci act
additively to produce a continuous range of
phenotypes.
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Multiple loci Sometimes gene products from
different loci may interact with each other to
produce unexpected results. Epistasis occurs when
the phenotypic expression of one gene is affected
by the action of another gene.
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White and purple flowers in the sweet pea.
white x white all purple progeny
????????
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Genotype CC or Cc Genotype PP or Pp
Enzyme
Enzyme
Precursor Intermediate
Anthocyanin
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Genotype cc Genotype PP or Pp
Enzyme
No Enzyme
Precursor Intermediate
Anthocyanin
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Genotype CC or Cc Genotype pp
Enzyme
No Enzyme
Precursor Intermediate
Anthocyanin
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Gametes CP Cp cP cp
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Extensions of Mendelian analysis
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• Genes environment Expression variation
• Incomplete penetrance - sometimes the trait
  predicted by a genotype just does not occur (ex.
  dominant polydactly)
• Variable expressivity - sometimes traits are
  expressed to different degrees (ex. disease risk)
• Both of these phenomena probably reflect complex
  interactions of genes with other genes and the
  environment

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Genes environment Temperature-dependence
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Sex-influenced trait pattern baldness
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Dominant in males and recessive in females.

Phenotype Genotype Males
Females BB bald
bald Bb bald
normal bb normal
normal
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Today... Pedigree analysis

• In humans and many animals, pedigree analysis is
  an important tool for studying inherited diseases
  and other traits
• Pedigree analysis 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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Pedigree analysis

• How to read pedigrees
• Basic patterns of inheritance
• autosomal, recessive
• autosomal, dominant
• X-linked, recessive
• X-linked, dominant (very rare)
• Applying pedigree analysis - practice

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Sample pedigree - cystic fibrosis
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Autosomal recessive traits

• Trait is rare in pedigree
• Trait often skips generations (hidden in
  heterozygous carriers)
• Trait affects males and females equally

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Autosomal recessive diseases in humans

• Most common ones
• Cystic fibrosis
• Sickle cell anemia
• Phenylketonuria (PKU)
• Tay-Sachs disease
• For each of these, overdominance (heterozygote
  superiority) has been suggested as a factor in
  maintaining the disease alleles at high frequency
  in some populations

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Autosomal dominant pedigrees

• Trait is common in the pedigree
• Trait is found in every generation
• Affected individuals transmit the trait to 1/2
  of their children (regardless of sex)

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Autosomal dominant traits

• There are relatively few autosomal dominant human
  diseases, but many non-disease traits have this
  inheritance pattern

ex. achondroplasia (a sketelal disorder causing
dwarfism)
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X-linked recessive pedigrees

• Trait is rare in pedigree
• Trait skips generations
• Affected fathers DO NOT pass to their sons
• Males are more often affected than females

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X-linked recessive traits
ex. Hemophilia in European royalty
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X-linked recessive traits

• ex. Glucose-6-Phosphate Dehydrogenase (G6PD)
  deficiency

• hemolytic disorder causes jaundice in infants and
  (often fatal) sensitivity to fava beans in adults
  
• the most common enzyme disorder worldwide,
  especially in those of Mediterranean ancestry
• may confer malaria resistance

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X-linked recessive traits
ex. Glucose-6-Phosphate Dehydrogenase deficiency
Scenario My son is born severely jaundiced. My
father is of Mediterranean ancestry, my mother is
not. Imagine you are the pediatrician.
What would you ask to rule out G6PD deficiency as
a possible cause of the jaundice?
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Can your dad eat fava beans?
XX
X-Y
dad
X-X
me
X-Y
son
For me to have passed X-linked G6PD deficiency to
my son, I would have to have gotten the defective
allele (X-) from my (Mediterranean) dad, and he
would also show the trait.
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X-linked dominant pedigrees

• Trait is common in pedigree
• Affected fathers pass to ALL of their daughters
• Males and females are equally likely to be
  affected

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X-linked dominant diseases

• X-linked dominant diseases are extremely unusual
• Often, they are lethal (before birth) in males
  and only seen in females
• ex. incontinentia pigmenti (skin lesions)
• ex. X-linked rickets (bone lesions)

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Coat color in a wolf pedigree
Black coat color is a) X-linked, dominant b)
X-linked, recessive c) autosomal, dominant d)
autosomal, recessive e) cant tell with info
provided
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Pedigree Analysis in real life

• Remember
• dominant traits may be rare in population
• recessive traits may be common in population
• alleles may come into the pedigree from 2
  sources
• mutation happens
• often traits are more complex
• affected by environment other genes

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Strategy for interpreting pedigrees systematical
ly rule out each of the options
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Based on this pedigree, how is cystic fibrosis
inherited? (a) Autosomal dominant (b) Autosomal
recessive (c) X-linked dominant (d) X-linked
recessive
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Based on this pedigree, how is cystic fibrosis
inherited? (a) Autosomal dominant (b) Autosomal
recessive (c) X-linked dominant (d) X-linked
recessive
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Based on this pedigree, how is this trait
inherited? (a) Autosomal dominant (b) Autosomal
recessive (c) X-linked dominant (d) X-linked
recessive (e) Cant tell with info provided.
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Based on this pedigree, how is this trait
inherited? (a) Autosomal dominant (b) Autosomal
recessive (c) X-linked dominant (d) X-linked
recessive (e) Cant tell with info provided.
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Based on this pedigree, how is this trait
inherited? (a) Autosomal dominant (b) Autosomal
recessive (c) X-linked dominant (d) X-linked
recessive (e) Cant tell with information
provided.
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Based on this pedigree, how is this trait
inherited? (a) Autosomal dominant (b) Autosomal
recessive (c) X-linked dominant (d) X-linked
recessive (e) Cant tell with information
provided.
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Based on this pedigree, how is this trait
inherited? (a) Autosomal dominant (b) Autosomal
recessive (c) X-linked dominant (d) X-linked
recessive (e) Cant tell with information
provided.
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Based on this pedigree, how is this trait
inherited? (a) Autosomal dominant (b) Autosomal
recessive (c) X-linked dominant (d) X-linked
recessive (e) Cant tell with information
provided.
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Pedigree Analysis in real life complications
Sex-limited expression gt trait only found in
males OR females