Linking chromosomes to genetics

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Welcome back to IB 150...
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Lecture 7 Complex Patterns of Inheritance
Assigned Readings Ch. 14, 14.3 to end
By the end of this lecture you should be able
to Identify complex patterns of inheritance not
described by Mendel. degrees of dominance
epistasis pleiotropy environmental
effects.  Give examples of degrees of
dominance. complete dominance incomplete
dominance codominance
 Understand that an allele of one gene can mask
an allele of another gene. epistasis in mouse
coat color Understand that a single allele may
have multiple effects on phenotype. sickle cell
allele Define the norm of reaction. phenotypic
range
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Assessment of dominance depends on the level of
analysis!
A heterozygote may display a dominant phenotype
at the organismal level, but at a biochemical
level may show incomplete dominance.
Tay-Sachs disease caused by absence of an
enzyme, hexosaminidase A (Hex-A)
Homozygous dominant normal levels of Hex-A,
normal development of child Homozygous recessive
no Hex-A, death of child by age
5 Heterozygote1/2 normal levels of Hex-A, normal
development of child
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Assessment of dominance depends on the level of
analysis!
Survival
die
live
Complete Dominance
HexA/ HexA
HexA/ HexA-
HexA-/ HexA-
Tay-Sachs
Amount of hexaminidase
die
live
Incomplete Dominance
HexA-/ HexA-
HexA/ HexA
HexA/ HexA-
Tay-Sachs
HexA- codes for a nonfunctional enzyme.
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Epistasis one gene alters or blocks the
expression of another independently inherited
gene
Disclaimer Made-up example
A mutant gene that caused complete baldness in
humans would be epistatic to a gene that
determines hair color.
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A 9331 ratio is the standard result for a
dihybrid cross
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Epistasis Normal dihybrid ratio is altered from
9331 to 9340
C/c gene is epistatic to the B/b gene
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Color genetics in Cape Primrose - an explanation
for how epistatis works.
Alleles of Gene O that produce nonfunctioning
enzymes (null alleles), if honozygous, stop the
chain at the rose stage.
Enzyme 1
Enzyme 2
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Pleiotropy one gene causes multiple effects on
phenotype
Sickle cell anemia one mutant gene, many symptoms
Single amino acid substitution in the hemoglobin
protein
Pain, stroke, leg ulcers, bone damage, jaundice,
gallstones, lung damage, kidney damage, eye
damage, anemia, delayed growth
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Polygenic inheritance additive effects
(essentially, incomplete dominance) of multiple
genes on a single trait
AA dark Aa less dark aa - light And similarly
for the other two genes - in all cases dominance
is incomplete for each gene. Think of each
capital allele (A, B, C) as adding a dose of
brown paint to white paint.
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• environment often influences phenotype
• the norm of reaction phenotypic range due to
  environmental effects
• norms of reactions are often broadest for
  polygenic characters.

Blue require low pH
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Environmental effects effect of temperature on
pigment expression in Siamese cats
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Lecture 7 Complex Patterns of Inheritance
Assigned Readings Ch. 14, 14.3 to end
By the end of this lecture you should be able
to Identify complex patterns of inheritance not
described by Mendel. degrees of dominance
epistasis pleiotropy environmental
effects.  Give examples of degrees of
dominance. complete dominance incomplete
dominance codominance
 Understand that an allele of one gene can mask
an allele of another gene. epistasis in mouse
coat color Understand that a single allele may
have multiple effects on phenotype. sickle cell
allele Define the norm of reaction. phenotypic
range
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Lecture 8 Mendelian Inheritance in Humans
Readings Ch. 14
Understand the use of pedigree analysis to
determine patterns of inheritance in humans.
inherited disorders genetic diseases.  Name the
5 categories of genetic diseases observed in
humans. single gene disorders multifactorial
(polygenic) traits chromosomal abnormalities
mitochondrial inheritance diseases of unknown
etiology Identify the conventional symbols used
to depict human family trees. pedigree Name the
5 categories of single gene (Mendelian)
disorders. autosomal recessive autosomal
dominant multifactorial, chromosomal, and
mitochondrial, unknown etiology
 Give examples of autosomal recessive traits and
be able to identify the pattern of inheritance.
cystic fibrosis Tay-Sachs sickle cell
disease Give examples of autosomal dominant
traits and be able to identify the pattern of
inheritance. Huntington Disease Give examples of
mitochondrial traits and be able to identify the
pattern of inheritance. Lebers hereditary
optic neuropathy
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Five general categories of genetic disorders exist

• Single gene (Mendelian) disorders
• Polygenic (multifactorial) traits
• Mitochondrial diseases
• Chromosomal abnormalities (Lecture 10)
• Diseases of unknown etiology (causes) that run
  in families

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Five general categories of genetic disorders exist

• Single gene (Mendelian) disorders
• Polygenic (multifactorial) traits
• Mitochondrial diseases
• Chromosomal abnormalities (Lecture 10)
• Diseases of unknown etiology (causes) that run
  in families

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Single gene traits studied using a pedigree
Why do we need to study pedigrees to understand
Mendelian inheritance in humans?
Because The human generation time is about 20
years. Humans produce relatively few offspring
compared to most other species. Well-planned
breeding experiments are impossible.
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Conventional Symbols for Human Pedigrees
Mating
Normal male
Normal female
Normal, sex irrelevant or unknown
Between relatives
Affected male
Affected female
I
Affected, sex irrelevant or unknown
II
Last born
Sibling birth order from left to right
siblings
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Figure 14.14 Pedigree analysis
Widows peak dominant
Attached ear lobe recessive
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Autosomal recessive pedigree examples
Many people in these pedigrees were probably
carriers - heterozygotes
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Genetic diseases to know for IB150

• Tay-Sachs disease single gene, autosomal
  recessive, early lethal, no homozygotes
  reproduce, carriers have normal phenotype
• Sickle cell anemia single gene, autosomal
  recessive, condition can be treated, carriers may
  have symptoms (sickle cell trait)
• Cystic fibrosis single gene, autosomal
  recessive, life can be prolonged, carriers have
  normal phenotype
• Phenylketonuria (PKU) single gene, autosomal
  recessive, can be diagnosed at birth, diet can
  treat, carriers have normal phenotype
• Huntingtons disease single gene, autosomal
  dominant, onset late in life (so patients likely
  to reproduce prior to diagnosis), no carriers
• Heart disease, high blood pressure multiple
  genes, no simple pattern of inheritance, genes
  increase susceptibility
• Lebers hereditary neuropathy mitochondrial,
  relatively late onset, inherited from mother only

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Figure 14.14 Pedigree analysis
Widows peak dominant
Attached ear lobe recessive
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Autosomal dominant pedigree example
No carriers
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Genetic diseases to know for IB150

• Tay-Sachs disease single gene, autosomal
  recessive, early lethal, no homozygotes
  reproduce, carriers have normal phenotype
• Sickle cell anemia single gene, autosomal
  recessive, condition can be treated, carriers may
  have symptoms (sickle cell trait)
• Cystic fibrosis single gene, autosomal
  recessive, life can be prolonged, carriers have
  normal phenotype
• Phenylketonuria (PKU) single gene, autosomal
  recessive, can be diagnosed at birth, diet can
  treat, carriers have normal phenotype
• Huntingtons disease single gene, autosomal
  dominant, onset late in life (so patients likely
  to reproduce prior to diagnosis), no carriers
• Heart disease, high blood pressure multiple
  genes, no simple pattern of inheritance, genes
  increase susceptibility
• Lebers hereditary neuropathy mitochondrial,
  relatively late onset, inherited from mother only

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Five general categories of genetic disorders exist

• Single gene (Mendelian) disorders
• Polygenic (multifactorial) traits
• Mitochondrial diseases
• Chromosomal abnormalities (Lecture 10)
• Diseases of unknown etiology (causes) that run
  in families

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Examples of multifactorial ( polygenic
inheritance) diseases
Heart disease, hypertension, diabetes,
obesity, many cancers, cleft palate (and many
more)
On a pedigree, polygenic diseases do tend to run
in families, but the inheritance does not fit
simple patterns as with Mendelian diseases. But
this does not mean that the genes cannot
eventually be located and studied. There is also
a strong environmental component to many of them
(e.g., blood pressure).
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Genetic diseases to know for IB150

• Tay-Sachs disease single gene, autosomal
  recessive, early lethal, no homozygotes
  reproduce, carriers have normal phenotype
• Sickle cell anemia single gene, autosomal
  recessive, condition can be treated, carriers may
  have symptoms (sickle cell trait)
• Cystic fibrosis single gene, autosomal
  recessive, life can be prolonged, carriers have
  normal phenotype
• Phenylketonuria (PKU) single gene, autosomal
  recessive, can be diagnosed at birth, diet can
  treat, carriers have normal phenotype
• Huntingtons disease single gene, autosomal
  dominant, onset late in life (so patients likely
  to reproduce prior to diagnosis), no carriers
• Heart disease, high blood pressure multiple
  genes, no simple pattern of inheritance, genes
  increase susceptibility
• Lebers hereditary neuropathy mitochondrial,
  relatively late onset, inherited from mother only

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Five general categories of genetic disorders exist

• Single gene (Mendelian) disorders
• Polygenic (multifactorial) traits
• Mitochondrial diseases
• Chromosomal abnormalities (Lecture 10)
• Diseases of unknown etiology (causes) that run
  in families

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Mitochondrial DNA

• Humans 16,000 bases
• Not a linear chromosome
• Similar to bacterial DNA
• Genes for rRNA (2), tRNA (22), 13 proteins in the
  electron transport chain that produces ATP

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(No Transcript)
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Mitochondrial inheritance
Maternal inheritance
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Mitochondrial Patterns of Inheritance
Most mitochondrial genes are associated
with Metabolism - energy production - so
mitochondrial disorders often involve metabolism
(Lebers hereditary optic neuropathy - causes
loss of central vision - not enough cellular
energy provided to the cells in the retina)
In this case pedigree analysis is simple
All children of affected males WILL NOT inherit
the disease.  All children of affected females
WILL inherit it. There are NO carriers.
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Genetic diseases to know for IB150

• Tay-Sachs disease single gene, autosomal
  recessive, early lethal, no homozygotes
  reproduce, carriers have normal phenotype
• Sickle cell anemia single gene, autosomal
  recessive, condition can be treated, carriers may
  have symptoms (sickle cell trait)
• Cystic fibrosis single gene, autosomal
  recessive, life can be prolonged, carriers have
  normal phenotype
• Phenylketonuria (PKU) single gene, autosomal
  recessive, can be diagnosed at birth, diet can
  treat, carriers have normal phenotype
• Huntingtons disease single gene, autosomal
  dominant, onset late in life (so patients likely
  to reproduce prior to diagnosis), no carriers
• Heart disease, high blood pressure multiple
  genes, no simple pattern of inheritance, genes
  increase susceptibility
• Lebers hereditary neuropathy mitochondrial,
  relatively late onset, inherited from mother only

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Genetic diseases to know for IB150

• Tay-Sachs disease single gene, autosomal
  recessive, early lethal, no homozygotes
  reproduce, carriers have normal phenotype
• Sickle cell anemia single gene, autosomal
  recessive, condition can be treated, carriers may
  have symptoms (sickle cell trait)
• Cystic fibrosis single gene, autosomal
  recessive, life can be prolonged, carriers have
  normal phenotype
• Phenylketonuria (PKU) single gene, autosomal
  recessive, can be diagnosed at birth, diet can
  treat, carriers have normal phenotype
• Huntingtons disease single gene, autosomal
  dominant, onset late in life (so patients likely
  to reproduce prior to diagnosis), no carriers
• Heart disease, high blood pressure multiple
  genes, no simple pattern of inheritance, genes
  increase susceptibility
• Lebers hereditary neuropathy mitochondrial,
  relatively late onset, inherited from mother only

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Lecture 8 Mendelian Inheritance in Humans
Readings Ch. 14
Understand the use of pedigree analysis to
determine patterns of inheritance in humans.
inherited disorders genetic diseases.  Name the
5 categories of genetic diseases observed in
humans. single gene disorders multifactorial
(polygenic) traits chromosomal abnormalities
mitochondrial inheritance diseases of unknown
etiology Identify the conventional symbols used
to depict human family trees. pedigree Name the
5 categories of single gene (Mendelian)
disorders. autosomal recessive autosomal
dominant multifactorial, chromosomal, and
mitochondrial, unknown etiology
 Give examples of autosomal recessive traits and
be able to identify the pattern of inheritance.
cystic fibrosis Tay-Sachs sickle cell
disease Give examples of autosomal dominant
traits and be able to identify the pattern of
inheritance. Huntington Disease Give examples of
mitochondrial traits and be able to identify the
pattern of inheritance. Lebers hereditary
optic neuropathy