Transcript Freeman 1e: How we got there - Londonderry School District

EXTENSIONS OF MENDELIAN GENETICS
• What happens when inheritance
doesn’t follow the patterns observed
by Mendel?
• There are many reasons why traits
might deviate from expected.
Main Concepts
•Alleles Alter Phenotypes in Different Ways
•Incomplete Dominance
•Codominance
•Multiple Alleles
•Lethal Alleles
•Phenotypes Often Affected by More Than
One Gene (Polygenic)
•A Single Gene May Have Multiple Effects
(Pleiotropy)
•Sex Linked Traits
•Sex-Limited and Sex-Influenced Inheritance
• How are alleles formed?
• MUTATION
• Wild-type allele: occurs most
frequently in nature and is usually
dominant
• Different types of mutations can alter
alleles (or produce new ones)
Mutations
• Loss of function mutation: a mutation
that causes the reduction/loss of the
specific wild-type function
• If the loss is complete, the mutation
has resulted in what is called a null
allele
• Gain of function mutation: a
mutation that enhances the function
of the wild-type allele
Incomplete Dominance
• Incomplete dominance –
heterozygotes show a distinct
intermediate phenotype different
from homozygous genotypes
• Neither trait is dominant
Symbols
• Alleles that are incompletely
dominant are written using a
superscript letter.
• Flower color:
• CWCW (white) plant X CRCR (red) plant
will produce all CRCW offspring
• Are these traits blended?
• NO … the alleles are particulate (they
remain separate and do not influence
each other).
• How do we know?
• A cross of two pink individuals will
produce red, white and pink
individuals.
• The phenotypic ratio will be 1:2:1, like
the genotypic ratio
Figure 4-1
Copyright © 2006 Pearson Prentice Hall, Inc.
Incomplete Dominance
• What is really going on?
• White allele is most likely a “loss of
function” mutation
• Wild type (red) “codes” for synthesis of
red pigment
• Mutant allele (white) cannot synthesize
the pigment
• Therefore, the heterozygote only
produces ½ the amount of pigment
(pink)
• True incomplete dominance is rare
• Individuals may appear completely
dominant until viewed at the
molecular level
• Tay-Sachs disease
• Homozygous recessive = severely
affected, death before age 3
• Heterozygotes appear normal, but only
produce about 50% of normal enzymes
• Threshold effect
• The threshold effect - normal
phenotypic expression occurs
whenever a certain level (≤ 50%) of
gene product is attained.
Codominance
• Codominance – 2 alleles affect the
phenotype in separate,
distinguishable ways
• Alleles for curly hair and straight hair
are codominant
• Curly hair = homozygous for curly
hair alleles
• Straight hair = homozygous for
straight hair alleles
• Heterozygous individuals have wavy
hair
Incomplete Dominance vs.
Codominance
• With incomplete dominance we get a
reduced function of the dominant trait
(due to recessive), so that the third
phenotype is something in the middle
(red x white = pink).
• In codominance, the "recessive" &
"dominant" traits appear together in
the phenotype of hybrid organisms –
appears to be a “blend”
Dominance = common?
• Polydactyly –
an allele that is
dominant to the
recessive allele
for 5 digits
• Recessive
allele more
common – 99%
have 5 digits
Multiple Alleles
• Can only be studied in populations
• WHY?
• Because individuals can only have 2
alleles for a gene!
• Example of trait covered by multiple
alleles?
• Human Blood Type
• ABO antigens
• ABO blood groups in humans are
determined by three alleles, IA, IB,
and IO (also referred to as i)
• Both the IA and IB alleles are dominant
to the IO allele
• The IA and IB alleles are codominant to
each other
• I stands for “isoagglutinogen”, which
is another word for antigen.
How many blood types are possible?
• Because each individual carries two
alleles, there are six possible
genotypes and four possible blood
types
• IA IA or IAIO- type A
• IB IB or IBIO- type B
• IA IB - type AB
• IOIO - type O
Table 4-1
Copyright © 2006 Pearson Prentice Hall, Inc.
• The blood types differ due to the
molecules that are present on the
outside of RBC (antigens)
Lethal Alleles
• Loss of function mutation
• Can (sometimes) be tolerated in
heterozygous state
• Can have a mutant phenotype (acts
dominant) when heterozygous
• BUT… may be lethal in the homozygous
state
y
Figure 4-4
Copyright © 2006 Pearson Prentice Hall, Inc.
Lethal alleles
• In some cases, the lethal allele is
DOMINANT, so even heterozygotes
will die.
• Why does this allele persist in the
population?
• Late acting (Huntington’s)
• Individuals reproduce before allele
takes affect
Polygenic Traits
• Many traits with a distinct
phenotype are affected by more
than one gene
• The cellular function of numerous
gene products contributes to the
development of a common
phenotype
• Ex - skin color in humans is
controlled by at least 3 different
genes
• Imagine - each gene has 2
alleles, (light/dark), demonstrate
incomplete dominance
• AABBCC (dark) and aabbcc
(light)
• Cross between 2 AaBbCc
(intermediate) produces wide range
of shades
Epistasis
• Epistasis - a gene at one locus alters
the phenotypic expression of a gene
at a second locus
• One gene can mask the effect of
the other gene
• Two gene pairs can complement
each other, such that one dominant
allele is required at each locus to
express a certain phenotype
Epistasis example
• Mice (and many other mammals) - coat
color depends on two genes
• One (epistatic gene), determines whether
pigment will be deposited in hair
• Presence (C) is dominant to absence (c)
• Second determines whether pigment
deposited is black (B) or brown (b)
• The black allele is dominant to the brown
allele
• Individual with cc has a white (albino)
coat regardless of the genotype of the
2nd gene
Epistasis – more complex
• In cats (and other mammals), a
pattern of hair termed “agouti” is an
example of epistasis
• Some cats have hairs in which there
is more than one color distributed
along the hair shaft (banded –
agouti)
• Agouti fur color is typical of many
wild animals such as mice squirrels
and rabbits – good for camouflage!
• Agouti is determined by the
dominant agouti allele, A
• Hairs on non-agouti cats are
unbanded, producing a solidly
colored coat
• Such a cat is homozygous for the
non-agouti allele (aa) at the agouti
locus
• Again – regardless of color. SO …
you could have an agouti brown,
agouti black, etc.
Epistasis Ratios
• When studying a single
characteristic, a ratio expressed in
16 parts (e.g., 3:6:3:4) suggests that
epistasis is occurring.
Pleiotropy
• Pleiotropy occurs when expression
of a single gene has multiple
phenotypic effects, and it is quite
common
• For example, the wide-ranging
symptoms of sickle-cell disease are
due to a single gene
• Marfan syndrome
• What US president may
have had Marfan?
The Environment
• Phenotype is not always a direct
expression of genotype
• The environment plays a role in a
gene’s expression.
Environmental Mutations
• Conditional or temperature-sensitive
mutations - mutations affected by
temperature
• useful in studying mutations that affect
essential processes
• Nutritional mutations – mutations
affected by diet
• may prevent phenotype from reflecting
genotype. Ex -mutations in a biosynthetic
pathway
X-linked or Sex linked traits
• Genes are located on the X
chromosome
• Present a unique pattern of
inheritance due to the presence of
only one X chromosome in males
• Females (XX) can be heterozygous
(carriers), while their sons (XY) can
express the disease/trait.
• Drosophila (fruit fly) eye color was
one of the first examples of Xlinkage described
• Drosophila was a favorite model
organism for Thomas Hunt Morgan
• Morgan studied eye color in fruit flies
– the trait did not have normal
Mendelian ratios
• Crosses of white-eyed male with a
red-eyed female - all F1 offspring
had red eyes
• The red allele appeared dominant
• Crosses between F1 produced
classic 3:1 ratio
• Surprisingly, the white-eyed trait
appeared only in males
• All the females and half the males had
red eyes
• Morgan concluded that a fly’s eye
color was linked to its sex
Figure 4-11
Copyright © 2006 Pearson Prentice Hall, Inc.
Figure 4-12
Copyright © 2006 Pearson Prentice Hall, Inc.
p
Table 4-3
Copyright © 2006 Pearson Prentice Hall, Inc.
• Lethal X-linked recessive disorders
are observed only in males, since
females can only be heterozygous
carriers that do not develop the
disorders.