Download Chapter 4 Extensions of Mendelism

José A. Cardé, PhD
Universidad Adventista
de las Antillas
Agosto 2011
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Allelic Variation and Gene Function
Gene Action: From Genotype to Phenotype
Inbreeding: Another Look at Pedigrees
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Mendel’s traits showed two distinct forms
Most genes do not exhibit simple inheritance
Genotypic ratios persist but phenotypic
ratios may vary due to “outside-the-gene”
influences including
- Multiple alleles
- Gene linkage
- Epistasis
- Codominance,
- Incomplete penetrance
- Environment
The diverse kinds of alleles of genes affect phenotypes in different ways.
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Each trait that Mendel studied was controlled
by a single gene with two alleles.
Genes may have more than 2 alleles.
Different alleles may affect the phenotype in
different ways.
The heterozygous phenotype is between
those of the two homozygotes
Example: Familial hypercholesterolemia
(FH)
- A heterozygote has approximately half the
normal number of receptors in the liver for LDL
cholesterol
- A homozygous for the mutant allele totally lacks
the receptor, and so their serum cholesterol level
is very high
The phenotype of the
heterozygote is
midway between the
phenotypes of the
two homozygotes.
 One allele is partially,
or incompletely,
dominant over the
other.
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The heterozygous phenotype results from
the expression of both alleles
The ABO gene encodes a cell surface
protein
- IA allele produces A antigen
- IB allele produces B antigen
- i (IO) allele does not produce antigens
Alleles IA and IB are codominant between
them, and both are completely dominant
to i
Figure 5.3
The heterozygote
expresses the
phenotypes of both
homozygotes.
 Neither allele is
dominant.
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Offspring from Parents with
Blood Type A and Blood Type B
Figure 5.4
Figure 5.4
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An individual carries two alleles for each
autosomal gene
However, a gene can have multiple alleles
because its sequence can deviate in many
ways
Different allele combinations can produce
variations in the phenotype
- PKU gene has hundreds of alleles
resulting in four basic phenotypes
- CF gene has over 1500 alleles
The most common
alleles in nature is the
wild-type allele.(+/+)
 All other alleles are
mutants.(ch,h,0)
 The gene is represented
with the letter of the
mutant (c)
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Alelos Múltiples : Tipos de Sangre ABO
Relación funcional entre miembros de grupo de alélos múltiples
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An allelic series describes
the dominance hierarchy
of multiple alleles.
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A null allele is
nonfunctional.
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A hypomorphic allele has
partial function.
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Visible mutations - color o textura, muchas
recesivas, pocas dominantes
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Sterile mutations- limitan las reproducción,
dom o reces, afectan ambos sexos o a
uno de los dos
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Lethal mutations - interfieren con
funciones vitales, muerte
A lethal genotype causes death before the
individual can reproduce
- This removes an expected progeny class
following a specific cross
A double dose of a dominant allele may be
lethal
- Examples:
- Achondroplastic dwarfism
- Mexican hairless dogs
- Brachydactyly, recesive homocigote
Lethal Alleles
Figure 5.1
Figure 5.1b
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Genes often have multiple alleles.
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Mutant alleles may be dominant, recessive, incompletely
dominant, or codominant.
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If a hybrid that inherited a recessive mutation from each of
its parents has a mutant phenotype, then the recessive
mutations are alleles of the same gene; if the hybrid has a
wild phenotype, then the recessive mutations are alleles of
different genes.
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Most genes encode polypeptides.
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In homozygous condition, recessive mutations often abolish
or diminish polypeptide activity.
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Some dominant mutations produce a polypeptide that
interferes with the activity of the polypeptide produced by
the wild-type allele of a gene.
Phenotypes depend on both environmental and genetic factors.
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Genes function in a biological and physical
environment.
Examples
 Drosophila shibire mutation (temperature)
 Phenylketonuria (diet)
 Pattern baldness (gender)
Penetrance refers to the all-or-none
expression of a single gene
Expressivity refers to the severity or extent
A genotype is incompletely penetrant if some
individuals do not express the phenotype
A phenotype is variably expressive if
symptoms vary in intensity among different
people
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Individuals do not
express a trait even
though they have the
appropriate
genotype.
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A trait is not
manifested uniformly
among individuals
that show it.
Penetrance refers to the all-or-none
expression of a single gene
Expressivity refers to the severity or extent
A genotype is incompletely penetrant if some
individuals do not express the phenotype
A phenotype is variably expressive if
symptoms vary in intensity among different
people
The phenomenon where one gene affects the
expression of a second gene
Example: Bombay phenotype
- The H gene is epistatic to the I gene
- H protein places a molecule at the cell surface to
which the A or B antigens are attached
- hh genotype = no H protein
- Without H protein the A or B antigens can not be
attached to the surface of the RBC
- All hh genotypes have the phenotype of type O,
although the ABO blood group can be
anything (A, B, AB, or O)
Epistasis
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In epistasis, an allele of one gene overrides the
effect of other genes on the phenotype.
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In Drosophila,
 The cinnabar mutation produces bright red eyes.
 The white mutation produces white eyes.
 When both mutations are present in the same fly, the eyes
are white.
 The white mutation is epistatic to the cinnabar mutation.
Different combinations
of alleles from two genes
result in different
phenotypes.
 In this example,
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R-P- produces walnut
R-pp produces rose
rrP- produces pea
rrpp produces single
Rose RRpp y Pea son rrPP
- F1 = RrPp = Walnut
F2 – 9/16 R_P_: 3R_pp, :
3rrP_:1 rrpp
Demuestra que dos genes q
se sortean independientes
pueden afectar un mismo
rasgo
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A gene that affects many
phenotypes is pleiotropic.
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Mutations in the
phenylketonuria gene cause
mental impairment, light hair
color, and the presence of
metabolites in blood and
urine.
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Mutations in the Drosophila
singed gene affect bristle
shape and egg production.
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The phenomenon where one gene controls
several functions or has more than one
effect
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Example: Porphyria variegata
- Affected several members of European
Royal families, including King George III
- The varied illnesses & quirks appeared to
be different unrelated disorders
Pleiotropy
Figure 5.5
Figure 5.5a
Figure 5.5b
Photo © North Wind Picture Archives
Figure 5.6
Figure 5.7
Gene action is affected by biological and physical
factors in the environment.
 Two or more genes may influence a trait.
 A mutant allele is epistatic to a mutant allele of
another gene if it has an overriding effect on the
phenotype.
 A gene is pleiotropic if it influences many different
phenotypes.
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Geneticists use a simple statistic, the inbreeding coefficient, to analyze the
effects of matings between relatives.
Inbred lines of
experimental species are
often less vigorous than
hybrid lines.
 Inbred lines of selffertilized plants are
homozygous for alleles
that were present in the
founding line.
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When two different
inbred lines are
crossed, the hybrids
are heterozygous for
many genes.
 These heterozygotes
display heterosis, or
hybrid vigor.
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Individuals A and B are
half-siblings.
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Their offspring, I, is inbred,
and inherited one copy of
her genes from A and one
copy from B.
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These copies may be
identical by descent if
they are identical copies
inherited from individual C.
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C is the common ancestor
of I.
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The Inbreeding Coefficient, F, is the probability
that the two gene copies in an individual are
identical by descent from a common ancestor.
Calculation of the Inbreeding Coefficient
1)
2)
3)
Identify the common ancestor(s) of an inbred individual.
Count the number of individuals (n) in each inbreeding
loop.
Calculate the quantity (1/2)n for each inbreeding loop
and sum the results.
1)
Insert Unmarked
Figure
Figure number
Chapter 4 p. 725 top
left
2)
3)
Identify the common
ancestor(s).
 C is the common
ancestor, so there is one
inbreeding loop.
Count the number of
individuals in each
inbreeding loop.
 The Loop includes C, A,
and B; n=3
Calculate (1/2)n for each loop
and sum the results.
 There is only one loop in
this case
 (1/2)3 = 1/8, so F = 1/8
1)
Identify the common
ancestor(s).
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2)
Count the number of
individuals in each
inbreeding loop.
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3)
U and V are both common
ancestors, so there are two
inbreeding loops.
Loop 1: U, R, S; n=3
Loop 2: V. R, S; n=3
Calculate (1/2)n for each
loop and sum the results.
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Loop 1: (1/2)3 = 1/8
Loop 2: (1/2)3 = 1/8
F = 1/8 + 1/8 = 1/4
De donde sale el 1/8?:
Insert Unmarked
Figure
Figure Number p.
726 top left (intext art)
De donde sale el 1/8: 1/8 es la p de que cualquiera de los
alelos sea heredado al individuo I; ¼ por A y ¼ por B; y
1/16 para uno de los alelos y 1/16 para el otro.
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Multiply (1/2)n by the
term [1 + FCA]
FT = (1/2)3  [1 + (1/2)3]
= 1/8  (1 + 1/8)
= 9/64
RESUMEN
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Calculate the fraction of genes that two relatives
share
Calculate the inbreeding coefficient for the
offspring of a mating between the two relatives
The coefficient of relationship = F  2
For full siblings, F = 1/4, so the coefficient of
relationship is 1/2
This means that full siblings share 1/2 of their genes
Inbreeding increases the frequency of homozygotes
and decreases the frequency of heterozygotes.
 The effects of inbreeding are proportional to the
inbreeding coefficient, which is the probability that
two gene copies in an individual are identical by
descent from a common ancestor.
 The coefficient of relationship is the fraction of
genes that two individuals share by virtue of
common ancestry.
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