Transcript Training - Tistory

2
Transmission Genetics
Heritage from Mendel
Gregor Mendel
• G. Mendel carried out his experiments from 1856 to
1863 in a small garden plot nestled in a corner of the
St. Thomas monastery in the town of Brno
• He published the results and his interpretation in its
scientific journal in 1866
• Mendel’s paper contains the first clear exposition of
the statistical rules governing the transmission of
hereditary elements from generation to generation
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Mendel’s Genetic Hypothesis
• Each parent contributes to its progeny distinct
elements of heredity = factors = genes
• Factors remain unchanged as they pass through
generations
• Mendel thought in quantitative, numerical terms,
looked for statistical regularities in the outcome
from his crosses
3
Mendel’s Experiments
• Experimental organism: garden pea, Pisum
sativum
• Advantages: many known varieties with different
alternative traits, self-fertilization, easy artificial
fertilization
• True-breading varieties = self-fertilized plants
produce only progeny like themselves
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Fig. 2.1
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Mendel’s Experiments
• True-breading plants with different forms of a trait,
such as yellow vs. green seeds
• All of the F1 progeny exhibited only one parental
trait (green seeds)
• In F2 generation obtained by self-fertilization of F1
plants, the observed ratio of visible traits was
3 green : 1 yellow
• Outcome of cross was independent of whether the
trait came from the male or female parent:
reciprocal crosses produced the same result
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Fig. 2.3
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Mendel’s Hypothesis
• Each parent has two identical copies of the genetic
information specifying the trait = homozygous
• Each gamete contains only one copy of a hereditary
factor specifying each trait
• Random fertilization unites two copies of the gene
in the progeny
• F1 progeny contains different variants (alleles) of
the gene = heterozygous
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Mendel’s Hypothesis
• The genetic constitution of an organism =
genotype
• The observable properties of an organism =
phenotype
• In the cross between round and wrinkled seed pea
plants:
• Round seed parent has two identical copies of
genetic information = its genotype = AA
• The genotype of a wrinkled seed parent = aa
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Dominance
• Round seed parent contributes “A” gamete to
offspring
• Wrinkled seed parent contributes “a” gamete to
offspring
• Offspring genotype = A + a = Aa contains one copy of
“A” and one copy of “a”
• All offspring produce round seeds although their
genotype is “Aa” because “A” is dominant and
“a” is recessive
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Fig. 2.6
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Segregation
• When an F1 plant is self-fertilized, the A and a
determinants segregate from one another and are
included in the gametes in equal numbers
• The gametes produced by segregation come
together in pairs at random to yield the progeny of
the next generation
• In the F2 generation, the ratio of the progeny with
dominant trait to the progeny with recessive trait is
3:1. In case of round and wrinkle seeds, 3/4 round
and 1/4 wrinkled offspring
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The Principle of Segregation
• The Principle of Segregation: In the formation of
gametes, the paired hereditary determinants
(genes) segregate in such a way that each gamete
is equally likely to contain either member of the
pair
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Monohybrid Genetic Cross
• Genetic cross : Aa X Aa produces A and a
gametes from each parent
• Punnett square shows four possible outcomes =
AA, Aa, aA, and aa
• Three combinations = AA, Aa, and aA produce
plants with round seeds and display a round
phenotype
• Fourth combination = aa displays wrinkled
phenotype
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Monohybrid Genetic Cross
Parents: Aa X Aa
each parent produces A and a gametes and
contributes one gamete at fertilization
1/4
AA
round
dominant
1/2
Aa
round
dominant
1/4
aa
wrinkled
recessive
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Round vs. Wrinkled: Modern Context
• The gene that determines the shape of a seed
encodes an enzyme, starch-branching enzyme I
(SBEI), required to synthesize a branched-chain
form of starch known as amylopectin
• Round (W) seeds contain amylopectin and shrink
uniformly as they dry
• Wrinkled (w) seeds lack amylopectin and shrink
irregularly
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Round vs. Wrinkled: Modern Context
• Wrinkled peas have an inborn error in starch
metabolism
• The molecular basis of the wrinkled (w) mutation =
SBEI gene is interrupted by the insertion of a DNA
sequence called a transposable element
• Transposable elements = DNA sequences capable
of moving (transposition) from one location to
another
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Round vs. Wrinkled: Modern Context
• A procedure called gel electrophoresis is used
to separate DNA molecules of different sizes
• DNA fragment corresponding to the W form of
the SBEI gene moves farther than the w
fragment, because the w fragment is larger
(owing to the insertion of the transposable
element)
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Fig. 2.4A
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Fig. 2.4B
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Round vs. Wrinkled: Modern Context
• Classical geneticists studied primarily morphological
traits = the shape of a seed is manifestly round or
wrinkled
• Modern geneticists study morphological traits too, but
they supplement this with molecular traits = the
pattern of bands in a gel
• Morphological traits are frequently dominant or
recessive, but this is not necessarily true of molecular
traits
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Round vs. Wrinkled: Modern Context
• When alternative forms of a gene (W and w) can both
be detected when they are present in the cell, we say
that the forms of the gene are codominant
• Molecular traits are often (but by no means always)
codominant
• Dominance is not an intrinsic feature of a gene; it
rather depends on the method we chose to examine it
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Testcross Analysis
• Testcross = a cross, between an organism of
dominant phenotype (genotype unknown) and an
organism of recessive phenotype (genotype known
to be homozygous recessive)
• In a testcross, the relative proportion of the different
gametes produced by the heterozygous parent can
be observed directly in the proportion of
phenotypes of the progeny, because the recessive
parent contributes only recessive alleles
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Testcross Results
• AA + aa = Aa – testcross produces dominant
progeny only: parent homozygous
• Aa + aa = 1/2 Aa + 1/2 aa - testcross produces 1/2
dominant and 1/2 recessive individuals: parent
heterozygous
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Fig. 2.9
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Dihybrid Cross
• Mendel studied inheritance of two different traits,
such as seed color (yellow vs. green) and seed
shape (round vs. wrinkled) in the same cross =
dihybrid cross
• The F1 progeny were hybrid for both characteristics,
and the phenotype of the seeds was round
(dominant to wrinkled) and yellow (dominant to
green)
• In the F2 progeny, he observed the 9 round yellow : 3
wrinkled yellow : 3 round green : 1 wrinkled green
ratio
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Dihybrid Cross
• Mendel carried out similar experiments with
other combinations of traits. For each pair of
traits, he consistently observed the 9 : 3 : 3 : 1
ratio
• He also deduced the biological reason for the
observation:
• In the F2 progeny, if the 3 : 1 ratio of round:
wrinkled, is combined at random with the 3: 1
ratio of yellow: green, it yields the 9: 3: 3: 1
ratio of a dihybrid cross
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Fig. 2.10
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Independent Segregation
• The Principle of
Independent
Assortment:
Segregation of the
members of any
pair of alleles is
independent of the
segregation of
other pairs in the
formation of
reproductive cells.
Fig. 2.11
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Dihybrid Testcross
• The progeny of testcrosses show the result of independent
assortment
• The double heterozygotes produce four types of gametes in
equal proportions, the ww gg plants produce one type
• The progeny phenotypes are expected to consist of round
yellow, round green, wrinkled yellow, and wrinkled green in a
ratio of 1:1:1:1
This observation confirmed Mendel’s assumption that the
gametes of a double heterozygote included all possible
genotypes in approximately equal proportions
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Fig. 2.14
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Trihybrid Genetic Cross
• Trihybrid cross = three pairs of elements that
assort independently, such as WwGgPp
• For any pair phenotypic ratio = 3:1
• For two pairs ratio = 9:3:3:1
• Trihybrid cross pattern of segregation and
independent assortment is identical to dihybrid
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Probabilities
• Mendelian patterns of inheritance follow laws of
probability
• Addition Rule: The probability of the realization
of one or the other of two mutually exclusive
events, A or B, is the sum of their separate
probabilities
• Prob {WW or Ww} = Prob {WW} + Prob{Ww} =
0.25 + 0.50 = 0.75
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Fig. 2.15
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Probabilities
• Multiplication Rule:
The probability of two
independent events, A
and B, being realized
simultaneously is
given by the product
of their separate
probabilities
•
Prob {WG} = Prob {W}
x Prob{G} = 0.5 x 0.5 =
0.25
Fig. 2.16
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Pedigree Analysis
• In humans, pedigree analysis is used to determine
individual genotypes and to predict the mode of
transmission of single gene traits
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Autosomal Dominant
• Huntington disease is a progressive nerve
degeneration, usually beginning about middle age,
that results in severe physical and mental disability
and ultimately in death
• The trait affects both sexes
• Every affected person has an affected parent
• ~1/2 the offspring of an affected individual are affected
Fig. 2.18
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Autosomal Recessive
• Albinism = absence of pigment in the skin, hair,
and iris of the eyes
• The trait affects both sexes
• Most affected persons have parents who are not
themselves affected; the parents are heterozygous
for the recessive allele and are called carriers
• Approximately 1/4 of the children of carriers are
affected
• The parents of affected individuals are often
relatives
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Fig. 2.19
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Incomplete
Dominance
• Incomplete dominance = the
phenotype of the
heterozygous genotype is
intermediate between the
phenotypes of the
homozygous genotypes
• Incomplete dominance is
often observed when the
phenotype is quantitative
rather than discrete
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Multiple Alleles/Codominance
• Codominance means that the heterozygous genotype
exhibits the traits associated with both homozygous
genotypes
• Codominance is more frequent for molecular traits
than for morphological traits
• Multiple alleles = presence in a population of more
than two alleles of a gene
• ABO blood groups are specified by three alleles IA, IB
and IO
• IA and IB codominant, both IA and IB are dominant to IO
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Multiple Alleles/Codominance
People of
• blood type O make both anti-A and anti-B antibodies
• blood type A make anti-B antibodies
• blood type B make anti-A antibodies
• blood type AB make neither type of antibody
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Fig. 2.22
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Expressivity and Penetrance
• Variation in the phenotypic expression of a
particular genotype may happen because other
genes modify the phenotype or because the
biological processes that produce the phenotype
are sensitive to environment
• Variable expressivity refers to genes that are
expressed to different degrees in different
organism
• Penetrance refers to the proportion of organisms
whose phenotype matches their genotype for a
given trait. A genotype that is always expressed has
a penetrance of 100 percent
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Epistasis
• Epistasis refers to any type of gene
interaction that results in the F2
dihybrid ratio of 9 : 3 : 3 : 1 being
modified into some other ratio
• In a more general sense, it means
that one gene is masking the
expression of the other
• Flower color in peas: formation of
the purple pigment requires the
dominant allele of both the C and P
genes: the F2 ratio is modified to 9
purple: 7 white
Fig. 2.24
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Epistasis
• There are nine possible dihybrid ratios when both
genes show complete dominance
• Examples:
• 9:7 occurs when a homozygous recessive mutation in
either or both of two different genes produces the
same phenotype
• 12:3:1 results when a dominant allele of one gene
masks the genotype of a different gene
• 9:3:4 is observed when homozygosity for a recessive
allele masks the expression of a different gene
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Fig. 2.25
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The Principal of Complementation
• The Principle of Complementation: If two
recessive mutations are alleles of the same
gene, then the phenotype of an organism that
contains one copy of each mutation is mutant;
if they are alleles of different genes, then the
phenotype of an organism that contains one
copy of each mutation is wildtype (nonmutant)
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Complementation
• Complementation means that the mutations are in
different genes
• Mutations in the same gene do not complement
each other
• Complementation group - a group of mutations that
fail to complement each other
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Fig. 2.27
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Complementation
• The complementation test enables one to group
mutations into allelic classes
• A mutant screen is a large-scale, systematic
experiment designed to isolate multiple new
mutations affecting a particular trait
• A gene is defined experimentally as a set of mutant
alleles that make up one complementation group.
Any pair of mutant alleles in such a group fail to
complement one another and result in an organism
with a mutant phenotype
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