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Transmission Genetics:
Heritage from Mendel
Mendel’s Genetics
• Experimental tool: garden pea
• Outcome of genetic cross is independent
of whether the genetic trait comes from
the male or female parent
• Reciprocal genetic crosses
produce the same results
• Many human traits follow
this pattern of inheritance
Mendel’s Experiments
• Gene : inherited trait
• Plants with different
forms of a trait, such as
yellow vs. green seeds
(alleles) were genetically
crossed
• Mendel counted the number of offspring
with each trait (F1), (e.g.: green seeds)
• He crossed F1 plants among themselves
and counted F2 offspring
Mendel’s Observation
• Genetic cross between parents that
“breed true” for a pair of traits, round
seeds vs. wrinkled seeds, produces
offspring with round seeds only (F1)
• Round seeds are dominant
• Each parent has two identical copies of
the genetic information specifying the trait
(homozygous) and contributes one in
each cross (P1)
Mendel’s Hypothesis
• Round seed parent
“AA” = genotype
• Wrinkled seed parent
“aa” = genotype
• Round seed parent contributes “A”
gamete to offspring
• Wrinkled seed parent contributes “a”
gamete to offspring
Law of Dominance
• Offspring genotype = A + a = Aa
heterozygous
• All offspring produce round seeds
although they are genetic composites of
“Aa” because “A” (round) is dominant to
“a” (wrinkled)
Law of Segregation
• F1 genotype =“Aa”= monohybrid
• “Aa” parent produces either “A” or “a”
gametes in equal proportion
Law of Segregation
(simple consequence of two chromosomes)
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 = recessive
Monohybrid Genetic Cross
Chart Title: Monohybrid genetic Cross
Parents: Aa X Aa
gametes: A or a
each parent produces A and a gametes and contributes one gamete at fertilization
1/4
AA
round seeds
dominant
1/2
Aa
round seeds
dominant
1/4
aa
wrinkled seeds
recessive
Mendelian Ratios
• Genotypic ratios differ from phenotypic
ratios since dominant phenotype consists
of AA” and “Aa”
• F2 results of monohybrid cross show 3:1
round:wrinkled phenotypic ratio
• Genotypic ratios of monohybrid cross are
1:2:1 = 1/4 AA + 1/2 Aa + 1/4 aa
Testcross Analysis
• Testcross analysis allows geneticist to
determine whether observed dominant
phenotype is associated with a
homozygous “AA” or heterozygous “Aa”
genotype
• Genetic cross is performed using a
recessive testcross parent = “aa”
Testcross Results
• AA + aa = Aa ;
dominants only
parent homozygous
• Aa + aa = 1/2 Aa + 1/2 aa
produces 1/2 dominant, 1/2 recessive
parent heterozygous
Dihybrid Cross Ratios
• two different phenotypic
traits, such as seed color
(yellow vs. green) and
seed shape (round vs. wrinkled)
• Analysis of all combinations: (3:1 round :
wrinkled and 3:1 yellow : green) produces
9:3:3:1 phenotypic ratio (round/yellow :
round/green : wrinkled/yellow :
wrinkled/green
Dihybrid F2
Law of Independent Assortment
• Combinations of individual elements
within dihybrid pair generate genotypic
ratios for dihybrid cross
• True for any number of unlinked genes
• Also a consequence of distinct
chromosomes
Dihybrid Testcross
• WwGg gametes = WG
+ wG +Wg + wg = 1:1:1:1
ratio;
• double recessive gametes = wg
• Offspring = WwGg + wwGg + Wwgg +
wwgg = 1:1:1:1 ratio
• Testcross shows that parent is
heterozygous for both traits (dihybrid)
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: 27:9:9:9:3:3:3:1
Probability Rules
• Addition Rule: The probability of obtaining
one or the other of two mutually exclusive
events is the sum of their individual
probabilities
• Multiplication Rule: The probability of two
independent events occurring
simultaneously equals the product of their
individual probabilities
Mendelian Probabilities
• Dihybrid crosses also follow sum rule and
product rule to determine outcome
probabilities
• Phenotypic outcome = 9:3:3:1
• Genotypic outcome = 1:2:1:2:4:2:1:2:1
Pedigree Analysis
• In humans, pedigree analysis is used to
determine individual genotypes and to predict
the mode of transmission of single gene traits
• To construct a pedigree, the pattern of
transmission of a phenotypic trait among
individuals in a family is used to determine
whether the mode of inheritance is dominant
or recessive
• Pedigree analysis is used to study single
gene disorders, such as Huntington’s
Disease, a progressive neurodegenerative
disorder
Pedigree Analysis: Dominance
• Dominant phenotypic traits usually appear in
every generation of a pedigree
• About 1/2 the offspring of an affected
individual are affected
• The trait
appears in
both sexes if
the gene is
not on the X
chromosome
Dominant Single Gene
Disorders
Transmission Probabilities for Dominant Single Gene Traits
most common cross
Aa X aa
Aa = affected
aa = nonaffected
Aa
affected heterozygote
prob = 1/2
A = defective genetic element
aa
nonaffected recessive
prob = 1/2
a = nonaffected genetic element
Pedigree Analysis: Recessive
• Pedigree analysis can used to distinguish
dominant vs. recessive modes of inheritance
for traits determined by single genes
• Analysis of patterns of transmission of
recessive genes is used to identify carriers of
recessive traits which cannot be determined
by direct phenotypic analysis
• Recessive traits occur in individuals whose
parents are phenotypically dominant
Inheritance of Recessive Genes
• Two phenotypically dominant people who
produce a child with a recessive genetic
disorder:
1/4 probability
that any of their
children will be
affected and 1/2
that they will be
carriers
Recessive Genetic Disorders
Inheritance of Recessive Single Gene Disorders
most common cross
Aa X Aa
A = nonaffected gene
a = affected gene
AA
prob = 1/4
nonaffected
Aa
prob =1/2
carrier
aa
prob = 1/4
affected
Incomplete Dominance
• Heterozygote phenotype is
intermediate between
dominant and recessive
phenotypes (snapdragons)
• F1 of cross between dominant
(red) and recessive (ivory)
plants shows intermediate
phenotype (pink)
• F2 products show identical phenotypic and
genotypic ratios
Multiple Alleles/Co-dominance
• For some traits more than two alleles exist in
the human population
• ABO blood groups are specified by three
alleles which specify four blood types
• ABO blood group inheritance also illustrates
principle of co-dominance in which both
alleles contribute to the phenotype in the
heterozygote
• Antibodies are proteins which bind to
stimulating molecules = antigens
Multiple Alleles/Co-dominance
• IA and IB are dominant to IO, genotype AIO =
type A; IBIO = type B
• IA and IB are
co-dominant; each
allele specifies
antigen: genotype
IAIB = type AB
• IO = is recessive
genotype IOIO
Biochemical Genetics
• Many recessive genes code for enzymes
which carry out specific steps in
biochemical pathways
• Mutations which alter the structure of
genes block enzyme production if both
copies of the gene are defective
• Disorders were termed “inborn errors of
metabolism” by Garrod
Biochemical Genetics
• Recessive genes often
contain mutations
which block the
formation of gene
product (ww)
• Heterozygotes which contain one
recessive gene copy (Ww) may produce
only 1/2 the amount of protein specified by
the homozygous dominant (WW) which
contains two functional copies of the gene
Biochemical Genetics
• Heterozygotes (Ww) may still produce
sufficient gene product to display
dominant phenotype = round seed;
genotype = carrier
• For some genes reduction of gene product
by 1/2 in the heterozygote may be
physiologically significant, especially for
structural proteins = dominant disorders
Biochemical Genetics
• Variable expressivity refers to genes that
are expressed to different degrees in
different individuals, e.g.: severity of an
inherited disease
• Incomplete penetrance means that the
phenotype predicted from a specific
genotype is not always expressed, e.g.:
individual inherits mutant gene but shows
no effect
Genetic Epistasis
• Epistasis alters Mendelian
9:3:3:1 phenotypic ratios
in dihybrid inheritance
• In epistasis, two sets of
genetic elements interact
to produce a single
phenotype, which modifies
the observed phenotypic
ratios
• Mendelian pattern of inheritance
Genetic Complementation
• Complementation tests are used to
determine if different phenotypes result
from variations in one gene
• Homozygous recessive genotypes which
are genetically crossed can only produce
a dominant
phenotype if the
recessive genetic
elements are
located on
different genes
Genetic Complementation
• A mutant screen is an experiment which
generates mutations which affect specific
phenotypes
• Multiple alleles refer to the various forms
of a gene
• Wildtype refers to the phenotype for a
specific trait most commonly observed
Genetic Complementation
• The complementation test groups mutants
into allelic classes called
complementation groups
• Lack of complementation = two mutants
are alleles of the same gene
• Principle of Complementation: two
recessive allelic mutations produce
mutant phenotype; two non-allelic
recessive mutations show no effect