Download Ch 4 Extensions of Mendelian Genetics

1/21/2016
Ch 4 Extensions of
Mendelian Genetics
Exceptions to Mendelian Ratios
1
Alleles can alter phenotypes
•
Wild-type allele: allele most frequently seen in the
population
•
Loss-of-function allele: mutation alters gene in such a way
that the protein is less-functional or non-functional;
•
The degree to which the function is lost can vary. If the function is entirely
lost, the mutation is called a null mutation. Loss of function mutations are
typically recessive. When a heterozygote consists of the wild-type allele and
the loss-of-function allele, the level of expression of the wild type allele is
often sufficient to produce the wild type phenotype.
•
Null allele: above, but complete loss of function
2
1
1/21/2016
Alleles can alter phenotypes
•
And…
• Gain-of-function allele: mutation alters gene in
such a way that the protein’s function is enhanced
• Neutral mutations: mutation that does not alter
protein function
•
Remember the “Central Dogma of Molecular Biology”
is that DNA→mRNA→ribosome/tRNA→polypeptide
3
Nomenclature and symbols
• In Drosophila we can use this system for
distinguishing traits. In this example, ebony is the
recessive body color.
• e+ / e+ OR + / + - gray homozygote (WildType)
• e+ / e OR + / e - gray heterozygote (WildType)
• e / e OR e / e - ebony homozygote (mutant)
• We will also use other systems for distinguishing
traits.
4
2
1/21/2016
Incomplete Dominance
Crosses between true-breeding strains can produce
hybrids with phenotypes different from both parents.
Incomplete dominance
F1 hybrids that differ from both parents express
an intermediate phenotype.
Neither allele is dominant or recessive to the
other.
Phenotypic ratios are same as genotypic ratios
Codominance
F1 hybrids express phenotype of both parents
equally.
Phenotypic ratios are same as genotypic ratios.5
Snapdragons- Incomplete Dominance
Figure 4-1
1:2:1
Copyright © 2010 Pearson Education, Inc.
3
1/21/2016
Dominance Relationships
7
Co-dominance
Domesticated
10,000 years
1:2:1 in F2
8
4
1/21/2016
The terminus of H Antigen defines blood type
Co-dominance
9
Codominance
10
5
1/21/2016
A Gene May Have More Than 2 Alleles
11
Bombay Phenotype
12
6
1/21/2016
Individuals with genotype hh
do not make the H glycoprotein
(the molecular base for A and B)
Consequently it appears (types) as just oo)
13
The Bombay Phenotype
Copyright © 2010 Pearson Education, Inc.
7
1/21/2016
Example: many alleles of “white” eyes
Copyright © 2010 Pearson Education, Inc.
Recognized alleles for Brown Hair
16
8
1/21/2016
Agouti (A, dominant) gene has varied effects in mammal coat color
Named for cental/south american mammal;
They are related to guinea pigs
17
Mutations are the source of new alleles
Dominant A, and any other allele
“Dominance Series: A>at>a”
18
9
1/21/2016
The Agouti Yellow allele (AY) is dominant to A
but lethal when Homozygous (lethality is recessive)
i.e. AY AY do not exist
19
Figure 4-3
Copyright © 2010 Pearson Education, Inc.
10
1/21/2016
AY A
AY
AY
die
A
AY A
A
AY A
AY A
AA
2:1 phenotype ratio
21
Heterogeneous traits have multiple genes
underlying their expression
• Gene interaction
• It is not always possible to determine which of
many genes are mutated in a person with a
heterogeneous mutant phenotype.
Example – deafness in humans may be
caused by a mutant allele at one of more than
50 different genes.
22
11
1/21/2016
Epistasis – One gene’s alleles mask the
effects of another gene’s alleles
Epistasis: A gene interaction where the allele of
one gene masks/hides the effects of alleles of
another gene.
-The gene doing the masking is epistatic to the
gene being masked (hypostatic gene)
-Bombay phenotype is an example of epistasis
(hh is epistatic to which codes for A and B
antigens)
23
Figure 4-5
Not even close to 9:3:3:1 of a dihybrid cross
Copyright © 2010 Pearson Education, Inc.
12
1/21/2016
Labrador retriever example –
recessive epistasis
Coat color can be black, chocolate brown, or golden
yellow
B allele is dominant and determines black.
b allele is recessive and determines brown if
homozygous.
E allele at second gene has no affect on coat color.
e allele is recessive and if homozygous hides
effects of black or brown alleles.
-BBEE (black pure breeding) X bbee (golden pure
breeding) produce BbEe black F1 offspring.
-BbEe X BbEe produce 9 black (B_E_) for every 3 brown
(bbE_), and 4 gold (__ee).
9:3:4 is a telltale ratio of recessive epistasis.
25
Lab Retrievers and Epistasis
13
1/21/2016
Lab Retrievers and Epistasis
Black “B” is dominate to Chocolate “b”
A second gene E will mask the Black/Choc Gene if homozygous recessive “ee”
producing yellow lab
Lab Retrievers and Epistasis
Black “B” is dominate to Chocolate “b”
A second gene E will mask the Black/Choc Gene if homozygous recessive “ee”
producing yellow lab
bbEE or bbEe
BBEE BbEE
BBEe BbEe
BBee
Bbee
bbee
14
1/21/2016
9:3:4 recessive epistasis
30
15
1/21/2016
Summer Squash- dominant epistasis
Copyright © 2010 Pearson Education, Inc.
Any “B” white
12:3:1 Dominant Epistasis
32
16
1/21/2016
Complementary gene action
Two different genes work together to
produce a phenotype.
9:7 ratio is a phenotypic signature of
complementary gene interaction where
dominant alleles of two genes act
together to produce a trait while other
three genotypic classes do not.
33
9:7
34
17
1/21/2016
35
36
18
1/21/2016
Complementation - different homozygous recessive mutations
that produce the same mutant phenotype (e.g., wingless)
produce wildtype (non-mutant) when crossed.
Complementation will not occur if the mutations are in the
same gene.
37
Complementation Analysis (Two genes or one gene)
Two homozygous
recessive flies
Two homozygous recessive flies
“Linked genes! 1x1 Punnett”
Effectively
Homozygous
mutant
Normal wild type progeny if
Cross was with two genes;
Progeny have wildtype alleles
for both genes
Copyright © 2010 Pearson Education, Inc.
19
1/21/2016
The left Side of Previous Slide
Each can make only one gamete:
left individual
+ means wildtype
m a+ x
right individual
+mb
ma+mb+
“heterozygotes” +ma or +mb
will not produce wingless mutant
39
The Right Side of Previous Slide
Each can make only one gamete:
+ means wildtype
mamb++
left individual
right individual
ma+ x mb+
Effectively
Homozygous
mutant
40
20
1/21/2016
One gene may contribute to several
visible characteristics
Pleiotropy – single gene determines more than one
distinct and seemingly unrelated characteristic
Some alleles may cause lethality.
Type of pleiotropy where alleles produce a visible
phenotype and affect viability
Alleles that affect viability often produce deviations
from a 1:2:1 genoptypic and 3:1 phenotypic ratio
predicted by Mendel’s Laws.
41
a. Inbred agouti X yellow
yields 1:1 agouti:yellow
Yellow must be AYA
and AY is dominant to A
b. Yellow x yellow mice
do not breed true.
AY is a recessive lethal.
AYAY die in utero and do
not show up as
progeny
42
21
1/21/2016
X-linked Genes
Figure 4-10
Copyright © 2010 Pearson Education, Inc.
w+ is wildtype or red
44
22
1/21/2016
Table 4-2
Copyright © 2010 Pearson Education, Inc.
X and Y linked traits in humans are
identified by pedigree analysis.
•
X-linked traits exhibit five characteristics
seen in pedigrees.
1.
2.
3.
4.
5.
Trait appears in more males than females.
Mutation and trait never pass from father to
son.
Affected male does pass X-linked mutation
to all daughters, who are heterozygous
carriers.
Trait often skips a generation.
Trait only appears in successive generations
if sister of an affected male is a carrier. If
46
so, one half of her sons will show trait.
23
1/21/2016
Figure 4-12
Copyright © 2010 Pearson Education, Inc.
Pedigree of colorblindness (X-linked)assign phenotypes and genotypes
48
24
1/21/2016
49
50
25
1/21/2016
51
Extranuclear Inheritance
•How genetic transmission revealed and explained
non-Mendelian patterns of inheritance
•Mitochondria and chloroplasts
•Examples of mutations in mitochondrial DNA that
affect human health
•Maternal effect
52
26
1/21/2016
Mitochondrial and chloroplasts are organelles
of energy conversion that carry their own DNA
•Chloroplasts – capture solar energy and store it in
carbohydrates
•Mitochondria – release energy from nutrients and
convert it to ATP
53
Origin and evolution of organelle
genomes: molecular evidence
• Endosymbiotic theory
– Mitochondria and chloroplasts originated more
than a billion years ago.
– Ancient precursors of eukaryotic cells engulfed
bacteria and established symbiotic relationship.
– Molecular evidence
• Both chloroplasts and mitochondria have own
DNA
• mtDNA and cpDNA are not organized into
nucleosomes by histones, similar to bacteria.
• Mitochondrial genomes use N-formyl methionine
and tRNAfmet in translation…just like bacteria!
27
1/21/2016
Four-o’clocks- Example of maternal
inheritance
Copyright © 2010 Pearson Education, Inc.
Yeast! – Mitochondrial Inheritance
Copyright © 2010 Pearson Education, Inc.
28
1/21/2016
•
Maternal
inheritance of
Xenopus mtDNA
Purified mtDNA
from two species
Hybridization only
to probes from
same species
F1 hybrids retain
only mtDNA from
mother.
•
•
•
mtDNA – at the gene level
•
•
16.5 kb in length
Carries 37 genes
•
•
•
•
13 proteins required for
cellular respiration
22 tRNA genes
2 genes for large and
small rRNAs
Compact gene
arrangement
•
•
No introns
Genes abut or slightly
overlap.
29
1/21/2016
Criteria for a mitochondrial inherited
disorder
• Maternal inheritance pattern- not Mendel
• Disorder is due to deficiency in
bioenergetics of the mitochondria
• Genetic mutation identified in at least one
mitochondrial gene
16-59
Cells can contain one type or a mixture
of organelle genomes.
• Heteroplasmic – cells contain a mixture of
organelle genomes
– Mitotic products may contain one type, a
mixture of types, or the second type.
• Homoplasmic – cells contain one type of
organelle DNA
– Mitotic products contain same type, except for
rare mutation.
16-60
30
1/21/2016
LHON- Leber’s hereditary optic
neuropathy
Mitotic segregation produces an uneven
distribution of organelle genes in
heteroplasmic cells.
• Women with heteroplasmic LHON mutation
– Some ova may carry few mitochondria with LHON
mutation and large number of wild-type.
– Other ova may carry mainly mitochondrial with
LHON mutation and few wild-type.
– Consequence of heteroplasmy after fertilization
• Some cells produce tissues with normal ATP
production and others with low production.
• If low production cells are in optic nerve, LHON
16-62
results.
31
1/21/2016
•
Individuals with
certain rare diseases
of the nervous
system are
heteroplasmic.
•
•
MERRF
Uncontrolled jerking,
muscle weakness,
deafness, heart
problems, kidney
problems,
progressive dementia
MERRF
32
1/21/2016
Mitochondrial inheritance in identical twins
• Mitochondrial genomes not same in twins
but nuclear genomes are identical
– Symptoms of neurodegenerative diseases or
other mutations may manifest in one twin, but
not other.
– In a heteroplasmic mother, chance of
phenotype of offspring depends on both
partitioning of mutant mtDNA after fertilization,
and tissue that receives mutation during
development.
16-65
Maternal effect (aka maternal influence)
• Nuclear genes of female gamete are
transcribed, and the gene products
accumulate in egg cytoplasm.
• After fertilization, the gene products are
partitioned to newly formed cells and can
influence gene function during early
development.
16-66
33
1/21/2016
Maternal effect- meal moth example
Copyright © 2010 Pearson Education, Inc.
34