Transcript Modification of Mendel

Alterations to Mendel
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Incomplete or partial dominance
Codominance
Multiple alleles
Lethal alleles
Gene interactions & multiple genes
Sex-linked, sex-limited, & sex-influenced
Effect of environment
Extranuclear inheritance
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Multiple genes
• Sometimes a phenotype is controlled by more
than one gene
– Different from multiple alleles of same gene!!
• Gene products don’t necessarily directly interact.
– Genes may code for enzymes in a pathway
– Cascade of gene during development
• Epistasis: a gene (or gene pair) masks or modifies
the expression of another gene (or gene pair).
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Epistasis: gene interaction that perturbs
normal Mendelian ratios
• Example: interaction between two genes in the
pathway for pigment production, C and P
– C, P = dominant; c, p = recessive.
– Because both genes are needed, if individual is
homozygous recessive for either gene, no color.
• CcPp, all colored in F1
• CcPp x CcPp
9:7 phenotypic ratio
– Do the Punnett square and see
– Independent assortment still applies
– Various interactions produce different ratios.
Epistasis example: Bombay phenotype
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In the ABO blood groups,
A and B are codominant.
How can the person in
this pedigree be type O
(IO IO)?
Epistasis example: explanation
A second gene, Ih codes for the base
sugar chain to which the A and B
sugars are added. A rare mutation Ih
Ih prevents proper formation so that
the A and B sugars cannot be added
even though the enzyme for doing
that is being made. (Diagram next
slide)
A second gene is masking the normal
phenotype.
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Molecular explanation
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Complementation
•Several different genes may contribute to phenotype.
•How can you tell whether a phenotype results from
one gene or from several?
•Create several mutants with the same phenotype.
•Perform complementation tests:
Cross different mutants. If mutations are in different
genes, offspring will have one good copy of each gene,
restoring WT phenotype: the mutants complement.
If offspring show the mutant phenotype, mutation is in
same gene.
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http://www.hort.purdue.edu/rhodcv/hort640c/proline/pr00003.htm
Complementation example
•Example: bacteria
unable to make the
amino acid proline.
proB mutants: known mutations in the proB gene.
proA mutants: have mutations in the proA gene, etc.
In which proline gene does “pro-53” have a mutation?
To find out, Create merozygotes.
These are bacteria that have two copies of the genes of
interest (bacteria normally have only one of each).
“Cross” pro-53 with each of the known mutants.
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Complementation crosses
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The unknown mutant (pro-53) is “crossed” with each of
the other types of mutants. Does the cross result in a
“cure” (the bacterium can now make proline) or is it still
defective?
In this cross, DNA
from a proA- mutant is
added to the pro-53
bacterium.
The presence of this DNA is unable to rescue pro-53
(does not complement), because the mutation is in
the SAME gene. The pro-53 must be a proA mutant.
The other crosses
pro-53 said to be in same complementation
group as other pro-A mutants.
What happens when pro-53 is crossed with a
proB mutant?
The added DNA cures pro-53
because now it has good copies
of all 3 genes: a+ b+ c+
Do a cross with a
proC mutant.
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The sex chromosomes
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• The rest of the chromosomes are autosomes.
– Sex chromosomes determine sex of individual.
• X and Y differ in size, X much bigger in humans
– But still synapse during meiosis, so still a pair
• In humans, fruit flies, XX = female; XY = male.
• In several other organisms, other combinations
of sex chromosomes determine sex.
• Because there are genes on sex chromosomes,
inheritance of certain traits can be sex-linked.
Sex linked, limited, & influenced
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• Sex linked inheritance is when the allele is
present on a sex chromosome (usually X).
• Sex limited: when other genetic factors restrict
expression to one sex
– Bulls don’t give milk.
• Sex influenced: other genetic factors modulate
expression. Example: pattern baldness
– Females must be homozygous recessive for trait
– Even then, hormonal factors restrict expression.
Environmental factors
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• Expression of genes is affected by genetic
background (internal environment) but also by
the external environment.
• Penetrance vs. Expressivity
– Penetrance refers to percentage of individuals in a
population that show the trait to some extent.
• 6 fingers is a dominant trait, but…
– Expressivity: the degree to which the trait is
expressed within an individual.
External environment
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• Numerous examples in other organisms, e.g. sex
determination in turtles and crocodiles.
• Temperature effects
– Conditional mutations, especially temperature
sensitive mutations. Permissive vs. restrictive.
– Himalayan rabbit, Siamese cat
– Lethal genes in microbes
• Growth and development
– Various human diseases, strike at various times of
development. E.g. Huntington disease.
www.tcainc.org/photos/ farpoint/saavik1.jpg
Mitochondrial Inheritance
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Endosymbiont hypothesis: mitochondria descended from
endosymbiotic bacteria.
Outer membrane separates organelle from
cytoplasm. Inner membrane site of ATP synthesis.
Inner and outer membranes analagous to Gram
negative bacteria.
Mitochondria have their own
DNA, ribosomes, tRNA (all
bacteria-like) and replicate
independently of cell cycle.
www.protein-ms.de/ RES/Mito/mito.htm
Mitochondrial Inheritance-2
• Mitochondria well integrated into cell
– Some genes for structure & function of the
mitochondrion are found in the nucleus.
– Not a completely independent entity.
• Mutations in Mt DNA cause genetic diseases
which reflect function of mitochondria
– Major function: ATP generation
– Diseases feature breakdown of function in tissues
requiring high levels of ATP
• Muscle and nerve tissue disorders
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Mitochondrial inheritance is maternal
• During meiosis in females,
cell division is asymmetric
with most of the cytoplasm
including mitochondria
going into the eventual
ovum.
• Spermatozoa are DNA
delivery devices with little
cytoplasm.
http://www.ucalgary.ca/UofC/eduweb/virtualembryo/PageMill_Images/image145.gif
yalenewhavenhealth.org/ library/healthguide/en...
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