Introduction to Genetics
Reading: Freeman, Chapter 13 (read twice, do
all the questions at the back of the chapter),
also Chapter 12 (to review meiosis, mostly)
Information
Genetics is, quite simply, the study of the
process by which information is transmitted
from one generation of living things to the
next.
Every living thing is organized via coded
information, called its genetic material.
Reproduction involves duplication and
transmission of an organisms genetic
material.
WHAT IS A GENE?
A gene is an information entity. It is a sequence of
DNA that codes for a single genetic instruction.
Usually, this instruction is the sequence of a protein, but a
gene may also serve to activate or deactivate other genes, in
a cell, or in neighboring cells.
Every aspect of our species is constructed based on
information encoded in genes.
The genes themselves do very little, they are information
storage molecules. It is the cytological machinery of our cells,
passed from one generation to the next, that translate these
instructions into a living organism.
The effects of every gene depend both upon other
genes, and upon the environment.
What is an allele?
• An allele is ONE variant of a gene. Many genes have two,
several, or many different variants of the same basic genetic
information.
• Some alleles are minor differences that to not significantly
affect the organism, others cause profound changes.
Example:
• Nucleotide substitutions in the third codon position
often produces no change at all, because they code
for the same transfer RNA and thus the same protein
is produced.
• In humans…CCU CCA does not cause a change,
both triplets code for proline.
• Other substitutions may produce profound effects,
sickle cell anemia is caused by a single nucleotide
substitution: GAG GUG changes normal
hemoglobin to hemoglobin that “sickles” under low
oxygen concentrations.
Prokaryotes, which include the archaea and
bacteria, are the simplest, oldest, and most
common organisms on the planet.
A typical prokaryote has a much smaller genome
than a typical eukaryote.
Nearly always, it is in the form of a simple loop of
DNA (with associated proteins).
This loop is attached to the cell membrane.
Even though the structure simple, there is a lot of
DNA in a single bacterium. .…
Stretched out, the DNA in an E. coli would be 500
times longer than the cell itself.
Prokaryotes do not have sexual reproduction,
though they have several forms of gene
exchange.
These include swapping plasmids
• The various genes, about 1200 in a typical bacterium,
are arranged along the length of the chromosome,
like beads on a string.
– There is no particular functional grouping to their order, it is
mostly evolutionary chance that determines their location
• In prokaryotes, the DNA loop replicates before
fission, with both loops still attached to the cell
membrane
• During fission, as the cell membrane splits in two,
one loop of DNA ends up in each new “daughter cell”
Thanks to/stolen from fig.cox.miami.edu
Most eukaryotes have several orders of magnitude more
DNA than a typical prokaryote.
Like prokaryotes, eukaryote genes are arranged along the length
of a chromosome like beads on a string.
There is no particular functional reason for their location,
either within a chromosome, or with respect to what
chromosome they are on, it is mostly an evolutionary
accident.
Eukaryote DNA (except plastid DNA, which is very
similar to bacterial DNA because of its evolutionary
origin) is usually linear, not circular.
These strands are long, and extended (thus, invisible to
microscopes) during the normal life of the cell.
These linear strands of DNA are called chromosomes and
packed into a nucleus (or nuclei, in some cases).
In multicellular eukarotes, every cell has the same
DNA, though in any given cell, only a fraction of the
genes are active, others are permanently “turned off”
The increased amount of DNA
necessitates a means of condensing
these long strands into compact
structures that can be sorted into
separate daughter cells during cell
division.
Histones are important and very
evolutionarily conservative proteins.
Loops of DNA are wrapped around
one histone (like thread around a
spool), and locked in by a second,
forming a structure called a
nucleosome.
These structures further
supercoil into a condensed
configuration, to form the
familiar shapes that scientists
have viewed under light
microscopes.
Thank you/stolen from www.geneticengineering.org
Mitosis
• Mitosis, the duplication of the
genetic material within a eukaryote
cell, is worth mentioning here
because of what it IS and what it IS
NOT. Do not bother
– A cell gives rise to two, smaller but to memorize
genetically identical copies of itself. the phases of
– It IS a duplication of the genetic mitosis/meiosis,
complement of a eukaryote cell. Since
it is usually followed by cell division, I do not care
it can lead to growth, in a multicellular
organism, or asexual reproduction, in
a single-celled organism.
– It IS NOT a means of producing
gametes. In sexual organisms, mitosis
is peripheral to sexual reproduction, it
serves to give rise to cell types which
ultimately “kill themselves off” by
splitting and splitting again, into four,
very different, cells.
Sexual Reproduction
• Sexual reproduction is a particular type of reproduction, a sharing of
genetic material, to form an individual with equal contributions from two
separate parents.
• This involves:
– The formation of haploid sex cells, called gametes, from a diploid cell, a
process called Meiosis.
– Syngamy (or, fertilization), a combination of genetic information from two
separate cells to form a diploid cell, called a zygote.
• Gametes usually, but not always, come from separate parents: female
produces an egg and male produces sperm. (In some organisms, the
haploid phase of the life cycle is multicellular, and haploid individuals
simply grow together during the process of syngamy.)
• Both gametes are haploid, the resulting zygote is diploid.
• Sex probably evolved as a means of producing variable offspring in the
face of an uncertain future, though its evolutionary origins are obscure.
• It is virtually ubiquitous among eukaryotes, though many can produce
sexually or asexually.
• It has the potential to produce enormously variable sets of genetic
information, something that can be crucial to the survival of a species.
Diploidy
• Diploidy is the state of having two copies of every
single gene-like pairs of shoes, pairs of gloves, pairs
of stereo speakers.
– Humans, and many of the organisms with which
we are familiar (flies, zebras, potatoes), are
diploid.
– We have two copies of every gene in our bodies.
– For many genes, these copies are identical
matches (they are homozygous).
– For others, there are subtle differences between
the two copies (they are heterozygous).
• Not all organisms are diploid as adults, some are
haploid.
– For sexual reproduction to occur, there must be
both a diploid and a haploid phase of the life cycle.
Meiosis
• Meiosis is that process by which a single diploid cell gives rise to four,
genetically different, haploid cells.
• It works like this (forget the phases):
– The diploid progenitor duplicates its genetic material…thus, every
chromosome is composed of two, identical, chromatids, joined at the
centromere (this happens before meiosis starts)
– Each chromosome finds its match, to form “matching pairs” of homologous
chromosomes. This process, which occurs during the first of the two
meiotic divisions, is unique to meiosis, it does not occur during mitosis.
– Four strands (two homologous chromosomes, composed of two identical
strands each) cluster in structures sometimes called tetrads, along a plane
in the center of the dividing cell. A process called “crossing over” may
occur at this time.
• First division, homologous chromosomes separate.
– Spindle fibers drag them to opposite poles of the cell. The cell then
divides. Which chromosome ends up where is completely random and
is not influenced by the fate of the other chromosomes around it. The cell
then divides.
• Second division, chromatids separate.
- Spindle fibers drag them to opposite poles of the cell. The cell then divides.
• This gives you four, genetically different, daughter cells from a single
parent.
www.biologycorner.com
The ancestral sexual species
Meiosis results in 4 daughter cells Probably had a life cycle similar
Daughter cells are haploid
Daughter cells have unique combinations of chromosomes To that pictured above.
Daughter cells do not have homologous pairs
Meiosis creates gametes (sperm and eggs)
Meiosis ensures variability in offspring
Errors in • Errors in meiosis have the potential to
Meiosis produce unusual phenotypes in the
offspring.
• The most common meiotic error is
nondisjunction, where an entire
homologous pair of chromosomes migrates
to the pole of a cell, without splitting.
• If this happens to a single pair, it causes
either a trisomy, or a monosomy, in the
resulting offspring.
• If it happens to the entire genome, it can
produce triploid or even tetraploid
offspring.
• The human condition of Down’s syndrome
results from a trisomy at chromosome 21, a
trisomy at chromosome 18, 13, or the sex
chromosomes (23), is also survivable. In
humans, trisomies for other chromosomes
are not usually viable.
• In other organisms, triploids and tetraploids
may be viable.
How Meiosis, and Sex, Produce Variation
• Meiosis starts with a single diploid cell with two
redundant sets of DNA, and produces four haploid cells,
each with a single set of DNA.
• These four cells all have DIFFERENT sets of alleles,
although they have the same genes (one copy of each,
not two).
• Meiosis produces variation in two ways.
– By randomly selecting one, or the other, chromosome from a
diploid set, to form a haploid set, an enormous number of
potential gametes arise. In an organism with 23 pairs of
chromosomes, for instance, 223 potential gametes can be
formed this way. This phenomenon is called assortment.
• By the process of recombination, which is a result of
crossing over, new combinations of alleles on
chromosomes may arise.
• Crossing over is a cytological phenomenon that
occurs during the first of the two meiotic divisions.
– Two strands of DNA from complimentary chromosomes
cross over each other, and a break forms.
– The break is quickly repaired, switching stretches of DNA
among the two compliments to create two new
chromosomes.
– A pair of chromosomes can cross over once, several
times, or not at all. The farther apart two genes are on a
chromosome, the more likely it is that crossing over will
create recombination between the two of them.
• Crossing over creates new combinations of alleles
on chromosomes, and permits favorable alleles to
combine together on the same chromosome.
• The genetic result is called recombination.
•When geneticists speak about
genes, they prefer to use the
word locus. The two are virtual
synonyms, but locus means
location, and it refers to the
place where variation can occur.
Using the word gene
emphasizes its information
content.
•Thus, as you might be able to
intuit from the diagram to the
left, the more distant the loci
(plural), the more likely it is for
a particular recombination event
to switch them between
chromosomes.
The Patterns Inherent in Mendelian Genetics Result from the
Nature of the Eukaryote Genome, and the Events of Meiosis
• The preceding information explains the cytological and evolutionary reasons why
genetics works the way it does in eukaryotes.
• Meiosis does not produce new genes, or new alleles
• The genetics that follow have their cytological underpinnings in the events of meiosis.
• It does, however, create new combinations of chromosomes, and new combinations
of alleles on chromosomes
• For example:
– Segregation is the process by which a gamete comes to have only one of the
two alleles its parent possesses, for every gene. It is random, and it occurs
because of the separation of homologous chromosomes during the first meiotic
division.
– Assortment accounts for the fact that most eukaryotes possess many pairs of
chromosomes, it is segregation at two or many loci simultaneously. Assortment
is responsible for the variation in gametes created by the random selection of
chromosome from each pair into gametes..
• Example: via assortment alone a human with 23 pairs of chromosomes can produce 223 potential
gametes, far more than every person who has ever lived.
• When genes are on separate chromosomes, it is said that they assort
independently. When they are on the same chromosome, they tend to get
passed on as a unit, which can only be broken up by recombination, this is
called linkage.
Variation is ubiquitous, all organisms
exhibit SOME variation
• Look around the classroom and you will immediately notice a
great deal of variation among members of this class.
• Some of this variation is morphological: hair color, height, eye
color, etc..
• Some is behavioral: preference for certain foods, knowledge of
languages, choice of clothing, etc..
– Other organisms; crayfish, salamanders, scorpions, exhibit similar
amounts of variation (though we are not as sensitive to it at first
glance).
• For centuries, biologists have sought an explanation for this
variation.
• Much of this variation has its basis in our genes, a fact that is
of tremendous biological significance.
Variation within the
White-cheeked Rosella
The White-cheeked Rosella
is made up of four varieties,
each with its own distinct
color combination and
markings.
The diagram shows where
these varieties are found.
Question-Based upon this
information alone, can you
Tell whether the variation
is genetic, environmental,
Stolen from-www.environment.gov.au or both?
Types of Variation
• Attributes, or qualitative variables, can be scored,
but not fall into a continuum.
– Examples: human eye color, political party, blood type,
gender, etc..
• Quantitative, or measurable, variables fall along
a measurable axis, and can be measured to
observe their place relative to others.
• Discontinuous measurable variables: fall into
discrete intervals. Examples: shoe size, number
of mates, number of arrests for drunk driving, etc..
• Continuous measurable variables do not fall
into discrete intervals, they exist along a
continuum. Examples: height, weight, age, etc..
Distributions of Values
• A group of individuals has a distribution of
values for every quantitative variable. This
reflects the number of individuals possessing
each value for the trait.
• The group of individuals in question is the
statistical population, the population has a
distribution of values for the variable.
• These distributions are frequently expressed
as a histogram: the range of values for the
category is broken into intervals, and the
number of individuals within that interval is
expressed as the height of a bar.
A Histogram
Types of Distributions
• Populations of actual organisms exhibit a
great variety of distributions for different
measurable variables.
• Some common distributions are:
– Normal
– Bimodal
– Multimodal
• Distributions may also be skewed, or exhibit
kurtosis.
Normal Distribution
A Skewed Distribution
Bimodal Distribution
Mean, Median, Variance, etc.
• The distribution of numerical values can be
described by several statistics:
• (Arithmetic) Mean: the average: x=Sx/N
• Median: The value with the same number of
observations preceding it, and following it
• Variance: s2 =the variability of values in the data
set, their tendency to depart from the mean
2
s2=(S(x-x) /N-1 )
• Standard Deviation: s=the square root of the
variance.
Dominance
• As you remember, diploid organisms have two sets of
redundant genetic information-two copies of every
gene.
– An individual is homozygous at a locus if they have two
alleles for a gene, and heterozygous at that locus if they
have different copies.
• Dominant alleles mask the effect of a recessive allele
at that locus, they are expressed in the homozygous
or the heterozygous state.
• Recessive alleles are only expressed in the
homozygous state.
By convention, we usually use a capital letter to
designate the dominant allele, and the lower case of
the same letter to designate the recessive allele.
• Example: Alleles for albino coloration
media.ebaumsworld.com/..
in many animals result from recessive
alleles.
– It is usually a defective protein that inhibits
the metabolic pathway associated with the
production of a protein, or (more often),
inhibits its placement in the target tissue.
– In most cases, even one copy of a non-
defective gene at this locus restores the
pathway.
• Thus, for albino coat color in mice,
Individuals with either one or two copies
A (dominant) allele have brown fur.
• Therefore AA and Aa have brown fur.
Note that Aa individuals can pass on the
a allele, even though they do not
express it themselves, they are carriers.
• Individuals with two copies of the albino
allele, aa, have white fur.
Some Alleles of Medical Interest
• Because, when rare, recessive alleles are usually in the
heterozygous state, and not subject to natural selection, human
populations harbor quite a few harmful, recessive alleles at low
frequencies.
– For instance, a rare, autosomal recessive allele on chromosome 7 disrupts
the normal migration of neurons, leading to an abnormally thick and smooth
cerebral cortex, and reduced cerebellum, hippocampus, and brainstem
causing a condition called lissencephaly.
– It is typical of these conditions for an affected individual to be born to
normal parents.
• Dominant alleles, by contrast, are generally manifested in the
parents.
• For instance, ectrodactly, a condition where the affected individual
has severely deformed digits, is caused by a dominant allele.
• It runs in families, conspicuously, and was passed from the
famous circus performer, Grady Stiles Junior, to one of his
offspring.
Typical manifestation of
lissencephaly
Grady Stiles Junior, as a
young man
Codominance
• Codominance (sometimes called incomplete
dominance) is the allelic interaction where, in the
heterozygous state, both alleles are expressed (for
attributes), or the heterozygote is in between the
phenotypes of the homozygous individuals for those
alleles (in the case of measurable characters).
– Thus, the heterozygote has a unique phenotype.
• For example, in chickens, black feather color is
codominant with white feather color. Heterozygous
chickens have black and white feathers in a
checkered pattern.
• FBFB is black, FWFW is white, and FWFB is checkered.
Note that the notation uses superscripts, which
makes it clear that neither allele is dominant.
Human Blood Type
• The human ABO locus has three loci, which exhibit both
dominance and codominance.
• Human blood types are encoded by a single locus with three
alleles: IA, IB, and i0.
• IA and IB code for two different proteins, cell surface antigen A,
or antigen B. i0 codes for the lack of that particular protein.
• Since we are diploid, we have a blood type, a phenotype, that
depends upon the proteins on the surface of our blood cells.
• IA IA and IA i0 are A, IBIB and IB i0 are B, i0i0 is O.
• IA and IB are therefore CODOMINANT with respect to each
other, and both are DOMINANT with respect to i0.
• Most traits are not coded by a single gene…the
Rh+/Rh- status of an individual is coded by at least
two loci, RhD and RhCE..
• Having a dominant allele at either of these loci
makes a person Rh+, having recessive alleles at
all the Rh loci makes a person Rh-
ce d/ce d Negative
CE D/ce d Positive
CE d/CE d Positive
ce D/ce d Positive
CE d/CE D Positive
CE D/CE D Positive
Phenotype vs. Genotype
• An organism’s PHENOTYPE is its
observable characteristics.
• An organism’s GENOTYPE is its genetic
composition of alleles.
• Thus, an organism heterozygous for a
recessive allele, such as albinism, would
exhibit the dominant trait, yet would
possess the heterozygous genotype.
How Many Loci are There?
– Bacteria have about 1,200 genes
– Yeast have about 5,000,
– Drosophila melanogaster have about 10,000
– Human beings have approximately 29,000.
• Do all loci have multiple alleles?
– No, only a small percentage of loci have multiple
alleles, perhaps 1-5% or less, depending upon the
species.
Genes Interact with the Environment
to Produce a Phenotype
• A gene does not act alone, it gives instructions to
other aspects of the developing organism, or it
produces a protein that is put to use in various
metabolic pathways and processes.
– Nearly every gene interacts with the environment to
some extent. Sometimes the contribution of the
environment is small, sometimes it is very significant.
• This is no mere nature vs. nurture dichotomy, it is a
complicated interaction and interplay.
Geographic Variation in Yarrow-A Norm
of Reaction
• The norm of reaction describes the pattern of phenotypic
expression of a particular genotype across different
environments.
• For example, in yarrow, tall plants grow at low elevation
roadsides, and much shorter plants grow in the mountains.
• A naive researcher might conclude that the mountain plants
simply had genes for growing short, or that the cold
conditions in the mountain dwarfed them.
• Grown under identical conditions, at low elevations, the
mountain plants grow a little taller, but not nearly as tall as
low-elevation plants.
• Grown under identical conditions, in the mountains, the low-
elevation plants grow VERY small, or die.
In fact, the mountain plants have
a variety of alleles at different
loci coding for aspects of
dealing with cold winters and
short summers, but the cost of
these alleles is reduced growth
under friendlier conditions.
Differently adapted local
varieties of a species are called
ecotypes. An ecotype that
performs well in one situation
might perform very poorly in
another environment.
Genetics Problem
• A chicken with black feathers is mated to a chicken with
white feathers.
– (by convention, this generation is called the P1)
• This cross produces 9 offspring, all of which have
checkered, black and white feathers.
– (by convention, this generation is called the F1)
• Two of these offspring (the F1) are allowed to mate and
produce offspring of their own.
• Diagram the cross, including the
– genotypes of the parents
– the genotypes of the GAMETES each parent produces
– the genotypes of the F1 offspring
– and the gametes the F1 can produce
– and the genotypes of the various F2 offspring.
• Predict the phenotypic composition of this next generation,
the F2.
• Answer.
• Start by listing the genotypes of the P1s, this is part of the answer, and
you will get nowhere if you skip right to a Punnet square.
– The P1s are FwFw and Fb Fb
• The white parent can produce one type of gamete, Fw, the black parent
can produce one type of gamete, Fb. Note, gametes are always haploid.
• The F1 are all FwFb, this is the only possible genotype, given the two
parents. Note, adults are always diploid.
• These F1 can produce two types of gametes, Fw and Fb.
• To produce an F2, these two gametes can unite in four possible ways.
• The male F1 parent can produce a Fw or a Fb
• The female F1 parent can produce a Fw or a Fb
• This gives:
– Fw from the male parent x Fw from the female-white chicken
– Fb from the male parent x Fb from the female-black chicken
– Fw from the male parent x Fb from the female-checkered
– Fb from the male parent and Fw from the female-checkered
• The colors in the offspring are ¼ black, ¼ white, ½ checkered.
– If you answered ¼ to ¾, you should consider that this is a codominant system.
Much of what we know about genes was
first discovered by Gregor Mendel
• Gregor Mendel was one of those rare historical geniuses who
seems to exist in a vacuum (he didn’t he lived at a monestery
with a tradition of science). His work was not well known until
after his death.
• He conducted experiments on the garden pea, Pisum sativum,
a species that exhibits variation for several interesting
characters: pod color, seed color, flower color, height, etc..
These differ because of alleles at a single locus.
• Garden peas also produce a large number of offspring, a key to
Mendel’s success.
• Mendel was among the first scientists to think in quantitative,
rather than strictly qualitative terms.
Mendel’s Laws
• Through experiments, Mendel deduced some basic patterns.
• Inheritance is particulate: “particles” called genes carry the
information that makes parents tend to resemble their offspring.
– This was a huge departure from the previous scientific
paradigm, believed for centuries, that inheritance was
somehow carried in the blood and blended together every
generation.
• These “particles” segregate, so that individuals with two
particles produce gametes with only one particle, the law of
segregation.
• The “particles” for each gene segregate independently of each
other, the law of independent assortment.
– This law is, of course,not universal. It applies only to the special case
where genes are on separate chromosomes. It was not until decades
later that the relationship between chromosomes, and Mendel’s particles,
was discovered.
A Classic Mendelian Experiment
• Two lines of garden peas have been grown separately for
a long time, they are called “true breeding” lines because
the parents always resemble the offspring. One line has
purple flowers and one line has white flowers. A parent is
chosen from each line. These are called the P1.
• When they are artificially crossed (garden peas normally
self-fertilize), the resulting offspring (called F1) are all
purple.
• Two individuals from the F1 are crossed.
• The resulting offspring (the F2) are 75% purple-flowered
and 25% white flowered. WHY?
• DIAGRAM THIS CROSS in a similar way to the way you
diagrammed the last one.
Questions:
• 1. What is the probability that any given
pollen grain from the white flowered line
contains an allele for white flowers?
• 2. How about a pollen grain from the F1?
• 3. What about a pollen grain from a white
individual taken from the F2?
Answers:
• 1. 1.0
• 2. .50
• 3. 1.0
Another Experiment
• One of F1 from the cross above is
mated to an individual from the white-
flowered line.
• DIAGRAM THIS CROSS
– What would be the phenotypic composition
of the resulting offspring?
– What would be the genotypic composition
of the resulting offspring?
Independent Assortment
• The segregation of alleles into gametes follows the laws of
probability: therefore an Aa individual would produce 50% A
gametes and 50% a gametes.
• If you consider two loci, with independent assortment, the
chance of a particular allelic genotype is a product of the
probabilities of the alleles at each locus.
– Ie., an AaBb individual would produce 25% AB gametes, .50 is the
probability of a A in the gamete, and .50 is the probability of B in the
gamete, .5 x .5 is .25
– An AaBbCc individual would produce 1/8 ABc gametes, for analogous
reasons.
• If genes are on different chromosomes, alleles assort
independently of each other. This is called independent
assortment. The chance of an allele at one locus being in a
particular gamete is independent for each locus.
• The number of potential, different, gametes a parent can
produce is equal to 2N, where N is the number of loci
assorting (do not count homozygous loci).
• Thus, a heterozygote for three loci: Aa Bb Cc could form
EIGHT different gametes:
• ABC, ABc, AbC, aBC, Abc, aBc, abC, abc
– By contrast, AA BB Cc can form only two different gametes, ABc
and ABC, because only one locus is assorting
• For N independently assorting loci, there are 2N
different gametes that can be created. If they are truly
assorting independently, they will be present in equal
numbers.
– Departures from independent assortment are most often caused
by LINKAGE, when two loci are close to each other on the
same chromosome.
• Linkage causes certain combinations of alleles to be
over-represented in the gametes.
Sample Problem
• Albinism is a condition that results from the lack of
normal pigmentation. In humans, individuals with two
recessive alleles at the ALBINO locus are albino,
• therefore AA=pigmented
• Aa=pigmented
• aa=albino
• Attached earlobes result from two recessive alleles at the
EARLOBE locus.
• therefore EE=non-attached earlobes
• Ee=non-attached earlobes
• ee=attached earlobes
• Imagine an albino man with non-attached earlobes marries
a pigmented woman with attached earlobes.
• They have 23 children, none of them twins.
• All of their children are pigmented with non-attached
earlobes.
• QUESTIONS;
• What is the most likely genotype of the man?
• What is the most likely genotype of the woman?
• What alleles for pigmentation will HIS gametes carry?
• What alleles for pigmentation will HER gametes carry?
• What alleles for earlobes will HIS gametes carry?
• What alleles for earlobes will HER gametes carry?
• What are the possible GENOTYPES of their offspring?
SOLUTION:
• Since all their offspring are pigmented with non-attached
earlobes:
• The man is almost certainly aaEE
• The woman is almost certainly AAee
• (otherwise, at least one of the children would have been
albino, had attached earlobes, or both )
• Their offspring are all AaEe.
• The man’s gametes carry a SINGLE a allele for
pigmentation, and a single E allele for earlobes.
• The woman’s gametes carry a SINGLE A allele for
pigmentation and a single e allele for earlobes.
• (Based on their phenotypes, you cannot
distinguish parental phenotypes aaEe from
aaEE, or AAee from Aaee, but since none
of their children exhibited the recessive
phenotype, it is a pretty good bet the parents
were both homozygous at both loci).
Now, imagine two of their children
interbred and had a child.
• How many types of gametes can their children
produce?
• What would be the possible GENOTYPES and
PHENOTYPES of their offspring?
• Assuming independent assortment, what is the
probability that their first child will be an ALBINO
with ATTACHED EARLOBES?
SOLUTION:
• Their children, the F1generation, are HETEROZYGOUS at
TWO loci.
• They can produce FOUR different gametes:
• AE aE Ae ae
• Since the children have interbred with each other, their are
SIXTEEN possible combinations of male and female
gametes:
Punnet Square:
• male gametes
• AE aE Ae ae
• AE AAEE aAEE AAeE AaEe
• aE AaEE aaEE AaeE aaeE
• female gametes Ae AAEe AaEe AAee aAee
• ae AaEe aaEe Aaee aaee
• Note that there are only NINE different genotypes and
FOUR different phenotypes for the offspring, because
several combinations of male and female gametes give the
same genotype, and several genotypes give the same
phenotype.
• The chance their first child will be albino with
attached earlobes is 1/16, since only one of sixteen
combinations, ae vs. ae, gives the aaee genotype
which results in the albino attached phenotype.
QUESTION
• The mother from the cross goes on the Jerry
Springer show for having an illicit affair with her
first born son. She claims to have given birth to
ANOTHER child, this one is normally pigmented
with attached earlobes. What are the potential
genotypes, and phenotypes, of that child?
• Assuming independent assortment, what is the
chance that a child from this type of union will be
albino with non-attached earlobes?
• Is that child her husband’s, or her son’s?
•
ANSWER: produce four
Remember, the F1 male (her son) can
gametes:
• AE, Ae, aE, ae
• She can produce one gamete, Ae
• therefore:
• male gametes
• AE aE Ae ae
• female gametes Ae AAEe AaEe AAee aAee
• Note that there are four potential genotypes, and TWO
potential phenotypes, pigmented with attached earlobes and
pigmented with non-attached earlobes, 50% chance of each.
• The child could be her son’s, but it couldn’t be her
husband’s.
Testing Independent Assortment
• A TEST CROSS is used to determine whether two
loci are linked.
• Cross two true-breeding parental lines, such as Sepia
vs. Black Drosophila melanogaster:
• se se BK BK x SE SE bk bk
• to create a heterozygous F1:
• SE se BK bk
• Now, INSTEAD of crossing the F1 to ITSELF,
cross it to a line which is HOMOZYGOUS for
RECESSIVE alleles at BOTH LOCI
Test Cross
• SE se BK bk x se se bk bk
• male gametes
• se bk
• SE BK SEse BKbk
• se BK sese BKbk
• female gametes SE bk SEse bkbk
• se bk sese bkbk
• Note that this cross yields FOUR different Genotypes,
each with a distinctive PHENOTYPE, they should be in
equal numbers.
Test Cross Ratios
• Eyes Body Expected Ratio
• Red Normal 1/4
• Sepia Normal 1/4
• Red Black 1/4
• Sepia Black 1/4
• If the two alleles are linked, the PARENTAL
phenotypes will be OVER-REPRESENTED.
The Chi-Square Test:
• The Chi-Square test is a good statistical tool to test a
hypothesis with distinct OBSERVED and
EXPECTED values.
• Imagine we did the cross above and counted 400
offspring. We observed the following numbers.
• Eyes Body Number Observed
• Red Normal 101
• Sepia Normal 99
• Red Black 106
• Sepia Black 94
This is how we would do a Chi-Square test:
• if the expected ratio is 1/4:1/4:1/4:1/4, we expect 100 flies
with each phenotype.
• Eyes Body Number Observed Number Expected
• Red Normal 101 100
• Sepia Normal 99 100
• Red Black 106 100
• Sepia Black 94 100
• The Chi-Square (Written c2) =S(O-E)2/E, is in index of
how far your observed numbers are from your expected
numbers.
• QUESTION; What is the Chi-Square value from the cross
above?
Answer:
• Eyes Body # Observed # Expected O-E (O-E)2/E
• Red Normal 101 100 1 .01
• Sepia Normal 99 100 1 .01
• Red Black 106 100 6 .36
• Sepia Black 94 100 6 .36
• S(O-E)2/E=.74
What the #@!?? Does this
Number Mean?
• The c2 value for any given test represents the
extent to which the observed values depart from
the expected values.
• The c2 distribution lists the probability of any
given set of observed values departing from the
expected values by chance, given the degrees of
freedom-degrees of freedom=N-1 where N=the
number of comparisons
• QUESTION: How many degrees of freedom were
there for the cross we just did?
• ANSWER: N-1=3 degrees of freedom.
• QUESTION: What is the probability that the
observed values from the cross above would depart
from the expected values to the extent that they did?
(see your lab manual, page 93)
• ANSWER: With three degrees of freedom, the probability
of departure is >.70. In other words, MOST data sets will
depart by that much, or more, even if the hypothesis that
generated the expected values is perfectly correct.
• Why?
• Because a certain amount of departure by random chance is
part of the essential, probabilistic nature of genetics.
• Why >.70?
• The table on page 93 gives a few rough benchmarks. For
example, at 3 degrees of freedom, 50% of data sets depart to
the extent that the c2 value is 2.37 or more (P<.50). 5%
depart to the extent that the c2 value is 7.81 or more
(P<.05).
Most scientists use an arbitrary criterion to determine
whether the departure of observed and expected values
was due to chance, or due to a flaw in the hypothesis
that generated the expected values to begin with.
• The arbitrary cutoff is P<.05. If there is less than a 5%
chance that the observed and expected values would depart
to the extent that they did by chance alone, than we say that
the hypothesis is falsified we reject it.
• Otherwise, we accept it (this does not mean we have proven
it, however, because an infinite number of hypotheses can
be concocted to generate the same data).
• QUESTION: For the cross above, do we accept, or reject
the hypothesis?
• What does this mean?
• ANSWER: Accept the hypothesis.
• The hypothesis that we used to generate the
expected values was independent
assortment.
• Since we cannot reject independent
assortment, this means that the genes are
not linked.
Linkage
• Linkage is the result of two loci being
located close together on the same
chromosome. It causes a departure from
independent assortment (thus, Mendel’s
second law is incorrect, but he didn’t know
about chromosomes).
• In crosses involving two loci, linkage
causes certain combinations of alleles to be
over-represented in an individual’s gametes.
Example of Linkage
• In Drosophila melanogaster, the recessive allele for the
sepia locus causes flies to have very dark colored eyes. The
recessive allele at the ebony locus causes the fly to have
very dark body color.
• A male from a true breeding line of sepia eyed-ebony
bodied flies is crossed to a female from a true breeding line
of red eyed, tan-bodied flies (the “wild type”).
• se se eb eb x SE SE EB EB
• to create a heterozygous F1: SE se EB eb
• Now, cross a female F1 to a male from the sepia-eyed,
ebony bodied, line.
• QUESTIONS: What is the phenotype of the F1?
• With no linkage, what is the expected proportion of sepia-
eyed, ebony-bodied flies?
Answer:
• The F1 are “Wild Type”
• With no linkage, the expected proportion of
sepia-eyed, ebony bodied flies is 25%.
Now, imagine we got this data
• Eyes Body Number Observed
• Red Normal 123
• Sepia Normal 77
• Sepia Ebony 119
• Red Ebony 81
Are the loci linked?
• Eyes Body # Observed # Expected O-E (O-E)2/E
• Red Normal 123 100 23 ?
• Sepia Normal 77 100 23 ?
• Sepia Ebony 119 100 19 ?
• Red Ebony 81 100 19 ?
• S(O-E)2/E=??
• Eyes Body # Observed # Expected O-E (O-E)2/E
• Red Normal 123 100 23 5.29
• Sepia Normal 77 100 23 5.29
• Sepia Ebony 119 100 19 3.61
• Red Ebony 81 100 19 3.61
• S(O-E)2/E=17.8
• The loci are linked.
• QUESTION: Why are there fewer SEPIA NORMAL
and RED EBONY?
• Answer: Linkage causes the GRANDPARENTAL
phenotypes to be over-represented in the progeny
from a test cross.
• MOM DAD
SE EB se eb
SE EB se eb
• Egg sperm
se eb
SE EB
• F1 SE EB
se eb
• gametes (without recombination)
SE EB
• gametes (with recombination)
se eb
se EB SE BE eb
Linkage Mapping
• You can tell how far apart loci are by the
proportion of the F2 from a test cross that are
recombinants. Simply take the number of
recombinants and divide by the total, and that
gives you r-the proportion of recombinants.
– For instance, for the cross we just did, the
recombinants were Red Ebony and Sepia Normal.
– Thus, r= (81+77)/400=.40
• Hint-the recombinants are the F2 that do not
resemble the grandparents.
• From r, you can get the distance between
loci. Simply multiply r by 100 and you get
the distance in map units (Morgans).
• Thus .40x 100=40 map units.
• Note that the more recombinants, the higher
r, and the farther they are away in map
units.
• Loci that are very close together are said to
be tightly linked, and produce few
recombinants.
This is a linkage map of sorgum, which was a
work in progress when I wrote this slide.
The linkage groups almost always turn out to be chromosomes
the genetic markers are loci that have been placed in order
by a comparison of their relative distances
(this is from the icrisat website)
An Interesting System, Heterostyly
in Primrose
• In Primula sp., an interesting genetic
system maintains two distinct phenotypes in
the population, and ensures the virtual
absence of intermediate phenotypes.
• It is called heterostyly, because each type of
flower is well adapted to cross with its
opposite, but unable to cross with itself.
• This system encourages outcrossing, which
can potentially maintain genetic diversity.
• The dominant, G allele codes for
short style (the female part of the
flower), which reaches to the middle
of the corolla tube, the recessive, g
allele codes for a longer style, which
reaches to the lip of the corolla.
• The dominant, A allele codes for
long anthers (the male part of the
flower), which reaches to the edge of
the corolla tube, the recessive, a
allele codes for short anthers, which
reach to the middle of the corolla
tube.
• The dominant P, allele codes for
“thrum” pollen, the recessive, p
allele codes for “pin” pollen, which
is much smaller.
• The three loci are very closely
linked-so that crossing over rarely
occurs
Thrum-left, pin-right
• In normal populations, only two
genotypes are present, GgAaPp, and
ggaapp
• The genotype ggaapp gives rise to the
“pin” phenotype, which has long styles,
short anthers, and pin pollen.
• The genotype GgAaPp gives rise to the
“thrum” phenotype, which has short
styles, long anthers, and thrum pollen.
• Even though other genotypes are
theoretically possible, a combination of
tight linkage, and the mechanical
impossibility of thrum x thrum crosses
keeps them from becoming common.
• Thrum x thrum crosses are impossible,
because thrum pollen cannot grow down
a short style.
• Pin x pin crosses are possible, but very
rare. Primula veris. Thrum is on
the left, pin is on the right
• Each form is adapted to transfer pollen to a
different part of the potential pollinator, thrums
transfer pollen to the waist, which can be
received by the styles of a pin flower.
• pins transfer it to the insects head….which can
be received by the style of a thrum flower.
• Rare crossing over events, in thrum flowers,
produce intermediate phenotypes, but these do
not do not produce many offspring of their own,
at least via animal pollinators.
Sex-Linkage
• Sex linkage is not really linkage.
• Sex linkage is the term for a locus being located on a
sex chromosome, such as the X chromosome in
humans or Drosophila.
• Sex linkage causes a unique combination of
inheritance.
• For instance, in humans, males receive only ONE
allele from each sex linked locus (from their mom).
• Recessive alleles are therefore automatically
expressed in the male, a state referred to as the
hemizygous condition.
• Homogametic sex: that sex containing two
like sex chromosomes. In most animal
species these are females (XX).
– Butterflies and Birds, ZZ males.
• Heterogametic sex: that sex containing two
different sex chromosomes In most animal
species these are XY males.
– Butterflies and birds, ZW females.
– Grasshopers have XO males.
• In ants, bees, and wasps, males are haploid, in
effect, every locus is sex-linked.
• Examples of Sex-Linked
Traits in Humans:
– Hemophilia
– Duchenne’s Muscular
Dystrophy
– Red-Green Color Blindness
• The above are all recessive,
exhibiting a characteristic
pattern of inheritance:
– A female can be a
heterozygous “carrier” but a
man cannot.
– Males, since they always
exhibit the trait, are much
more commonly affected by
it, though the allele occurs in
equal frequencies in females.
A Genetic Cross With Sex Linkage
• Red/white eye color in Drosophila:
• The white locus is on the sex chromosome, the
white allele is recessive, therefore:
• W = red, w= white;
• In females:
• WW, Ww, = red-eye female
• w w = white-eyed females
• In males:
• W= red-eye male
• w= white-eyed male
• One key indicator of sex-linkage is that
reciprocal crosses give different results:
• Cross (purebreeding) red-eyed females to white-
eyed males
• F1: All males and all females have red eyes
• Reciprocal cross: white females crossed to red
males
• F1: All males are white, all females red
• WHY?
• What would the F2 look like in each case?
X inactivation
• In each female cell in mammals , one X is picked at random
and inactivated.
Epistasis
• Epistasis occurs when a gene at one locus
alters the expression of a gene at another
locus.
Coat Color in Mice
• In Mice, Black coat color (allele B) is dominant to brown
coat color (allele b). Therefore, bb individuals normally
have brown coats, BB and Bb normally have black coats.
• A SECOND locus controls the way the pigment is
distributed:
• Normal distribution (C) is dominant to inhibited
distribution (c) . CC and Cc individuals therefore
normally have black coats or brown coats (depending
upon their alleles at the color locus), and cc individuals
are WHITE no matter what they have at the other locus.
This is because, if pigment is not deposited, the animal
has a white coat, regardless of the potential coat color of
the animal.
Question: A BROWN mouse is mated
to a WHITE mouse. All of the
resulting offspring are BLACK.
What is the genotype of the offspring?
What types of gametes can they
produce?
Answer:
• The parents are bbCC (brown) and BBcc
(white). We know the parents are
homozygous because ALL the offspring had
the dominant trait at each locus (if they
were heterozygous, we would see a mixture
among the offspring).
• Their offspring are BbCc (black).
• The F1 can produce four different gametes
for these two loci: BC, bC, Bc, bc.
Question:
• If these F1 mated with each other to
produce an F2, what proportion of the
offspring would be expected to be
BLACK?. What proportion would be
expected to be WHITE?
Answer.
• 9/16 black, and 4/16 white.
Pleiotropy:
• Most genes exhibit pleiotropy, they have multiple affects.
• The best examples come from genetic diseases in humans,
such as Marfan’s syndrome.
• Individuals with Marfan’s syndrome (a dominant allele,
actually a deletion that behaves as a dominant allele) have
the potential for: very tall stature, elongated fingers, curved
spine, problems with their retina, heart valve problems.
• All these effects result from an allele that affects the
distribution of the fibrillin molecule. Fibrillin fibers
surround the important areas of connective tissue in the
body, thus, alleles that modify fibrillin cause MANY
changes in the growth of the human body.
Penetrance and Expressivity
• When researchers perform genetic crosses, they take pains to
make sure their strains are all genetically uniform EXCEPT for
the alleles in question, and that the environment is identical from
one generation to the next.
– In the real world, alleles do not act alone, they act in concert with other
genes and against a variable environmental background.
– Having a particular genotype does not necessarily mean the individual will
manifest it. Also, it is possible to manifest a trait to various degrees.
• Penetrance describes the probability that, given a genotype, the
individual in question will manifest it.
– For example, Huntington’s disease is caused by a dominant
allele. 95% of persons with this allele manifest the disease,
5% do not. It has 95% penetrance.
• Expressivity is the extent to which a trait is manifest, given that it
is manifest in an individual. Many traits have variable
expressivity.
– For example, Marfan Syndrome, caused by a dominant allele,
has highly variable expressivity. Some people develop a tall
build and long fingers, others develop life-threatening
conditions.