Title: 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)
1Introduction to GeneticsReading Freeman,
Chapter 13 (read twice, do all the questions at
the back of the chapter), also Chapter 12 (to
review meiosis, mostly)
2Information
- 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.
3WHAT 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.
4What 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.
5Example
- 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 humansCCU 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.
6- 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
7- 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
8(No Transcript)
9- 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 during development.
10- 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
11Mitosis
- 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. - A cell gives rise to two, smaller but genetically
identical copies of itself. - It IS a duplication of the genetic complement of
a eukaryote cell. Since it is usually followed
by cell division, 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.
Do not bother to memorize the phases of
mitosis/meiosis, I do not care
12Sexual 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.
13Diploidy
- 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.
14Meiosis
- 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
materialthus, 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.
15www.biologycorner.com
The ancestral sexual species Probably had a life
cycle similar To that pictured above.
Meiosis results in 4 daughter cells Daughter
cells are haploid Daughter cells have unique
combinations of chromosomes Daughter cells do
not have homologous pairs Meiosis creates
gametes (sperm and eggs) Meiosis ensures
variability in offspring
16Errors in Meiosis
- Errors in meiosis have the potential to 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 Downs 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.
17How 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.
18- 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.
19- 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.
20The 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.
21Variation 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.
22Variation 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, or both?
Stolen from-www.environment.gov.au
23Types 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..
24Distributions 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.
25A Histogram
26Types 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.
27Normal Distribution
28A Skewed Distribution
29Bimodal Distribution
30Mean, Median, Variance, etc.
- The distribution of numerical values can be
described by several statistics - (Arithmetic) Mean the average xSx/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 - s2(S(x-x)2/N-1 )
- Standard Deviation sthe square root of the
variance.
31Dominance
- 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.
32- Example Alleles for albino coloration 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.
media.ebaumsworld.com/..
33Some 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.
34Typical manifestation of lissencephaly
Grady Stiles Junior, as a young man
35Codominance
- 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.
36Human 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.
37- Most traits are not coded by a single genethe
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-
38Phenotype vs. Genotype
- An organisms PHENOTYPE is its observable
characteristics. - An organisms 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.
39How 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.
40Genes 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.
41Geographic 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.
42In 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.
43Genetics 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.
44- 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.
45Much 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
didnt 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 Mendels success. - Mendel was among the first scientists to think in
quantitative, rather than strictly qualitative
terms.
46Mendels 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 Mendels particles, was discovered.
47A 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.
48(No Transcript)
49Questions
- 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?
50Answers
51Another 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?
52Independent 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.
53(No Transcript)
54- 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.
55Sample 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 AApigmented
- Aapigmented
- aaalbino
- Attached earlobes result from two recessive
alleles at the EARLOBE locus. - therefore EEnon-attached earlobes
- Eenon-attached earlobes
- eeattached earlobes
56- 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?
57SOLUTION
- 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 mans gametes carry a SINGLE a allele for
pigmentation, and a single E allele for earlobes. - The womans gametes carry a SINGLE A allele for
pigmentation and a single e allele for earlobes.
58- (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).
59Now, 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?
60SOLUTION
- 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
61Punnet 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.
62- 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.
63QUESTION
- 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 husbands, or her sons?
64ANSWER
- Remember, the F1 male (her son) can produce four
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 sons, but it couldnt be
her husbands.
65Testing 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
66Test 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.
67Test 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.
68The 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
69This is how we would do a Chi-Square test
- if the expected ratio is 1/41/41/41/4, 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?
70Answer
- 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
71What the _at_!?? 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 freedomN-1 where Nthe number
of comparisons - QUESTION How many degrees of freedom were there
for the cross we just did?
72- ANSWER N-13 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)
73- ANSWER With three degrees of freedom, the
probability of departure is gt.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 gt.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 (Plt.50). 5
depart to the extent that the c2 value is 7.81 or
more (Plt.05).
74Most 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 Plt.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?
75- 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.
76Linkage
- Linkage is the result of two loci being located
close together on the same chromosome. It causes
a departure from independent assortment (thus,
Mendels second law is incorrect, but he didnt
know about chromosomes). - In crosses involving two loci, linkage causes
certain combinations of alleles to be
over-represented in an individuals gametes.
77Example 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?
78Answer
- The F1 are Wild Type
- With no linkage, the expected proportion of
sepia-eyed, ebony bodied flies is 25.
79Now, imagine we got this data
- Eyes Body Number Observed
- Red Normal 123
- Sepia Normal 77
- Sepia Ebony 119
- Red Ebony 81
80Are 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??
81- 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/E17.8 - The loci are linked.
- QUESTION Why are there fewer SEPIA NORMAL and
RED EBONY?
82- Answer Linkage causes the GRANDPARENTAL
phenotypes to be over-represented in the progeny
from a test cross. - MOM DAD
- Egg
sperm - F1
- gametes (without recombination)
- gametes (with
recombination)
SE EB
se eb
SE EB
se eb
se eb
SE EB
SE EB
se eb
SE EB
se eb
EB
se
SE BE
eb
83Linkage 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 (8177)/400.40
- Hint-the recombinants are the F2 that do not
resemble the grandparents.
84- 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 10040 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.
85This 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)
86An 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.
87- 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
88- 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
89- 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.
90Sex-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.
91- 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.
92- Examples of Sex-Linked Traits in Humans
- Hemophilia
- Duchennes 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.
93A 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
94- 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?
95(No Transcript)
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97X inactivation
- In each female cell in mammals , one X is picked
at random and inactivated.
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99Epistasis
- Epistasis occurs when a gene at one locus alters
the expression of a gene at another locus.
100Coat 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.
101Question 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?
102Answer
- 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.
103Question
- 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?
104Answer.
- 9/16 black, and 4/16 white.
105Pleiotropy
- Most genes exhibit pleiotropy, they have multiple
affects. - The best examples come from genetic diseases in
humans, such as Marfans syndrome. - Individuals with Marfans 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.
106Penetrance 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, Huntingtons 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.