Transcript Genetics

• A few facts about
inheritance known since
ancient times:
– children resemble their
– Domestication followed by
selective breeding to
improve plants and
animals. Mostly 10-12,000
years ago.
– Some lines are truebreeding, others have a
variety of offspring types.
Different breeds can be
produced through selective
Some Older, Incorrect Theories
Hippocrates, an ancient Greek, taught the
idea of pangenesis, that inheritance comes
from the presence in each organ of tiny
replica organs. These replicas moved
through the blood to the semen, where they
formed a tiny human which grew in its
mother’s womb. Problem: if you cut off
someone’s arm, their children still have
Preformation is the idea that each sperm
contains a miniature person: development is
merely a process of enlarging and maturing
the person already present in the sperm cell.
There is another version of this theory that
puts the miniature person in the egg instead
of the sperm.
Inheritance of acquired characteristics. The
idea that events that occur in your life affect
your offspring directly. For instance,
constant stretching of the giraffe’s neck
made its offspring’s neck longer. Often
associated with Lamarck, but the idea is
much older.
More Ancient Ideas
Relative contribution of male and
female. Many cultures believed that
the child grew from the semen, with
the female’s role merely to act as a
source of nutrition, like planting a seed
in the garden. Also, allegedly some
New Guinea cultures didn’t know that
sex was necessary for reproduction,
which implies the female was the sole
source of the child.
Blending inheritance. Like mixing red
paint with white paint: the results is
pink paint, and there is no way to ever
separate out the red and white.
Plants and sex. Although it was known
to many ancient cultures, the idea that
all plants have male and female parts
wasn’t widely accepted until the early
Gregor Mendel lived in what is now the Czech
Republic (then part of the Austria-Hungarian
Empire) from 1822 to 1884
After high school he became a monk. The
monastery sent him to the University of Vienna.
After college he did plant hybridization
experiments in the monastery garden, growing
more than 28,000 pea plants between 1856 and
Wrote up the work as “Experiments on Plant
Hybridization” in a local scientific journal, where it
was promptly forgotten. In those days, Darwin’s
work was stirring controversy. Darwin had an
incorrect notion of genetics: evolution was
reconciled with genetics in the 1930’s, in the
“modern synthesis”.
Mendel was elected abbot and gave up his
studies, dying in 1884.
In 1900, 3 scientists working on plant breeding
independently found his paper, read it, and
understood how it explained their own work: the
“rediscovery” of Mendel. This is the start of
modern genetics.
Mendel’s Basic Innovations
Inheritance is particulate: genes are
not blended together, even if the
effects of the genes get blended. For
instance, in some plants if you cross a
red flower with a white flower, the
offspring have pink flowers. But, if you
then cross 2 of the pink flowers
together, the next generation has
some red flowers and some white
flowers, unchanged by having been in
a pink parent.
Counting offspring, and seeing
experimental numbers as imperfect
reflections of underlying simple ratios.
As an example, if you flipped a coin
1000 times you might get 477 heads
and 523 tails. This represents a 1:1
ratio that contains a small amount of
random error.
Mendel’s Experiments
He worked with pea plants. Peas
have male and female parts all
within one flower. You can take
the pollen (male gamete,
equivalent to sperm) and put it on
the pistils (female structures) of
another plant, where it fertilizes
the ovule (female gamete) to form
a zygote, the first cell of the next
Peas can self-pollinate (or “self”):
the male pollen can fertilize the
female ovule within a single plant.
This is the closest possible
genetic relationship.
He worked with true-breeding
lines: all peas within the line
looked similar.
He started with 7 different truebreeding lines, which differed for 7
distinct characters.
Examining One Trait
Start with flower colors: one line has
purple flowers, another line has white
flowers. These two lines are called the
“P generation”, for parental. When
crossed, their offspring are the F1
generation. All of the F1 offspring are
purple. Purple is called the dominant
trait, because it is expressed in the F1
offspring. White is recessive, not
expressed in the F1 offspring.
When the F1 plants are self-pollinated
(or crossed with each other), their
offspring are the F2 generation. The
F2 are the grandchildren of the P
generation. The F2 were found in a
ratio of ¾ purple to ¼ white.
The same effects were seen for all 7
traits: if two lines are crossed together,
the F1 all look like one of the parents,
and the F2 are ¾ like one parent (the
dominant trait) and ¼ like the other
parent (the recessive trait).
Explanation and Vocabulary
Genes are the factors that control the inherited traits. Genes are made of DNA; they
are part of the chromosomes.
Individual versions of a gene are called alleles. Here, the flower color gene has two
alleles: a purple allele and a white allele.
Pea plants (and humans and most higher organisms) are diploid: they have 2 copies
of each gene, one from each parent. The gametes (sperm and egg, or pollen and
ovule) are haploid: only 1 copy of each gene.
When the sperm fertilizes the egg, the two haploid genomes mix, forming a new
diploid, which is the zygote, the first cell of the offspring.
The true breeding purple line produces only pollen carrying the purple allele, and all
the ovules from the true-breeding white line have the white allele. The true breeding
lines are homozygotes: the two copies of the flower color gene in each plant are
identical. True breeding is the same as homozygous.
So, when pollen from a purple flower fertilizes ovules from a white flower, the F1
offspring gets one purple allele and one white allele. It is a heterozygote: the two
copies of the gene are different. “Hybrid” is the same as heterozygous.
In the heterozygote, the dominant allele is expressed and the recessive allele is not
expressed. The heterozygote looks just like the dominant homozygote. The
genotype of the plants-- their genetic constitutions-- are different (one is a
homozygote and one is a heterozygote), but their phenotype--their physical
appearance– is the same: purple flowers.
More Explanation
More Explanation
P is the symbol we will use for the
purple allele.
p is the symbol for the white allele.
Both alleles are different versions of
the flower color gene.
Since peas have 2 copies of each
gene (diploid), a pea plant can be PP,
Pp, or pp.
The parental plants, from true
breeding lines, are homozygous: PP
(purple) and pp (white).
PP parents can only make P gametes,
and pp parents can only make p
The P pollen fertilizes the p ovule,
producing the diploid Pp F1 offspring.
The Pp plants are purple, because P is
dominant and p is recessive.
The homozygous PP plants and the
heterozygous Pp plants are both
purple: they have different genotypes
(genetic constitutions) but the same
phenotype (physical appearance).
Still More Explanation
The F1 heterozygotes are Pp. Half of the
gametes they make are P and the other half
are p.
When the F1 plants are self-pollinated, both
the male and the female parts make P and p
Fertilization is random, so there are 4
1. P pollen fertilizes a P ovum, giving PP
2. P pollen fertilizes a p ovum, giving Pp
3. p pollen fertilizes a P ovum, giving Pp
4. p pollen fertilizes a p ovum, giving pp
Adding these up, ¼ of the offspring are PP,
½ are Pp, and ¼ are pp.
Phenotypes: PP and Pp are purple, so ¾
purple. Pp is white, so ¼ white.
The Punnett square is a simple way of
combining gametes and seeing the
genotypes of the next generation.
Cross Summary
• Mendel’s Law of Segregation: Diploids produce equal
numbers of gametes from each allele. The gametes
combine at random to produce the next generation.
Back Cross
So far we have seen what happens when two
homozygotes are crossed (all the offspring are
heterozygotes), and what happens when two
heterozygotes are crossed (genotype ratio of ¼
PP, ½ Pp, ¼ pp; phenotype ratio of ¾ purple to ¼
One other possibility: crossing a heterozygote to a
homozygote. This is called a backcross: an F1
heterozygote is crossed to one of the parental
A backcross can be made to the dominant
parental type or to the recessive parental type. A
testcross is the latter type: crossing a
heterozygote to a homozygous recessive parental
In a backcross, the heterozygote (Pp) produces ½
P gametes and ½ p gametes. The homozygote
produces only one kind of gamete, P or p.
When the gametes combine, ½ are homozygotes
and ½ are heterozygotes.
If the backcross is to the dominant parent, all
offspring show the dominant phenotype.
If the backcross is to the recessive parent (a
testcross), ½ the offspring have the dominant
phenotype and ½ have the recessive phenotype.
Complications: Variations in
All of Mendel’s traits had two alleles, a
dominant allele (expressed in the
heterozygote) and a recessive allele
(not expressed in the heterozygote).
This all-or-nothing expression is now
called “complete” dominance
Another form is “incomplete”
dominance, where the phenotype of
the heterozygote is intermediate
between the two parental
homozygotes. The classic case is red
flowers x white flowers giving pink
How incomplete dominance works:
each red flower color allele makes red
pigment. The white alleles don’t make
pigment. So, the red homozygotes
make twice as much pigment as the
heterozygotes. We perceive the
difference in the amount of pigment as
red vs. pink.
In co-dominance, the heterozygote expresses both
parental types. A good example is the ABO blood
There are 4 blood types: A, B, AB, and O. Red
blood cells of type A have a glycolipid (a
carbohydrate attached to a lipid in the membrane)
on their cell membranes. B cells have a different
glycolipid. AB cells have both glycolipids, and O
cells have neither.
The glycolipids are made by genes with the symbol
I. The IA allele makes A glycolipids, and the IB
allele makes the B glycolipids. People with AB
blood have a heterozygous genotype: IA IB. They
express both types of glycolipids on their red blood
cells. This is what “co-dominant” means.
O blood comes from the third allele, called i
because it is recessive. Homozygotes (ii) don’t
make either A or B glycolipids. An IA i
heterozygote had A blood, and a IB i heterozygote
makes B blood.
This is an example of multiple alleles (3 alleles in
this case: IA, IB, and i). Most genes have more than
2 alleles.
Single Genes Can Have Multiple
• Sickle cell anemia—
caused by a change
in hemoglobin gene.
Gives rise to many
symptoms: skull
deformation, heart
failure, joint and
muscle pain, spleen
enlargement. Also—
resistance to
Lethal Genes
In another variation on dominance,
some alleles are lethal when
homozygous—they kill the organism
before birth.
Two examples: achondroplastic
dwarves and Manx cats.
The heterozygote shows the unusual
When two heterozygotes mate, their
sperm and eggs combine randomly,
producing ¼ DD, ½ Dd, and ¼ dd
zygotes. BUT: the DD zygotes all die.
This leaves only the Dd (dwarf) and dd
(normal) types, in a ratio of 2:1, or 2/3
dwarf and 1/3 normal.
Thus, dwarves and Manx cats don’t
breed true: they always produce 1/3 of
the “wrong” type of offspring.
More on Lethal Genes
Environmental Effects
Most inherited traits are affected by
environmental conditions.
For instance, the hydrangea has white,
pink, and purple versions. There are
only 2 alleles: white and pigmented.
The pink and purple come from
growing the plants in different acidity
Some effects are more direct. Manx
cats have no tails due to a mutant
allele. But, cats can also have no tail
because it has been cut off—an
environmental condition.
Genetic traits are also affected by
‘background” genetics—other genes
present. Former Chicago Cubs relief
pitcher Antonio Alfonseca has a
condition called polydactyly, having
extra fingers and toes. He has 6 on
each hand and foot. More commonly
people with this condition have just a
single extra digit with no bone in it, but
the range is quite large
Two Genes Affecting One Trait
• Most traits are due to the
interaction of several
• New phenotypes can
arise from the interactions
between genes. Also,
unusual ratios of
Continuous Variation
Many traits don’t seem to fall into
discrete categories: height, for
example. Tall parents usually
have tall children. Short parents
have short children, and tall x
short often gives intermediate
height. In all cases, wide
variations occur.
Simple interactions between
several genes can give rise to
continuous variation. Also:
variations caused by environment,
and our inability to distinguish fine
distinctions lead us to see
continuous variation where there
actually are discrete classes.
Independent Assortment
Much of Mendel’s work involved pairs of
genes: how do they affect each other when
forming the gametes and combining the
gametes to form the next generation?
Simple answer: in most cases pairs of genes
act completely independently of each other.
Each gamete gets 1 copy of each gene,
chosen randomly.
Two genes:
1. seed shape. Dominant allele S is
smooth; recessive allele s is wrinkled.
2. seed color. Dominant allele Y is yellow;
recessive allele y is green.
Heterozygous for both has genotype Ss Yy,
which is smooth and yellow. Gametes are
formed by taking 1 copy of each gene
randomly, giving ¼ SY, ¼ Sy, ¼ sY, and ¼
These gametes can be put into a Punnett
square to show the types of offspring that
arise. Comes out to 9/16 smooth yellow,
3/16 smooth green, 3/16 wrinkled yellow,
and 1/16 wrinkled green.
• Most pairs of genes assort
• However, if two genes are
close together on the same
chromosome, they are said to
be linked, which means the
genes don’t do into the
gametes independently of
each other.
• The closer two genes are, the
more the parental combination
of alleles stays together. This
relationship can be used to
make maps of genes on
Some Common Genetics Diseases
Tay-Sachs disease is a neural degenerative disease
caused by the lack of the enzyme hexose aminidase
A, which normally breaks down certain membrane
lipids in the lysosomes, especially in the nerve cells
of the brain. Without the enzyme, these lipids
accumulate in the cells, poisoning them. The child is
apparently normal at birth, but starting between 6
months and two years, the child has seizures and a
loss of all skills such as crawling, sitting and feeding.
100% lethal in early childhood. No cure or treatment
Tay-Sachs is a recessive genetic disease: the victim
must inherit a defective copy of the gene from both
parents. The parents are heterozygotes (carriers)
who have no symptoms. There is a 1 in 4 risk of
another Tay-Sachs child in a family where one was
There is a reliable blood test that can detect
heterozygotes. High risk parents can take the test to
determine their risk level. Tay-Sachs is especially
prevalent among Ashkenazi (Eastern European )
Jews. In American Jewish population, about 1
person in 27 is a carrier. The French-Canadians
from the St. Lawrence River area, and their cousins,
the Louisiana Cajuns, also have a high risk of TaySachs.
Sickle-cell Disease
Sickle-cell disease is caused by a defective
hemoglobin molecule in the blood. The defect puts
a hydrophobic amino acids on the outer surface of
the protein instead of a hydrophilic amino acid. This
causes the hemoglobin molecules to crystallize into
long rods when the oxygen level in the blood gets
low. These hemoglobin rods distort the red blood
cells so they clog up the blood-carrying capillaries.
The result is muscle pain, anemia, heart
enlargement, kidney and spleen damage, and
various other problems. Various medical treatments
are used to ease the symptoms.
Sickle cell disease is recessive: homozygotes are
quite sick. Heterozygotes are normal (sometimes
called sickle cell trait), although they do have a
higher rate of sudden death while exercising, due to
sickling of the red blood cells under extreme
Sickle cell disease is common in West Africa, areas
around the Mediterranean Sea, and in India, where
malaria is found. Being a heterozygote confers a
strong resistance to malaria, which has helped
maintain this mutation in the human population.
Other hemoglobin defects, such as hemoglobin C
and thalassemia, confer malaria resistance and are
found in the same populations. The malaria
parasites live inside the red blood cells. The rods of
hemoglobin that form when the cells sickle puncture
and kill the parasites.
About 6% US African-Americans carry the HbS
Malaria vs. Sickle Cell Disease
Cystic Fibrosis
Cystic fibrosis is primarily a disease of the
lungs. The thin mucus that normally lines
the lungs is replaced by heavy, thick mucus
that traps bacteria and leads to lung
infections. Other symptoms include salty
skin and pancreas problems. In the US
today, people with cystic fibrosis have an
average life span of 33 years.
Cystic fibrosis is caused by a defective
chloride ion channel, a protein that lets Clions in and out of the cell. When chloride
leaves the cell, sodium ions follow it, and
water molecules follow the sodium. In cystic
fibrosis, the chloride ions don’t get out of the
mucus-secreting cells, so not enough water
is secreted to properly tin the mucus.
Treatment: attempts to remove the mucus
through percussion on the back, mucusthinning sprays, and antibiotics to treat
Found primarily in Northern European
populations: about 4% of US EuropeanAmerican populations are heterozygotes (no
symptoms). There are DNA-based tests for
this, but not 100% reliable.
Phenylketonuria (PKU) is a disorder of
the metabolism: the cells are unable to
break down phenylalanine, which is an
amino acid found in all proteins. The
result is that phenylalanine levels in
the blood build up to 30 times the
normal level. This poisons the
developing brain, leading to severe
mental retardation.
PKU is a recessive condition: the
parents are usually heterozygotes who
have no symptoms. About 5% of the
US population (all ethnic groups) is
heterozygous for PKU.
There is a very simple blood test for
PKU, which is given to all infants born
in the US. The disease is easily
treated by giving the children a lowphenylalanine diet until their brains
mature. Infants in most states are also
tested for several other easily detected
and treated metabolic diseases.
Some Dominant Traits
Huntington’s Disease is a neural
degenerative disease that doesn’t
appear until the victim is 40 years old
or more. It starts with clumsiness and
involuntary twitching, progresses
through paranoia and psychosis, and
ends in paralysis and death. The folk
singer Woody Guthrie had this
Dominant genetic diseases appear in
heterozygotes. Homozygotes are rare
because heterozygotes only rarely find
and mate with each other.
Huntington’s shows complete
dominance: the rare homozygotes
have the same disease as the
There is a genetic test: if it is positive,
you will get the disease. Most people
don’t take the test.
Marfan Syndrome
Marfan syndrome is a disease of the
connective tissue: the skeleton and
cardiovascular system in particular.
Symptoms include curvature of the
spine, long fingers, tall stature,
dislocated eye lens, and weakness of
the aorta. People with Marfan’s
sometimes die suddenly due to the
rupture of their aorta. Abraham
Lincoln might have had this disease.
Also Osama bin-Laden.
The disease is caused by an abnormal
fibrillin gene. Fibrillin is one of the
proteins that makes tissues elastic.
Marfan’s is a dominant trait, meaning
that the heterozygotes have the
disease. People homozygous for
Marfan’s show a more extreme version
and don’t live past infancy. Just as in
Huntington Disease, people with
Marfan’s have a 50% chance of
passing the disease to their offspring.
Retinoblastoma is a hereditary form of
cancer. Like most hereditary cancers,
it strikes young children, almost all
before age 5. Tumors grow in the
eyes, from the retinal precursor cells,
the retinoblasts. It is quite treatable if
caught early, using cryotherapy to
freeze the tumors, or radiation and
chemotherapy if necessary.
About 40% of the cases are hereditary,
inherited from a parent who had the
disease. The other 60% are
spontaneous: due to newly arising
mutations. The hereditary cases
usually affect both eyes, while the
spontaneous cases are confined to
one eye. It is inherited as a dominant
trait, so 50% of an affected person’s
children will get the disease.
Homozygotes die as early embryos
and are never born alive.
Schizophrenia: a Complex Genetic
A mental disease: thought
disorders (inability to think
logically), delusions (person is
being spied on or persecuted,
thoughts are being overheard by
others), hallucinations (voices
inside the head). Also lack of
emotional engagement, odd
walking gait, social withdrawal.
NOT multiple personalities of
“split” personality.
Onset at any time, but generally
age 16-25. Males and females
equally affected.
Treatable with anti-psychotic
drugs. But: the person must keep
taking the drugs even after feeling
More Schizophrenia
Degree of risk for schizophrenia is strongly affected by relatives who have the
1% risk for the general population
13% risk if you have 1 schizophrenic parent
35% risk if you have 2 schizophrenic parents
Monozygotic (identical) twins: 50% risk
13% of adopted children with a schizophrenic biological parent and normal
adoptive parents develop the disease.
This “runs in the family” phenomenon strongly implies genetic factors are involved.
Other factors are also involved: brain damage, viruses, family environment, life
experiences, diet, plus others. Any or all of these.
Mapping: large family studies examine markers on the chromosomes to find locations
associated with schizophrenia. That is, chromosomal locations where the alleles in a
schizophrenic parent are also found in the schizophrenic child. Potential genes on
chromosomes 22, 13, and 8.
But: the genes have been difficult to confirm. They seem to affect some families but
not others. Maybe multiple causes of the disease?