Transcript Genetics - Dr Magrann

Genetics
Experimental genetics
began in an abbey garden
 The modern science of genetics
began in the 1860s when a monk
named Gregor Mandel deduced
the fundamental principles of
genetics by breeding garden
peas.
 Mendel lived and worked in an
abbey in Austria.
 Strongly influenced by his study of
physics, mathematics, and
chemistry at the University of
Vienna, his research was both
experimentally and
mathematically rigorous, and
these qualities were largely
responsible for his success.
Mendel
 In a paper published in 1866,
Mendel correctly argued that
parents pass on to their offspring
discrete hereditary factors.
 He stressed that these hereditary
factors (today called genes)
retained their individuality
generation after generation.
 In other words genes are like
marbles of different colors: just as
marbles retain their colors
permanently and do not blend, no
matter how they are mixed, genes
permanently retain their identities.
Mendel
 Mendel probably chose to study garden
peas because he was familiar with them
from his rural upbringing, they were easy
to grow, and they came in many readily
distinguishable varieties.
 Perhaps most importantly, Mendel was
able to exercise strict control over pea
plant matings.
Mendel
 The petals of the pea
flower almost
completely enclose
the reproductive
organs.
 Consequently, pea
plants usually selffertilize in nature.
That is, pollen grains
land on the egg of
the same flower.
Mendel
 Mendel could ensure
self-fertilization by
covering a flower with a
small bag so that no
pollen from another plant
could reach the egg.
 When he wanted crossfertilization (fertilization
of one plant by pollen
from a different plant), he
used a particular method
so that he could be sure
of the heritage of the new
plants.
Mendel
 Mendel worked with his
plants until he was sure
he had true breeding
varieties-- that is,
varieties for which self
fertilization produced
offspring all identical to
the parent In other words,
a “pure-bred” plant).
 For instance, he
identified a purple
flowered variety that
produced offspring plants
that all had purple
flowers.
Hybridization
 Now Mendel was ready to ask what would
happen when he crossed his different true
breeding varieties with each other.
 For example, what offspring would result if
plants with purple flowers and plants with white
flowers were cross fertilized?
 In the language of the plant and animal
breeders and geneticists, the offspring of two
different varieties are called hybrids, and the
cross-fertilization itself is referred to as
hybridization, or simply a cross.
Hybridization
 The true breeding
parental plants are called
the P generation and
their hybrid offspring are
the F1 generation.
 The offspring of F1
plants are known as the
F2 generation.
HEREDITARY PHYSICAL
CHARACTERISTICS
 Genotype and Phenotype
 Genotype means the type of genes a person
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has, or their genetic make-up.
Those genes that affect the same trait are
called alleles.
A dominant allele is given a capital letter, and a
recessive allele is given the same letter in lower
case.
For instance, having an earlobe that is
unattached to the face is a dominant trait, so we
can call it E.
An attached earlobe would then be called e.
Alleles
 Alleles occur in pairs; just as one pair of
each type of chromosome is inherited
from each parent, so too each pair of
alleles inherited from each parent.
 The allele which is traditionally
indicated by an uppercase (capital)
letter is the dominant trait.
 The allele which is traditionally
indicated by a lowercase (small) letter
is the recessive trait.
Homozygous
 If a sperm cell has e and the egg cell has e, the
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offspring must have ee.
That is called homozygous (pure) recessive.
That means the person would have an attached
earlobe.
If a sperm cell has E and the egg cell has E, the
offspring must have EE.
This is called homozygous (pure) dominant.
That means the person would have an
unattached earlobe.
Homozygous
 The term for “pure” is homo. It refers to
something being the same.
 In the old days, you had to shake up milk
because the cream would rise to the top.
Nowadays, people want less fat, so the cream
is removed before you get it; this is called
homogenized milk.
 A homogenized mixture is one that is the same
throughout, and requires no periodic mixing.
 Therefore, when the allele pairs are either EE
or ee, they are homozygous.
Heterozygous
 The opposite of homo is “hetero”, so an
allele pair that is “Ee” is heterozygous.
 If one of the sex cells has E and the
other sex cell has e, what will the
offspring have? Ee.
 What type of earlobe will they have?
Attached. Why? Because the dominant
trait is stronger, so if it is present at all, it
will manifest.
Phenotype
 The physical appearance of a person
is called the phenotype.
 A person with Ee will therefore be
called a heterozygous genotype, with
an unattached earlobe phenotype.
Sample Problems
 What earlobe alleles will a person
have who is homozygous recessive?
ee
 What earlobe alleles will a person
have who is homozygous dominant?
EE
 What earlobe alleles will a person
have who is heterozygous? Ee
Figuring the Odds
 If one of the parents is homozygous dominant
(EE), the chances of their having a child with
unattached earlobes is 100 %, because this
parent has only a dominant allele (E) to pass on
to the offspring.
 On the other hand, if both parents are
homozygous recessive (cc), there is a 100%
chance that each of their children will have
attached earlobes.
Figuring the Odds
 However, if both parents are
heterozygous, then what are the
chances that their child will have
unattached or attached earlobes?
 To solve a problem of this type, it is
customary first make a table (Punnit
Square) of the genotype of the parents
and their possible gametes.
Punnit Square
E
e
E
EE
Ee
e
Ee
ee
Figuring the Odds
 That means that when Harry meets
Sally, their child has a 25% chance (1:3)
of being ee, and 25% chance of being
EE, and 50% chance (1:1) of being Ee.
 But that’s just the genotype. What about
the phenotype (what will the child look
like)?
 There is a 75% chance (3:1) of having
an attached earlobe (ee).
Sample Test Questions
 In crossing a heterozygous parent
and a homozygous recessive parent,
what are the chances that an
offspring will receive a dominant
allele?
 Answer = 50%
Sample Test Questions
 What is the ratio for crossing two
heterozygous parents for ear lobe
attachment
 (Ee x Ee): 3:1
Sample Test Questions
 Free earlobes (E) are dominant over
attached earlobes (e).
 If two people with homozygous
attached earlobes mate, what will be
the phenotype of their offspring?
 All attached earlobes
Sample Test Questions
 What is the ratio for crossing a
heterozygous parent for ear lobe
attachment and a homozygous
recessive parent (Ee x ee):
 1:1
Sample Test Questions
 In crossing two heterozygous
parents, what are the chances for a
pure recessive offspring?
 25%
GENETIC DISORDERS
 1. Chromosome Disorders
 2. Sex Chromosomal Disorders
 3. Dominant Disorders
 4. Homozygous Recessive Disorders
 5. Incompletely Dominant Traits
 6. Sex-Linked Traits
 7. Sex-Influenced Traits
Down Syndrome
 Down syndrome is also called trisomy 21
because the person’s chromosome number 21
has three chromosomes joined together instead
of just two.
 The chances of a woman having a Down
syndrome child increase rapidly with age,
starting at about age 40.
 The frequency of Down syndrome is 1/ 800
births for mothers under 40 years of age, but
women over 40 are 10 times more likely to have
a Down syndrome child.
Down Syndrome
 Characteristics of Down
syndrome include a short
stature; an eyelid fold; stubby
fingers; a wide gap between the
first and second toes; a large,
fissured tongue; a round head; a
palm crease (the so-called
simian line), and mental
retardation, which can
sometimes be severe.
Down Syndrome
Their
personalities
are usually
cheerful,
good-natured,
and pleasant
throughout
their lives.
Amniocentesis
 Removing fluid and cells from the amniotic sac
surrounding the fetus, followed by karyotyping
can detect a Down syndrome child.
 Scientists have located genes most likely
responsible for the increased tendency toward
leukemia, cataracts, accelerated rate of aging,
and mental retardation.
 One day it might be possible to control the
expression of that gene even before birth so
that at least this symptom of Down syndrome
does not appear.
Amniocentesis
Sex Chromosomal Disorders
 All of the cells in our body have all of our chromosomes
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in the nucleus except for the egg and the sperm.
Each of these has all of our chromosomes in the nucleus,
except there is only one of the two sex chromosomes.
Since women are XX, all of her egg cells are X, but
since males are XY, a sperm can bear an X or a Y.
Therefore, the sex of the newborn child is determined
by the father.
If a Y- bearing sperm fertilizes the egg, then the XY
combination results in a male.
On the other hand, if an X-bearing sperm fertilizes the
egg, the XX combination results in a female.
Chromosomal Disorders
 All factors being equal, there is a 50%
chance of having a girl or a boy.
 If a couple has 10 children and they are
all boys, what is the chance that an
eleventh child is going to be a boy?
 Interestingly, the death rate among
males is higher than for females.
 By age 85, there are twice as many
females as males.
Jacob syndrome
 occurs in 1/ 1,000 births.
 These XYY (an extra male chromosome) males
are usually taller than average, suffer from
persistent acne, and tend to have speech and
reading problems.
 At one time, it was suggested that these men
were likely to be criminally aggressive, but it
has since been shown that the incidence of
such behavior among them may be no greater
than among XY males.
Klinefelter syndrome
 occurs in 1/ 1,500 births.
 These males with XXY (an extra female
chromosome) and they are sterile.
 They are males with some female
characteristics.
 The testes are underdeveloped, they have
some breast development, and there is no
facial hair.
 They are usually slow to learn but not mentally
retarded.
Klinefelter
syndrome
Triple-X syndrome
 occurs in 1/ 1,500 births.
 These are females with an extra female
chromosome: XXX.
 You might think they are especially feminine,
but this is not the case.
 Although in some cases there is a tendency
toward learning disabilities, most have no
physical abnormalities except that they may
have learning disabilities, menstrual
irregularities, including early onset of
menopause.
Turner syndrome
 occurs in 1/ 6,000 births.
 The individual is XO, meaning one of the sex
chromosomes is missing.
 These are females and have a short, have a
broad chest, and webbed neck.
 The ovaries and uterus are nonfunctional.
Turner females do not undergo puberty or
menstruate, and there is a lack of breast
development.
 They are usually of normal intelligence and can
lead fairly normal lives, but they are infertile
even if they receive hormone supplements.
Turner’s Syndrome
Dominant Disorders:
Neurofibromatosis
 Also known as Elephant Man disease, this is one of the
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most common genetic disorders.
It affects roughly 1/ 3,000 people.
It is seen equally in every racial and ethnic group
throughout the world.
At birth or later, the affected individual may have six or
more “coffee with milk” colored spots (known as
cafe-au-lait) on the skin.
Such spots may increase in size and number and may
get darker.
Small benign tumors (lumps) called neurofibromas may
occur under the skin or in various organs.
Neurofibromatosis
Neurofibromatosis
 In most cases, symptoms are mild, and patients
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live a normal life.
In some cases, however, the effects are severe.
Skeletal deformities, including a large head, are
seen, and eye and ear tumors can lead to
blindness and hearing loss.
Many children with neurofibromatosis have
learning disabilities and are hyperactive.
The abnormal gene is on chromosome 17.
Homozygous Recessive
Disorders: Tay - Sachs disease
 This disease usually occurs among Jewish people.
 At first, it is not apparent that a baby has Tay-Sachs
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disease.
However, development begins to slow down between
four months and eight months of age, and neurological
impairment and psychomotor difficulties then become
apparent.
The child gradually becomes blind and helpless,
develops uncontrollable seizures, and eventually
becomes paralyzed.
There is no treatment or cure for Tay-Sachs disease, and
most affected individuals die by the age of three or four.
It is caused by a genetic enzyme deficiency.
Cystic Fibrosis
 This is the most common lethal genetic
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disease among Caucasians in the United
States.
About 1 in 20 Caucasians is a carrier, and
about 1/ 2,500 births have the disorder.
In these children, the mucus in the bronchial
tubes is particularly thick and interferes with
breathing, and the lungs get infected
frequently.
New treatments have raised the average life
expectancy to 28 years of age.
The cystic fibrosis gene is located on
chromosome 7.
Phenylketonuria (PKU)
 This occurs in 1 / 5,000 births, so it is not as frequent as
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the disorders previously discussed, however, PKU is
tested for in routine blood screenings of all newborns in
the United States.
This is the disease that offspring of first cousins are
more likely to get.
PKU people lack an enzyme that is needed to break
down an amino acid (phenylalanine), and so the amino
acid accumulates in the urine.
These people have to have a special diet that does not
contain that amino acid.
If they get too much of it, they will get neurological
problems and mental retardation.
That’s why nutrition labels have to warn when they
contain phenylalanine.
Incompletely Dominant Traits
 Incomplete dominance is exhibited when
there is an intermediate phenotype.
 These people can be carriers of a
disorder without being sick themselves.
 Their children may have the disorder, or
they also may be carriers.
 When they are carriers, they are said to
have the “trait” of the disorder, but not
the disease.
Sickle-Cell Disease
 This is an incompletely dominant
disorder.
 In persons with sickle-cell disease, the
red blood cells aren’t round disks like
normal red blood cells; they are irregular.
 In fact, many are sickle shaped, like a
banana with points on both ends.
 The red blood cells do not carry oxygen
well, and they get stuck in arteries also.
Sickle-Cell Disease
Sickle-Cell Disease
 Therefore, they suffer from poor circulation,
anemia, poor resistance to infection, internal
bleeding, pain in the abdomen and joints, and
damage to internal organs.
 In malaria-infested Africa, infants with sickle-cell
disease die (they got a bad chromosome from
both parents), but infants with sickle-cell trait
(they got a bad chromosome from only one
parent) actually have better resistance to
malaria than a normal human being.
Sickle-Cell Disease
 The malaria parasite normally reproduces
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inside red blood cells.
But a red blood cell of a sickle-cell trait infant
kills the parasite.
Therefore, the only people who survive in Africa
well are those with sickle cell trait.
That’s why about 60% of the population in
malaria-infested regions of Africa has sickle cell
trait.
Unfortunately, 25% of their offspring can get the
sickle cell disease.
Malaria
Sex-Linked Traits
 Traits controlled by alleles on the sex
chromosomes are said to be sex-linked;
an allele that is only on the X
chromosome is X-linked, and an allele
that is only on the Y chromosome is Ylinked.
 Most sex-linked alleles are on the X
chromosome since it is larger.
 All of the following disorders are sexlinked.
X-Linked Disorders
 X-linked conditions can be dominant or
recessive, but most known are
recessive.
 More males than females have the
following diseases / traits.
 If a male has an X-linked condition, his
daughters are often carriers, so her male
children are also likely to have the
condition.
Male Pattern baldness
 From a gene that is
inherited from the
mother. For you
guys, if your mother’s
father was bald, you
are more likely to be
bald. It doesn’t
matter if your father
is bald or if his father
is bald. You get the
baldness gene from
your mother’s father.
X-linked Recessive Disorders
 Three well-known X-linked recessive
disorders (more common in males than
females) are color blindness, muscular
dystrophy, and hemophilia.
Color Blindness
 In the human eye, there are three
different types of cone cells (remember,
they sense color vision).
 These different types are sensitive to
either the color red, green, or blue.
 The gene for the red and green cells is
on the X chromosome.
COLOR BLINDNESS TEST
 About 8% of
Caucasian men have
red-green color
blindness.
 Opticians have special
charts by which they
detect those who are
color blind.
Muscular Dystrophy
 As you can tell by the name, this disease is characterized
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by a wasting away of the muscles.
The most common form is X-linked and occurs in about
1/ 3,600 male births.
Symptoms, such as waddling gait, toe walking, frequent
falls, and difficulty in rising, may appear as soon as the
child starts to walk.
Muscle weakness progresses to the point where they
need a wheelchair.
Death usually occurs by age 20; therefore, affected
males are rarely fathers.
The disease is from a carrier mother to carrier daughter.
Hemophilia
 About 1/10,000 males is a hemophiliac.
 It is due to the absence of a clotting factor.
 It is called the bleeder’s disease because the
blood does not clot.
 Every time they get a bruise, they have to have
either a blood transfusion or an injection of a
clotting protein, which they keep in their
refrigerator since they need it so often.
Hemophilia
 In the early 1900’s, hemophilia was prevalent
among the royal families of Europe, and all of
the affected males could trace their ancestry to
Queen Victoria of England.
 Of her 26 grandchildren, five grandsons had
hemophilia and four granddaughters were
carriers.
 Because none of Queen Victoria’s forbearers or
relatives were affected, it seems that the faulty
allele she carried arose by mutation either in
Victoria or in one of her parents.
Hemophilia
 Her carrier daughters, Alice and Beatrice,
introduced the gene into the ruling houses of
Russia and Spain, respectively.
 Alexis, the last heir to the Russian throne
before the Russian Revolution, was a
hemophiliac.
 There are no hemophiliacs in the present British
royal family because Victoria’s eldest son, King
Edward VII, did not receive the gene and
therefore could not pass it on to any of his
descendants.
Sex-Influenced Traits
 The length of the index
finger is sex-influenced.
 In females, an index finger
longer than the fourth finger
(ring finger) is dominant.
 In males, an index finger
longer than the fourth finger
seems to be recessive.
Stem Cell Research:
Discussion
Genetic Testing for Cancer
Genes: Discussion
Choosing Gender:
Discussion
Designer Children:
Discussion
Designer Children
Designer Children
Designer Children
Designer Children
Designer Children
Reproductive and
Therapeutic Cloning:
Discussion
We are half way through the
course!