Download Chromosomal Theory of Inheritance

Human Genetics
Chapter 15: The Chromosomal Basis of Inheritance
Genes & Chromosomes
Mendel’s “hereditary factors” were
genes, though this wasn’t known at the
time
Today we can show that genes are
located on
The location of a particular gene can be
seen by tagging isolated chromosomes
with a fluorescent dye that highlights
the gene
Chromosomal Theory of
Inheritance
 Mitosis and meiosis were first described in the late
1800s
 The chromosome theory of inheritance states:
Mendelian genes have specific
chromosomes
on
Chromosomes undergo segregation and
 The behavior of chromosomes during meiosis was said
to account for Mendel’s laws of segregation and
independent assortment
Experimental Evidence
 The first solid evidence
associating a specific gene
with a specific chromosome
came from Thomas Hunt
Morgan, an embryologist
 Morgan’s experiments with
fruit flies provided
convincing evidence that
chromosomes are the
location of Mendel’s
heritable factors
Experimental Evidence
 In one experiment, Morgan mated
male flies with white eyes (mutant)
with female flies with red eyes (wild
type or normal)
The F1 generation all had red
eyes
The F2 generation showed the
3:1 red:white eye ratio, but only
males had white eyes
 Morgan determined that the
 Morgan’s finding supported the
chromosome theory of inheritance
Sex linkage
 Sex chromosomes determine
gender of individual
XX in females, XY in males
 Each ovum contains an X
chromosome, while a sperm
may contain either an X or a Y
chromosome
 The
on
the Y chromosome codes for
the development of testes
 X chromosome has genes for
many traits NOT associated
with
Sex-linked Inheritance
 A gene located on either sex
chromosome is called a
 In humans, sex-linked usually
refers to a gene on the larger X
chromosome
 If gene is on Y chromosome

Females don’t get Y-linked
traits
Y-linked genes not common
Example: Hairy ears
X-linked Inheritance
If gene is on X
chromosome
Can inherit from
Sons always get X
chromosome from
mom and Y
chromosome from
dad
X-linked traits
Color blindness
Hemophilia
Duchene muscular dystrophy
(SCID) Severe Combined
Immunodeficiency Syndrome
AKA Bubble boy disease
X-linked recessive genes
 Sex-linked genes follow
specific patterns of
inheritance
 For a recessive sex-linked trait
to be expressed
A female needs
of the allele
A male needs only
of the allele
 Sex-linked recessive disorders
are much more common in
males than in females
Females & X-linked
 In mammalian females, one of
the two X chromosomes in each
cell is randomly inactivated
during embryonic development
 The inactive X condenses into a
 If a female is heterozygous for a
particular gene located on the X
chromosome, she will be a
mosaic for that character
Carriers
 Females can be carriers

Other X has normal dominant
gene
 Males cannot be carriers, they
either have it or they do not
Males will give gene to all
daughters, none to sons
If he has the gene all his
daughters will be carriers of
trait
Red-green color
blindness
 X-linked disorder
 Can’t differentiate these two colors
 Many people who have this are not
aware of the fact
 First described in a boy who could
not be trained to harvest only the
ripe, red apples from his father’s
orchard.
Instead, he chose green apples
as often as he chose red
 What serious consequence could
result from this?
Sex-Linked Traits:
1. Normal Color Vision:
A: 29, B: 45, C: --, D:
26
2. Red-Green ColorBlind:
A: 70, B: --, C: 5, D: -3. Red Color-blind:
A: 70, B: --, C: 5, D: 6
4. Green Color-Blind:
A: 70, B: --, C: 5, D: 2
Hemophilia
 An X-linked disorder that
causes a problem with
 If your blood didn’t have
the ability to clot and you
bruised yourself or scraped
your knee, you would be in
danger of bleeding to death
 Queen Victoria was a
carrier and she passed the
trait on to some of her
children
Hemophilia
 About 1 in every 10,000 males has hemophilia, but
only about 1 in every 1 million females inherits the
same disorder
 Why????
Males only have one X chromosome
A single recessive allele for hemophilia will
cause the disorder
Females would need two recessive alleles to inherit
hemophilia
Males inherit the allele for hemophilia on the X
chromosome from their carrier or infected mothers
Hemophilia
Hemophilia
 Hemophilia can be treated
with
and
injections of Factor VIII, the
blood-clotting enzyme that is
absent in people affected by
the condition
 Both treatments are expensive
 New methods of DNA
technology are being used to
develop a safer and cheaper
source of the clotting factor
Sex-linked Questions
 Both the mother and the father of a male hemophiliac appear
normal. From whom did the son inherit the allele for
hemophilia? What are the genotypes of the mother, the father
and the son?


 A woman is color blind. If she marries a man with normal
vision, what are the chances that her daughter will be color
blind? Will be carriers? What are her chances that her sons
will be color blind?



 Is it possible for two normal parents to have a color blind
daughter?

What is on our chromosomes?
 Each chromosome has hundreds or thousands of genes
 Genes located on the same chromosome that tend to be
inherited together are called
 Thomas Morgan found that body color and wing size of
fruit flies are usually inherited together in specific
combinations
 He noted that these genes do not assort independently,
and reasoned that they were on the same chromosome
 However, nonparental phenotypes were also produced
 Understanding this result involves exploring genetic
recombination
Genetic Recombination
 Mendel observed that combinations of traits in some
offspring differ from either parent
 Offspring with a phenotype matching one of the parental
phenotypes are called
 Offspring with nonparental phenotypes (new combinations of
traits) are called
 Morgan discovered that genes can be linked, but the linkage
was incomplete, as evident from recombinant phenotypes
Morgan proposed that some process must sometimes
break the physical connection between genes on the same
chromosome
Mechanism was the
of
homologous chromosomes
Genetic map
 Alfred Sturtevant, one of
Morgan’s students, constructed
a
, an
ordered list of the genetic loci
along a particular chromosome
 Sturtevant predicted that the
farther apart two genes are,
the higher the probability that
a crossover will occur between
them and therefore the higher
the recombination frequency
Genetic map
A
is a genetic map of a
chromosome based on recombination frequencies
 Distances between genes can be expressed as map units;
one map unit, or centimorgan, represents a 1%
recombination frequency (max value = 50%)
 Map units indicate relative distance and order, not precise
locations of genes
Human Genome Project
 The most ambitious mapping project to date has
been the sequencing of the human genome
 Officially begun as the Human Genome Project
in 1990, the sequencing was largely completed by
2003
 The project had three stages:
Genetic (or linkage) mapping
Physical mapping
DNA sequencing
Human Genome Project
A
expresses the distance
between genetic markers,
usually as the number of
base pairs along the DNA
 It is constructed by cutting
a DNA molecule into many
short fragments and
arranging them in order by
identifying overlaps
 Sequencing was then done
on the chromosomes
Gene Manipulation
 DNA sequencing has depended on
advances in technology, starting
with making recombinant DNA
 In recombinant DNA,
nucleotide sequences from two
different sources,
, are combined
in vitro into the same DNA
molecule
 Methods for making recombinant
DNA are central to
, the
direct manipulation of genes for
practical purposes
Biotechnology
 DNA technology has revolutionized biotechnology,
 One benefit of DNA technology is identification of
human genes in which mutation plays a role in genetic
diseases
 Scientists can diagnose many human genetic disorders
by using molecular biology techniques to look for the
disease-causing mutation
 Genetic disorders can also be tested for using genetic
markers that are linked to the disease-causing allele
Transgenics
 Advances in DNA technology and genetic research are
important to the development of new drugs to treat
diseases
 Transgenic animals are made by introducing genes
from
Transgenic animals are pharmaceutical “factories,”
producers of large amounts of otherwise rare
substances for medical use
“Pharm” plants are also being developed to make
human proteins for medical use
 This is useful for the production of insulin, human
growth hormones, and vaccines
Gene Therapy
 Gene therapy is the
 Gene therapy holds great potential
for treating disorders traceable to
a single defective gene
 Vectors are used for delivery of
genes into specific types of cells
(example = bone marrow)
 Gene therapy raises ethical
questions, such as whether human
germ-line cells should be treated
to correct the defect in future
generations
Causes of Genetic
Disorders
 Meiosis usually functions accurately, but problems may
arise at times
 Large-scale chromosomal alterations often lead to
or cause a
variety of developmental disorders
 In
, pairs of homologous
chromosomes do not separate normally during meiosis
May occur in Meiosis I or II
One gamete receives two of the same type of
chromosome
Another gamete receives no copy of the chromosome
Fertilization after
nondisjunction
 Nondisjunction results in gametes with an
 If the other gamete is normal, the zygote will have 2n
+ 1 (47 in humans) or 2n - 1 (45 in humans)
 Most of the time an extra chromosome prevents
development from occurring

results from the fertilization of
gametes in which nondisjunction occurred
 Offspring with this condition have an abnormal
number of a particular chromosome
Fertilization after
nondisjunction
occurs when the zygote has only
one copy of a particular chromosome (2n -1)

occurs when the zygote has three
copies of a particular chromosome (2n+1)

is a condition in which an organism has
more than two complete sets of chromosomes
Triploidy (3n) is three sets of chromosomes
Tetraploidy (4n) is four sets of chromosomes
 Polyploidy is common in plants, but not animals
 Polyploids are more normal in appearance than
aneuploids

Nondisjunction animation
Animation #2
Human Disorders due to
chromosome alterations
Alterations of chromosome number are
associated with some serious disorders
Some types of aneuploidy appear to upset
the genetic balance less than others,
resulting in individuals surviving to birth
and beyond
These surviving individuals have a set of
symptoms, or syndrome, characteristic of
the type of aneuploidy
Down Syndrome
 Down syndrome is an
aneuploid condition that
results from three copies of
chromosome 21

 Most common serious birth
defect
 1 in 700 births
 Varying degrees of mental
retardation
Due to Gart gene on 21st
chromosome
 1/2 eggs of female will carry
extra 21 and 1/2 will be normal
 Risk increases with
Incidence of Down Syndrome
Klinefelter Syndrome
Klinefelter syndrome
is the result of an extra X
chromosome in a male,
producing XXY
individuals

1 in every 2,000 births
Could be from
nondisjunction in either
parent
Turner Syndrome
 Turner syndrome
produces XO females, who
are sterile

 1 in every 5,000 births
 It is the only known viable
monosomy in humans
 Girls with Turner
Syndrome do not develop
secondary sex
characteristics such as
breast tissue and
underarm or pubic hair
Mutation types
Alterations of chromosome structure may also
lead to genetic disorders
Breakage of a chromosome can lead to four
types of changes in chromosome structure:

removes a chromosomal segment

repeats a chromosomal
segment

reverses a segment within a
chromosome

moves a segment from one
chromosome to another
Mutation types
Cri du chat
The syndrome cri du chat
(“cry of the cat”), results
from a specific deletion in
chromosome 5
A child born with this
syndrome is mentally
retarded and has a catlike
cry
Individuals usually die in
infancy or early childhood
Chronic Myelogenous
Leukemia
 Certain cancers, including chronic myelogenous
leukemia (CML), are caused by translocations of
chromosomes
 Occurs with the exchange of a large portion of
chromosome 22 with a small fragment from the tip of
chromosome 9
 Shortened, easily recognizable chromosome 22 is
called the
Genomic imprinting
 There are two normal exceptions to Mendelian genetics
 One exception involves genes located in the nucleus, and
the other exception involves genes located outside the
nucleus
Genes marked in gametes as coming from mom or dad
Genes inherited from father expressed differently than
genes inherited from mother
 For a small fraction of mammalian traits, the phenotype
depends on which parent passed along the alleles for those
traits
 Such variation in phenotype is called
 Example = Insulin-like growth factor in mice
Organelle genes
 Extranuclear genes (or
cytoplasmic genes) are
genes found in organelles
in the cytoplasm
 Mitochondria,
chloroplasts, and other
plant plastids carry small
circular DNA molecules
 Extranuclear genes are
inherited
because the zygote’s
cytoplasm comes from the
egg
Organelle genes
 The first evidence of
extranuclear genes came from
studies on the inheritance of
yellow or white patches on
leaves of an otherwise green
plant
 Some defects in mitochondrial
genes prevent cells from
making enough ATP and result
in diseases that affect the
muscular and nervous systems
For example, mitochondrial
myopathy and Leber’s
hereditary optic neuropathy
Review Questions
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13.
State the 2 basic ideas behind the chromosomal theory of
inheritance.
Explain Morgan’s experiment and how it gave evidence that genes
are located on chromosomes.
Explain sex linkage and sex-linked inheritance.
Name and describe characteristics of 4 genetic diseases that are
known to be X-linked.
Explain the idea of a “carrier” for an X-linked genetic disease.
Carry out a monohybrid cross of an X-linked trait using a Punnett
square.
Explain the idea of linked genes.
Explain the result of genetic recombination.
Identify the significance of genetic maps and linkage maps
Describe the Human Genome Project and differentiate between its 3
main stages.
Discuss the advantages of gene manipulation and biotechnology.
Describe various uses of transgenic animals.
Explain the purpose and use of gene therapy.
Review Questions
15. Define nondisjunction.
16. Differentiate between aneuploidy, monosomy, trisomy, and
polyploidy.
17. Explain the cause, frequency, and problems associated with the
following genetic syndromes: Down syndrome, Klinefelter
syndrome, & Turner syndrome.
18. Describe the effect of mutations on genes.
19. Differentiate between deletion, duplication, inversion, and
translocation mutations.
20. Explain cri du chat syndrome.
21. Explain chronic myelogenous leukemia as an example of a diseasecausing mutation.
22. Explain genomic imprinting and the effects of extranuclear genes.