Transcript You Light Up My Life

PowerLecture:
Chapter 21
Chromosomes and
Human Genetics
Learning Objectives




Describe how an understanding of
chromosomes helps to account for events
that compose mitosis and meiosis.
Name some ordinary and extraordinary
chromosomal events that can create new
phenotypes (outward appearances).
Understand how changes in chromosome
structure and number can affect the
outward appearance of organisms.
Distinguish autosomal recessive inheritance
from sex-linked recessive inheritance.
Learning Objectives (cont’d)



Explain how changes in chromosomal
number can occur and present an example
of such a change.
List examples of phenotypic defects and
describe how each can be treated.
Explain how knowing about modern
methods of genetic screening can minimize
potentially tragic events.
Impacts/Issues
Menacing Mucus
Menacing Mucus
Cystic fibrosis (CF) is a debilitating genetic
disorder.




Persons with two recessive genes
will suffer from excessive
accumulations of mucus in their
lungs.
The defective gene is located on
chromosome 7 and codes for a membrane
transport protein called CFTR.
Many thousands of prospective parents
have been screened for CF; genetic testing,
however, is not without controversy.
Useful References for Impacts/Issues
The latest references for topics covered in this section can be found at
the book companion website. Log in to the book’s e-resources page at
www.thomsonedu.com to access InfoTrac articles.
 Cystic
Fibrosis Foundation
 Cystic Fibrosis Foundation: Gene Therapy
and CF
 InfoTrac: Constant Battle: Kerri Marks Is One
of the Survivors, Living Under a Disease’s
Invisible Clock. Jennifer Becknell. Herald,
July 10, 2006.
How Would You Vote?
To conduct an instant in-class survey using a classroom response
system, access “JoinIn Clicker Content” from the PowerLecture main
menu.
 Do
we as a society want to encourage
women to give birth only to offspring who will
not develop serious gene-based medical
problems?


a. Yes, in order to prevent needless suffering and
expense.
b. No, the diversity represented by special-needs
children is important to a society.
Useful References for
How Would You Vote?
The latest references for topics covered in this section can be found at
the book companion website. Log in to the book’s e-resources page at
www.thomsonedu.com to access InfoTrac articles.

InfoTrac: Ohio Court Limits Relief for Fetal Testing
Error; Compensation Denied for Costs of Raising
Disabled Child. Judy Greenwald. Business
Insurance, Mar. 13, 2006.
 InfoTrac: In New Tests for Fetal Defects, Agonizing
Choices for Parents. Amy Harmon. The New York
Times, June 20, 2004.
 InfoTrac: Offer All Pregnant Women Fetal Genetic
Testing. Sherry Boschert. OB GYN News, Dec. 15,
1999.
Section 1
Genes and
Chromosomes
Genes and Chromosomes
Understanding inheritance starts with genechromosome connections.




Genes, the units of instruction for heritable
traits, are segments of DNA arranged along
chromosomes in linear order; each gene thus
has its own locus.
Diploid cells have pairs of homologous
chromosomes that are very much alike;
homologues interact and segregate during
meiosis.
Alleles are different forms of a gene; they often
arise by mutation.
Genes and Chromosomes


Independent assortment dictates that genes
generally move into gametes independently of
one another.
Crossing over leads to genetic recombination
during meiosis.
Genes and Chromosomes
Closely linked genes tend to stay together
when gametes form.



When the distance between two genes on the
same chromosome is very short, the genes are
said to show linkage (they are “linked”); close
genes generally travel together and are not
segregated independently.
Genes that are far apart on a chromosome will
segregate independently as a result of crossing
over between them.
Closely
linked
genes in
parents:
B
a
A
A
AB
b
x
a
b
B
ab
meiosis, gametes form
Genes stay together
in gametes.
A
B
50% AB
a
b
50% ab
Fig. 21.1a, p. 388
A
Weaker
linkage in
parents:
C
AC
a
x
c
A
a
ac
c
C
meiosis, gamete formation
Genes less
likely to stay
together as
gametes
form.
a
A
C
c
Most gametes
have parent’s
genotype.
a
A
c
C
A few
gametes have
recombinant
genotypes.
Fig. 21.1b, p.388
Closely
linked
genes in
parents:
B
a
A
b
x
a
A
AB
b
B
ab
meiosis, gametes form
Genes stay together
in gametes.
A
B
50% AB
a
b
50% ab
Stepped Art
Fig. 21.1a, p. 388
A
Weaker
linkage in
parents:
x
C
AC
a
c
A
a
ac
c
C
meiosis, gamete formation
Genes less
likely to stay
together as
gametes
form.
a
A
C
c
Most gametes
have parent’s
genotype.
a
A
c
C
A few
gametes have
recombinant
genotypes.
Stepped Art
Fig. 21.1b, p.388
Genes and Chromosomes
The X and Y chromosomes are quite
different genetically.



Sex chromosomes determine gender; males
have one X and one Y chromosome while
females have two X chromosomes.
The X and Y chromosomes can synapse in a
small region along their length, allowing them to
behave as homologues during meiosis.
Useful References for Section 1
The latest references for topics covered in this section can be found at
the book companion website. Log in to the book’s e-resources page at
www.thomsonedu.com to access InfoTrac articles.
 Rocklin
and Roseville Today: Genetic
Behaviors Go Beyond X and Y
Chromosomes
 InfoTrac: Cord-Blood Storage Is Big
Business, But Is It Worth It? Blythe Bernhard.
Orange County Register (Santa Ana, CA),
June 2, 2006.
Section 2
Picturing Chromosomes
with Karyotypes
Picturing Chromosomes with Karyotypes

A karyotype is a “picture” of a person’s
chromosomes captured when the
chromosomes have condensed to their
metaphase (mitosis) state.
Figure 21.2f
Picturing Chromosomes with Karyotypes


Cells are harvested from a patient, grown in
the lab, and arrested in metaphase of mitosis
(using colchicines) before the cells are
disrupted and the chromosomes recovered.
Once photographed, the chromosomes are
arranged in their homologous pairs and
analyzed.
a. Add cells from
a small blood
sample
b. Centrifugation
d. Put cells on
microscope
© 2007 Thomson Higher Education
c. Prepare
cells
e. Photograph
cell
Fig. 21.2(1), p.389
Animation: Karyotype Preparation
CLICK
TO PLAY
Useful References for Section 2
The latest references for topics covered in this section can be found at
the book companion website. Log in to the book’s e-resources page at
www.thomsonedu.com to access InfoTrac articles.
 InfoTrac:
Microarray Analysis of Cell-Free
Fetal DNA in Amniotic Fluid: A Prenatal
Molecular Karyotype. Paige B. Larrabee et al.
American Journal of Human Genetics, Sept.
2004.
Section 3
How Sex Is Determined
How Sex Is Determined
Sex is a question of X or Y.


Gender of the human offspring is determined by
the father’s sperm.
•
•
If an X-bearing
sperm fertilizes an
egg, the offspring
will be female.
If a Y-bearing
sperm fertilizes an
egg, the offspring
will be male.
Figure 21.3a
female
(XX)
male
(XY)
eggs
sperm
diploid germ
cells in female
meiosis, gamete
formation in
both female and
male
sex chromosome
combinations
possible in new
individual
X
x
Y
X
x
X
X
X
X
XX
XX
Y
XY
XY
Fig. 21.3a, p.390
Animation: Human Sex Determination
CLICK
TO PLAY
How Sex Is Determined
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

The Y chromosome has a “male-determining
gene” (SRY) that codes for proteins that cause
testes to form; in the absence of SRY, a female
forms automatically.
Nonsexual traits are also coded for on the sex
chromosomes, mostly on the X.
Genes that are specific to the X and Y
chromosomes are called X-linked genes and
Y-linked genes, respectively.
Figure 21.3b
appearance of
“uncommitted” duct
system of embryo
at 7 weeks
Y chromosome
present
Y chromosome
absent
testis
ovary
ovary
penis
uterus
vagina
testis
Fig. 21.3b, p.390
appearance of
“uncommitted” duct
system of embryo
at 7 weeks
Y chromosome
present
Y chromosome
absent
testis
ovary
ovary
penis
uterus
vagina
testis
Stepped Art
Fig. 21.3b, p.390
Animation: Effects of the SRY Gene
CLICK
TO PLAY
How Sex Is Determined
In females, one X is inactivated.


Most or all of the genes on one of the X
chromosomes are switched off in early
development, a process called X inactivation;
which X becomes inactivated (maternal or
paternal) is random.
•
•
The inactivated X chromosome becomes condensed
into a Barr body.
The female body is a mosaic of cells in which one or
the other of the original pair of X chromosomes
inherited from her parents is active.
How Sex Is Determined

Anhidrotic ectodermal dysplasia is a
condition in females in which the active X
chromosome in certain tissues carries a
mutated gene that blocks the formation of
sweat glands in patches of tissue over the
surface of the body.
Fig. 21.4a, p.391
Useful References for Section 3
The latest references for topics covered in this section can be found at
the book companion website. Log in to the book’s e-resources page at
www.thomsonedu.com to access InfoTrac articles.
 InfoTrac:
The Genetic Legacy of the Mongols.
Tatiana Zerjal et al. American Journal of
Human Genetics, Mar. 2003.
Section 4
Human Genetic Analysis
Human Genetic Analysis
A pedigree
shows genetic
connections.


The analysis of
family pedigree
charts provides
data on
inheritance
patterns through
several
generations.
Figure 21.5
Animation: Pedigree Diagrams
CLICK
TO PLAY
Human Genetic Analysis

A person who is heterozygous for a recessive
trait (carrier) may show the dominant
phenotype but is still capable of passing the
recessive gene on.
•
•
•
The term genetic abnormality is applied to a
genetic condition that is a deviation from the usual,
or average, but is not life threatening.
A genetic disorder is more appropriately used to
describe conditions that cause medical problems.
Syndrome refers to a set of symptoms that
characterize a disorder by appearing together.
Human Genetic Analysis
Genetic analysis may predict disorders.


Genetic analysis, beginning with determination
of the parental genotypes, is the first step to
identifying any risks a couple may have in
producing a child with a genetic disorder.
Figure 21.6
Human Genetic Analysis

Not all factors leading to disorders can be
readily quantified; it is important for prospective
parents to recognize that each pregnancy will
hold the same risks.
Useful References for Section 4
The latest references for topics covered in this section can be found at
the book companion website. Log in to the book’s e-resources page at
www.thomsonedu.com to access InfoTrac articles.
 GeneTests: Amish
Lethal Microcephaly
 InfoTrac: LCT Announces Results for
Treating Huntington’s Disease. AsiaPulse
News, Aug. 2, 2005.
Section 5
Inheritance of Genes
on Autosomes
Inheritance of Genes on Autosomes
Inherited recessive traits cause a variety of
disorders.


Recessive inheritance is characterized by the
following:
•
•
•
Either parent can carry the recessive allele on an
autosome.
Heterozygotes are symptom free; homozygotes are
affected.
Two heterozygous parents have a 50% chance of
producing heterozygous children and a 25% chance
of a homozygous recessive child. When both parents
are homozygous, all children will be affected.
Inheritance of Genes on Autosomes

Examples of autosomal recessive inheritance
include:
•
•
•
Cystic fibrosis.
Phenylketonuria (PKU), resulting from the abnormal
buildup of phenylalanine due to the lack of an
enzyme that normally
breaks it down.
Tay-Sachs disease,
which affects primarily
infants, is characterized
by lack of an enzyme to
break down lipids in the
brain.
Figure 21.7
Animation: Autosomal
Recessive Inheritance
CLICK
TO PLAY
Inheritance of Genes on Autosomes
Some disorders are due to dominant genes.


Inheritance of dominant alleles demonstrates
the characteristics below:
•
•
•
Because such alleles are usually expressed (even in
heterozygotes), the trait appears in each generation.
If one parent is heterozygous and the other
homozygous recessive, there is a 50% chance that
any one child will be heterozygous.
Dominant alleles, even if they cause severe genetic
disorders, persist in the population due to mutation,
nonreproductive effects, or post-reproductive onset.
Inheritance of Genes on Autosomes

Examples of autosomal
dominant inheritance
include:
•
Marfan syndrome results
from a defective form of
fibrillin, found in connective
tissue; one effect is to
disrupt both structure and
function of smooth muscle
cells of the aorta.
Figures 21.8 and 21.9
Inheritance of Genes on Autosomes
•
•
•
Achondroplasia (dwarfism)
results in heights of about 4
feet, but has no other serious
effects; homozygotes, though,
usually are stillborn.
Familial hypercholesterolemia
results in elevated levels of cholesterol due to few
cell receptors for low-density lipoproteins.
Huntington disease, a serious degenerative
disease of the nervous system with an onset from
age 30 onward; homozygotes always die, thus adults
are always heterozygous.
Figure 21.10
Animation: Autosomal
Dominant Inheritance
CLICK
TO PLAY
Animation: Marfan Syndrome
CLICK
TO PLAY
Useful References for Section 5
The latest references for topics covered in this section can be found at
the book companion website. Log in to the book’s e-resources page at
www.thomsonedu.com to access InfoTrac articles.
 InfoTrac:
Geographic Distribution of Disease
Mutations in the Ashkenazi Jewish
Population Supports Genetic Drift over
Selection. Neil Risch et al. American Journal
of Human Genetics, April 2003.
Section 6
Inheritance of Genes on
the X Chromosome
Inheritance of Genes on
the X Chromosome
X-linked recessive inheritance.


X-linked recessive inheritance is demonstrated
by the following:
•
•
The mutated gene occurs only on the X
chromosome.
Heterozygous females are phenotypically normal
because a dominant gene on the other X
chromosome masks the recessive’s effects; a male
will be affected if he inherits a recessive gene on his
sole X chromosome.
Inheritance of Genes on
the X Chromosome
•
A normal male mated with a female heterozygote
together have a 50% chance of producing carrier
daughters and a 50% chance of producing affected
sons. In the case of a homozygous female and a
normal male, all daughters will be carriers and all
sons affected.
Figure 21.11
Animation: X-Linked Inheritance
CLICK
TO PLAY
Inheritance of Genes on
the X Chromosome

Examples of X-linked recessive inheritance
include:
•
•
Duchenne muscular dystrophy is a condition in
which the protein dystrophin is missing, causing
muscle fibers to weaken.
Red/green color blindness is an inconvenience but
is not life threatening.
Inheritance of Genes on
the X Chromosome
•
Hemophilia A, where the inability of the blood to clot
because the genes do not code for the necessary
clotting agent (factor VIII) can lead to death from any
cut or internal bleeding.
Figure 21.12
Inheritance of Genes on
the X Chromosome

Some types of X-linked abnormalities are quite
rare.


Faulty enamel trait is one of very few
known examples of a trait caused by a
dominant mutant allele that is X-linked;
it is expressed in heterozygous females
but is less pronounced than in males.
Testicular feminizing syndrome (androgen
insensitivity) is an abnormality of an XY individual in
which a mutation in the X chromosome results in
defective receptors for the male sex hormones;
individuals have external female features, but no uterus
or ovaries.
Figure 21.13
Inheritance of Genes on
the X Chromosome
Many factors complicate genetic analysis.



Before diagnosing a case, geneticists often
must pool many pedigrees and make detailed
analyses of clinical data to keep track of
instances where multiple mutations can lead to
the same phenotype.
As an example, some conditions can occur
because of changes to autosomes or to the X
chromosome.
Useful References for Section 6
The latest references for topics covered in this section can be found at
the book companion website. Log in to the book’s e-resources page at
www.thomsonedu.com to access InfoTrac articles.
 InfoTrac:
Significant Improvement in
Spirometry after Stem Cell Transplantation in
One Duchenne Muscular Dystrophy Patient.
Zhiping Li et al. Chest, Oct. 2005.
Section 7
Sex-Influenced
Inheritance
Sex-Influenced Inheritance
Sex-influenced traits either appear more
frequently in one sex than the other or the
phenotype differs depending on whether the
person is male or female.



Genes for such traits appear on the autosomes.
Appearance of the trait may be due to the
influence of sex hormones on gene expression.
Sex-Influenced Inheritance

A male will develop
pattern baldness if
he is homozygous or
heterozygous for a
particular gene, but a
female will develop
the condition only if
she is homozygous
and then only late in
life.
Figure 21.14
Useful References for Section 7
The latest references for topics covered in this section can be found at
the book companion website. Log in to the book’s e-resources page at
www.thomsonedu.com to access InfoTrac articles.
 InfoTrac:
Genetic Variation in the Human
Androgen Receptor Gene Is the Major
Determinant of Common Early-Onset
Androgenetic Alopecia. Axel M. Hillmer et al.
American Journal of Human Genetics, July
2005.
Section 8
Changes in a
Chromosome or Its
Genes
Changes in a Chromosome or Its Genes


A gene mutation is a change to one or
more of the nucleotides that composite a
given gene.
Various changes in a chromosome’s
structure may cause a genetic disorder.
Changes in a Chromosome or Its Genes

A deletion is the loss of part of a chromosome
due to breaks caused by viruses, chemicals, or
irradiation.
•
•

Loss of a portion of chromosome
5, for example, causes the
disorder cri-du-chat.
Normal genes on the
homologue can
compensate for deleted
genes.
Duplication occurs when a gene sequence is
repeated thousands of times.
Figure 21.15
Animation: Deletion
CLICK
TO PLAY
Animation: Duplication
CLICK
TO PLAY
Changes in a Chromosome or Its Genes

A translocation occurs when a part of one
chromosome is transferred to a
nonhomologous chromosome.
•
It is seen in some forms of cancer, such as when
a segment of chromosome 8 is translocated to
chromosome 14.
Animation: Translocation
CLICK
TO PLAY
Changes in a Chromosome or Its Genes
•
A chronic type of leukemia is caused by an
abnormally long chromosome 9 (Philadelphia
chromosome), which is due to a piece of
chromosome 22 that has become attached.
Figure 21.17
Useful References for Section 8
The latest references for topics covered in this section can be found at
the book companion website. Log in to the book’s e-resources page at
www.thomsonedu.com to access InfoTrac articles.
 Five
P Minus Society: Family Support Group
for Children with Cri du Chat Syndrome
 BBC: Translocation
 InfoTrac: Brazilian Researchers Connect
Gene Mutation to Blood Conditions. Xinhua
News Agency, June 20, 2006.
Section 9
Changes in
Chromosome Number
Changes in Chromosome Number
Several kinds of events can change the
number of chromosomes in gametes.



Aneuploidy is a condition in which the cells of
an affected individual end up with one extra or
one less chromosome than is the normal
number.
Polyploidy is a condition in which new
individuals have three or more of each
chromosome; it is lethal in humans.
Changes in Chromosome Number
Nondisjunction is a common cause of
abnormal numbers of autosomes.


Nondisjunction during mitosis or meiosis
results in a change in chromosome number.
•
•
If a gamete with an extra chromosome (n + 1) joins a
normal gamete at fertilization, the diploid cell will be
2n + 1; this condition is called trisomy.
If an abnormal gamete is missing a chromosome, the
zygote will be 2n – 1: monosomy.
Animation: Nondisjunction
CLICK
TO PLAY
n+1
n+1
n-1
n-1
chromosome
alignments at
metaphase I
nondisjunction
at anaphase I
alignments at
metaphase II
anaphase II chromosome
number in
gametes
Fig. 21.18, p.400
n+1
n+1
n-1
n-1
chromosome
alignments at
metaphase I
nondisjunction
at anaphase I
alignments at
metaphase II
anaphase II chromosome
number in
gametes
Stepped Art
Fig. 21.18, p.400
Changes in Chromosome Number

Down syndrome results from trisomy 21.
•
•
Trisomy 21 occurs in 1 out
of 1,000 live newborns in
North America; children will
show some form of mental
retardation, and 40% have
heart defects.
There is an increased
probability that a woman
over age 35 will conceive an
embryo with Down syndrome, yet 80% of trisomic
infants are born to younger mothers simply because
women ages 18-35 have more babies.
Figure 21.19
Changes in Chromosome Number
Nondisjunction also can change the number
of sex chromosomes.


Turner syndrome involves females
whose cells have only one X
chromosome (designated XO).
•
•
Turner’s individuals are sterile and have
other phenotypic problems such as
premature aging and shorter life
expectancy.
Approximately 1 in 1,000 females are XXX; two of
the Xs are condensed into Barr bodies, allowing
normal development.
Figure 21.20
Changes in Chromosome Number

In Klinefelter syndrome, nondisjunction
results in an extra X chromosome in the cells
(XXY) of affected males.
•

This occurs in about 1 out
of 500 live-born males and
results in mild mental
retardation and low fertility.
XYY condition: XYY males
result from nondisjunction
of duplicated Y chromosomes during meiosis.
•
Affected individuals are taller than average with
normal phenotype.
Figure 21.20
Victims of Neurobiological Disorders
 John
Nash; Virginia Woolf
Figure 21.21
Useful References for Section 9
The latest references for topics covered in this section can be found at
the book companion website. Log in to the book’s e-resources page at
www.thomsonedu.com to access InfoTrac articles.
 InfoTrac: A Very
Special Wedding. Claudia
Wallis. Time, July 24, 2006.
 InfoTrac: Common Age Misconception about
Down Syndrome. PR Newswire, May 2,
2006.