Transcript PowerPoint to accompany Hole’s Human Anatomy and

Chapter 24
*Lecture Outline
with
Anatomy & Physiology
Revealed Images
*See separate Image PowerPoint slides for all
figures and tables pre-inserted into
PowerPoint without notes.
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Chapter 24
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24.1: Introduction
• Packaged into our cells are instruction manuals
• The manual is the human genome
• It is written in the language of the DNA molecules
• DNA consists of a sequence of nucleotide building blocks A, G, C, and T
• Sequences of DNA that encode particular proteins are called genes
• A gene has different forms and can vary from individual to individual
• Genetics is the study of the inheritance of characteristics
• A genome is a complete set of genetic instructions
• Genomics is the field in which the body is studied in terms of multiple,
interacting genes
• The exome consists of the protein-encoding genes of the
genome…accounts for less than 2% or the 3.2 billion DNA bases of the
human genome.
• The environment influences how genes are expressed
3
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Base pair
DNA
Gene
Cell
Nucleus
Chromosome
4
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Chromosome 7
Organs affected in cystic fibrosis
Airways
Mucus-clogged bronchi
and bronchioles.
Respiratory infections.
(Common)
DNA
Transcription
Liver
Blocked small bile ducts
impair digestion. (Rare)
mRNA
Pancreas
Blocked ducts prevent
release of digestive
enzymes, impairing fat
digestion. Diabetes
is possible. (Common)
Translation
Intestines
Hard stools may block
intestines. (Rare)
Reproductive tract
Cell
membrane
Absence of ductus deferens.
(Common)
Cystic fibrosis
transmembrane
conductance
regulator (CFTR)
protein
Skin
Salty sweat. (Common)
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(a)
(b)
24.2: Modes of Inheritance
• Genetics has the power of prediction
• Knowing how genes are distributed in meiosis and the
combinations in which they join at fertilization makes it
possible to calculate the probability that a certain trait will
appear in the offspring of two particular individuals
• These patterns in which genes are transmitted in families are
termed modes of inheritance
6
Chromosomes and Genes
Are Paired
• This normal karyotype shows 23 pairs of chromosomes:
• Pairs 1-22 are autosomes (they do not determine sex)
• Pair 23 are the sex chromosomes (XX female, XY male)
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1
2
3
6
7
8
13
14
15
19
4
9
5
11
10
16
20
17
21
Sex chromosomes
(female)
© SPL/Photo Researchers, Inc.
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18
22
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Chromosomes and Genes
Are Paired
• A gene consists of hundreds of nucleotide building blocks and exists in
variant forms called alleles that differ in DNA sequence
• An individual who has two identical alleles of a particular gene is
homozygous for that gene
• A person with two different alleles for a gene is heterozygous
• The particular combination of gene variants (alleles) in a person’s
genome constitutes the genotype
• The appearance or health condition of the individual that develops as a
result of the ways the genes are expressed is termed the phenotype
• Wild type alleles are normal and/or most common
• A mutant allele is a change from the wild type….not all cause disease
8
Dominant and Recessive
Inheritance
• For many genes, in heterozygotes, one allele determines the
phenotype
• Dominant allele masks the phenotype of the recessive allele
• Recessive allele is expressed only if in a double dose
(homozygous)
• Autosomal conditions are carried on a non-sex chromosome
• Sex-linked conditions are carried on a sex chromosome
• X-linked conditions are carried on the X chromosome
• Y-linked conditions are carried on the Y chromosome
• A pedigree is a diagram that depicts family relationships and
known genotypes and phenotypes
9
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+ = wild type
allele
cf = cystic fibrosis
allele
• Autosomal Recessive
Inheritance
• 3:1 Phenotype
• 1:2:1 Genotype
+ cf
+ cf
Carrier parents
For each child conceived:
+
+ +
25% chance
unaffected
noncarrier
(a)
cf
+
cf
cf
cf
50% chance unaffected 25% chance
carrier (cf allele inherited
affected
from either parent)
cf
I
cf
cf cf
Joe
Mary
cf cf
10
II
(b)
Punnett Square
(c)
Bill Sue Tina
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• Autosomal Dominant
Inheritance
• 1:1 Phenotype
• 1:1 Genotype
+ = wild type
allele
HD = Huntington
disease
allele
+ HD
++
Affected parent Unaffected parent
For each
Individual
conceived:
50% chance
unaffected
50% chance
affected
++
+ HD
(a)
I
HD HD
Dan
Ann
Pam
Eric
HD
11
II
(b)
Punnett Square
(c)
Different Dominance
Relationships
• Most genes exhibit complete dominance or recessiveness
• Exceptions are incomplete dominance and codominance
Plasma cholesterol (milligrams/deciliter)
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1000
Homozygotes
for FH
900
800
700
600
500
Heterozygotes
for FH
400
• Incomplete dominance
• Heterozygote has a
phenotype intermediate
between homozygous
dominant and
homozygous recessive
• Familial
hypercholesterolemia is
an example here
300
200
General
population
100
0
From Genest, Jacques, Jr., Lavoie, Marc-Andre. August 12, 1999. "Images in Clinical
Medicine." New England Journal of Medicine, pp 490. ©1999, Massachusetts Medical
Society. All Rights Reserved.
12
Different Dominance Relationships
• Codominance
• Different alleles expressed in a heterozygote are codominant
• ABO blood type is an example:
•Three alleles of ABO blood typing are IA, IB, I
•A person with type A may have the genotype IA i or IA IA
•A person with type B may have the genotype IB i or IB IB
•A person with type AB must have the genotype IA IB
•A person with type O blood must have the genotype ii
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24.1 Clinical Application
Genetic Counselors Communicate
Modes of Inheritance
14
24.3: Factors That Affect
Expression of Single Genes
• Most genotypes vary somewhat from person to person, due
to the effects of the environment and other genes
• Penetrance, expressivity, and pleiotropy describe
distinctions of genotype
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Penetrance and Expressivity
• Complete penetrance
• Everyone who inherits the disease causing alleles has
some symptoms
• Incomplete penetrance
• Some individuals do not express the phenotype even
though they inherit the alleles
• An example is polydactyly
• Variable expression
• Symptoms vary in intensity in different people
• For example, two extra digits versus three extra digits in
polydactyly
16
Pleiotropy
• Pleiotropy
• A single genetic disorder producing several symptoms
• Marfan syndrome (an autosomal dominant defect) is an
example
• People affected produce several symptoms that vary
17
Genetic Heterogeneity
• Genetic heterogeneity
• The same phenotype resulting from the actions of
different genes
• Hereditary deafness is an example
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24.4: Multifactorial Traits
• Most if not all characteristics and disorders considered “inherited” actually
reflect input from the environment as well as genes
• Polygenic traits
• Determined by more than one gene
• Examples include height, skin color, and eye color
• Blood type O without genotype ii. Due to homozygous recessive expression of
another gene, therefore blood types A and B are not possible – called Bombay
phenotype
• Multifactorial traits
• Traits molded by one or more genes plus environmental factors
• Examples include height and skin color
• Common diseases such as heart disease, diabetes mellitus, hypertension,
and cancers are multifactorial
19
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(a)
20
(b)
a: © Library of Congress; b: © Peter Morenus/University of Connecticut at Storrs
Frequency
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aabbcc
Aabbcc
aaBbcc
aabbCc
0
1
AaBbcc
AabbCc
aaBbCc
AAbbcc
aaBBcc
aabbCC
AaBbCc
aaBbCC
AAbbCc
AabbCC
AABbcc
aaBBCc
AaBBcc
aaBBCC
AAbbCC
AABBcc
AaBbCC AaBBCC
AaBBCc AABbCC
AABbCc AABBCc AABBCC
2
3
4
Number of dominant alleles
5
6
21
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AaBb
AB
Ab
aB
ab
AABB
AABb
AaBB
AaBb
AB
Number of
Phenotype dominant
frequency alleles
Ab
AABb
AAbb
AaBb
Aabb
1/16
0
4/16
1
6/16
2
4/16
3
1/16
4
Light blue
AaBb
aB
AaBB
AaBb
aaBB
aaBb
Deep blue or green
Light brown
ab
AaBb
Aabb
aaBb
aabb
Medium brown
Dark brown/black
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24.5: Matters of Sex
• Human somatic (nonsex) cells include an X and a Y
chromosome in males and two X chromosomes in females
• All eggs carry a single X chromosome
• Sperm carry either an X or Y chromosome
• Sex is determined at conception: a Y-bearing sperm
fertilizing an egg conceives a male, and an X-bearing sperm
conceives a female
23
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X
Y
X-bearing
sperm
Y-bearing
sperm
+
+
X
X
Egg
Egg
XX
female
XY
male
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Sex Determination
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• Maleness derives from a Y
chromosome gene called SRY
• The SRY gene encodes a
type of protein called a
transcription factor
• The SRY activates
transcription of genes that
direct development of male
structures in the embryo,
while suppressing formation
of female structures
SRY gene
X chromosome
Y chromosome
© Biophoto Associates/Photo Researchers, Inc.
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Genes of the Sex Chromosomes
• X chromosome
• Has over 1,500 genes
• Most genes on the X chromosome do not have
corresponding alleles on the Y chromosome
• Y chromosome
• Has only 231 protein-encoding genes
• Some genes are unique only to the Y chromosome
• The human male is hemizygous for X-linked traits because
he only has one copy of each X chromosome gene
• Some recessive X-linked traits expressed in males
include:
• Red-green colorblindness
• Hemophilia
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Hemophilia
• Passed from mother (heterozygote) to son
• Each son has a 50% chance of receiving the recessive allele from the
mother
• Each son with one recessive allele will have the disease
• Each son has no allele on the Y chromosome to mask the recessive allele
• Each daughter has a 50% chance of receiving the recessive allele from
the mother
• Each daughter with one recessive allele will be a carrier
• Each daughter with one recessive allele does not develop the disease
because she has another X chromosome with a dominant allele
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Gender Effects on Phenotype
• Sex-limited trait
• Affects a structure or function of the body that is present in
only males or only females
• Examples are beards or growth of breasts
• Sex-influenced inheritance
• An allele is dominant in one sex and recessive in the other
• Baldness is an example
• Heterozygous males are bald but heterozygous females are
not
• Genomic imprinting
• The expression of a disorder differs depending upon which
parent transmits the disease-causing gene or chromosome
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24.6: Chromosome Disorders
• Deviations from the normal chromosome number of 46
produce syndromes because of the excess or deficit of genes
• Chromosome number abnormalities may involve single
chromosomes or entire sets of chromosomes
• Euploid is a normal chromosome number
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Polyploidy
• Polyploidy
• The most drastic upset in chromosome number
• This is an entire extra set of chromosomes
• Results from formation of a diploid, rather than a normal
haploid, gamete
• Most embryos or fetuses die, but occasionally an infant
survives a few days with many abnormalities
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Aneuploidy
• Aneuploidy
• Cells missing a chromosome or having an extra
chromosome
• Results from meiotic error called nondisjunction
• Here a chromosome pair fails to separate, either at the
first or at the second meiotic division, producing a sperm
or egg that has two copies of a particular chromosome or
none, rather than the normal one copy
• When a gamete fuses with its mate at fertilization, the
resulting zygote has either 47 or 45 chromosomes, instead
of 46
• Trisomy is the condition of having an extra chromosome
• Monosomy is the condition of missing a chromosome 31
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A
A a
a
A
A a
a
Primary spermatocyte
First division
nondisjunction
A
A a
Meiosis I
a
Secondary
spermatocyte
A
a
A
a
Second
division
nondisjunction
Meiosis II
Sperm
A a
A
A a
A
a a
Fertilization of
euploid egg
Zygotes
Monosomic
(a)
Monosomic
Trisomic
Trisomic
Euploid
(b)
Euploid
Monosomic
Trisomic
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24.2 Clinical Application
Down Syndrome
34
Prenatal Tests Detect
Chromosome Abnormalities
• Several types of tests performed on pregnant women can
identify anatomical or physiological features of fetuses that
can indicate a chromosomal problem or detect the
abnormal chromosomes
35
Prenatal Tests Detect
Chromosome Abnormalities
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Chorionic
villi
Uterus
Placenta
Amniotic
membrane
Fetus
Catheter
Rare fetal cells
Cervix
Fetus
15–16
weeks
Vagina
(b) Amniocentesis
Syringe
(a) Chorionic villus sampling
(c) Fetal cell sorting
36
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37
© Bernard Bennot/SPL/Photo Researchers, Inc.
24.7: Genetics and Personalized
Medicine
• Even though it is possible for people to have their genomes
sequenced, single-gene tests or symptoms may be more useful
than knowing the sequence of the entire genome
• Gene expression is identifying which genes are active and
inactive in particular cell types, under particular conditions
• Gene expression monitors the proteins that a cell produces
• Considering patterns of gene expression my be more helpful
than knowing a sequence of DNA bases
• Changes in gene expression accompany all diseases
• Gene expression data can be used to suggest new ways to treat
diseases and to track responses to treatments
38
Important Points in Chapter 24:
Outcomes to be Assessed
24.1: Introduction
 Distinguish among gene, chromosome, and genome.
 Explain how the human genome is an economical storehouse of
information.
 Explain how the environment influences how genes are expressed.
24.2: Modes of Inheritance
 Describe a karyotype, and explain what it represents.
 Explain the basis of multiple alleles of a gene.
39
Important Points in Chapter 24:
Outcomes to be Assessed
 Distinguish between heterozygous and homozygous; genotype and
phenotype; dominant and recessive.
 Distinguish between autosomal recessive and autosomal dominant
inheritance.
24.3: Factors That Affect Expression of Single Genes
 Explain how and why the same genotype can have different
phenotypes among individuals.
24.4: Multifactorial Traits
 Describe and give examples of how genes and the environment
determine traits.
40
Important Points in Chapter 24:
Outcomes to be Assessed
24.5: Matters of Sex
 Describe how and when sex is determined.
 Explain how X-linked inheritance differs from inheritance of
autosomal traits.
 Discuss factors that affect how phenotypes may differ between the
sexes.
24.6: Chromosome Disorders
 Describe three ways that chromosomes can be abnormal.
 Explain how prenatal tests provide information about chromosomes.
41
Important Points in Chapter 24:
Outcomes to be Assessed
24.7: Genetics and Personalized Medicine
 Contrast the value of whole genome sequencing with that of single
gene tests.
 Explain how understanding gene expression patterns can improve and
personalize health care.
42
Quiz 24
Complete Quiz 24 now!
Congratulations!
You have completed
Hole’s Anatomy & Physiology, 13e.
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