Transcript daughter Nicolas ii

Chapter 24
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1
24.2 Gene Linkage
• Each chromosome contains many alleles in a
definite fixed order
– Fixed because each allele has its own location on
the chromosome called locus
• Linkage group – all the alleles on one
chromosome that are inherited together
• Two trait crosses assume the alleles are on
nonhomologous chromosomes
• Alleles that are linked do not show independent
assortment
2
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Muscular dystrophy
Atherosclerosis susceptibility
Insulin-resistant diabetes mellitus
Ichthyosis
Eye color (green/blue)
Hair color (brown)
Acute myeloid leukemia
Alzheimer disease (late onset)
Deafness
Hemolytic anemia
Ovarian carcinoma
Colorectal cancer
Cardiomyopathy
3
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A
a
B
b
crossing-over
during meiosis
A
a
B
b
50%
50%
2 types of gametes in
equal proportions
a. Genes closely linked
4
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A
a
B
b
no crossing-over
during meiosis
crossing-over
during meiosis
A
a
A
a
B
b
b
B
97%
3%
recombinant gametes
4 types of gametes in unequal proportions
b. Genes further apart on chromosome
5
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A
a
B
b
crossing-over
during meiosis
a
B
b
no crossing-over
during meiosis
A
a
B
b
50%
50%
2 types of gametes in
equal proportions
a. Genes closely linked
A
crossing-over
during meiosis
A
a
A
a
B
b
b
B
97%
3%
recombinant gametes
4 types of gametes in unequal proportions
b. Genes further apart on chromosome
6
24.1 Gene Linkage
• During meiosis, crossing-over sometimes occurs
between nonsister chromatids in a tetrad.
– Chromatids exchange genetic material.
• If crossing-over occurs, a dihybrid produces four
types of gametes instead of two.
• The occurrence of crossing-over can help tell the
sequence of genes on a chromosome.
S
R
Gbetween distant genes
– Crossing-over occurs
more
often
Z
than between closer
genes.
r
g
s
z
7
24.2 Sex-Linked Inheritance
• Normally, both males and females have 23
pairs of chromosomes.
– 22 pairs are called autosomes.
– One pair is the sex chromosomes.
• Differ between sexes
• Human males are XY
• Human females are XX
– The X and Y are non-homologous and contain
different combinations of genes.
8
24.1 Sex-Linked Inheritance
• Sex-linked traits are controlled by genes on
the sex chromosomes.
– X-linked alleles are found on the X
chromosome.
• Most sex-linked traits
• No matching gene on the Y
– Y- linked ones are found on the Y chromosome.
• Very few alleles on the much smaller Y chromosome
9
24.2 Sex-Linked Inheritance
• For X-linked traits, a male receives an X-linked
allele from his mother from her X chromosome.
• The Y chromosome from the father does not
carry an allele for the trait.
• Most X-linked genetic disorders are recessive.
– Females must receive two recessive alleles.
• One from each parent
– Male only needs one recessive X from his mother.
10
Sex-Linked Alleles
• When examining X-linked traits, the allele on the X
chromosome is shown as a letter attached to the X
chromosome
– XB = normal vision
Xb = color blindness
• Example for red-green colorblindness
– Well known X-linked recessive disorder
– Carrier – female capable of passing recessive allele
– More color-blind males than color-blind females
11
Sex-Linked Alleles
Genotypes
Phenotypes
XBXB
Female who has normal color vision
XBXb
Carrier female who has normal color vision
XbXb
Female who is color blind
XBY
Male who has normal vision
XbY
Male who is color blind
12
Sex-Linked Alleles
• Sample of sex-linked cross
• Male with normal vision and a heterozygous
female
• What is the chance they will have a color-blind
daughter?
• A color blind son?
13
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XBY
Parents
♀
×
XBXb
oocytes
♀
Xb
XBXB
XBXb
sperm
XB
XB
Y
XBY
XbY
Key
XB= Normal vision
Xb= Color blind
Normal vision
Color blind
Phenotypic Ratio
Females All
Males 1
1
Offspring
Figure 24.3
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Pedigree for X-Linked Disorders
• Most sex-linked disorders are carried on the
X chromosome.
• X-linked recessive disorder
– More males than females will have the disorder.
– The recessive allele on the X chromosome is always
expressed in males.
– The Y chromosome lacks an allele for the disorder.
– Disorders are often are passed from grandfather to
grandson.
• The daughters of a male with the disorder are carriers.
15
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XbY grandfather
XBXB
XBY
XBXb daughter
XBY
XbXb
XbY
XBY
XBXB
XBXb
XbY grandson
Key
= Unaffected female
B
b
X X = Carrier female
XbXb = Color-blind female
XBY = Unaffected male
XbY = Color-blind male
XBXB
Figure 24.4
X-linked Recessive
Disorders
• More males than females are affected.
• An affected son can have parents who have the
normal phenotype .
• For a female to have the characteristic, her father
must also have it. Her mother must have it or be a
carrier.
• The characteristic often skips a generation from the
grandfather to the grandson.
• If a woman has the characteristic, all of her sons
will have it.
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Pedigree for X-linked Disorders
• X-linked dominant disorder
– Only a few are known.
– Affected males pass the trait only to daughters
who have a 100% chance of inheriting the
disorder.
– Females can pass the dominant allele to both
sons and daughters causing the disorder.
– Example disorder is incontinentia pigmenti
which causes discoloration of the skin.
17
X-linked Recessive Disorders of
Interest
• Colorblindness
– Affects about 8% of Caucasian males.
– Bright greens seen as tans and reds as reddish-brown
• Duchenne muscular dystrophy
– Characterized by a wasting away of the muscles
– Symptoms include waddling gait, toe walking, frequent
falls
– Caused by absence of protein dystrophin
18
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fibrous
tissue
abnormal muscle
normal tissue
Abnormal muscle in muscular dystrophy
(left, right): Courtesy Dr. Rabi Tawil, Director, Neuromuscular Pathology Laboratory, University of Rochester Medical Center;
(center): Courtesy Muscular Dystrophy;
Figure 24.5
19
X-linked Recessive Disorders of
Interest
• Fragile X syndrome
– Caused by an abnormal number of repeat
sequences in the genome
– Most common cause of inherited mental impairment
• Range from mild learning disabilities to more severe
intellectual disabilities
• Most common known cause of autism
– Males also have characteristic physical abnormalities
• Less frequent and milder symptoms in females
20
X-linked Recessive Disorders of
Interest
• Hemophilia
– Disease is caused by absence or minimal presence
of a clotting factor.
– Two types of hemophilia exist.
• Hemophilia A caused by a lack of clotting factor VIII
• Hemophilia B caused by a lack of clotting factor IX
– The affected individual’s blood either does not clot
or clots very slowly.
– They bleed excessively after external injury, but
also bleed internally, especially at the joints.
21
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Key
Unaffected male
Hemophiliac
Unaffected female
Carrier
Queen Victoria
Prince Albert
4 children of 9
are shown
Victoria
Frederick III
(Germany)
Alice
Louis IV
(Hesse)
Princess
Helena of
Waldeck
Leopold
(died at 31)
Beatrice
Prince Henry of
Battenberg
12 children of 26
are shown
Henry
Irene
Frederick
(died at 3)
Alexandra
Nicholas II
(Russia)
Alice
Alexander Alfonso XII
(Earl of
(Spain)
Athlone)
Victoria
Leopold
(died at 32)
6 children of 34
are shown
Waldemar
(died at 56)
Figure 24.6
Henry
(died at 4)
Alexei
(murdered)
Rupert
(died at 21)
Alfonso
(died at 31)
Gonzalo
(died at 20)
(queen): © Stapleton Collection/Corbis; (prince): © Huton Archive/Getty Images;
22
24.3 Changes in Chromosome
Number
• Humans normally receive 22 autosome
pairs and two sex chromosomes.
• Some individuals are born with either too
many or too few autosomes or sex
chromosomes.
• This is most likely due to nondisjunction in
meiosis.
23
24.3 Changes in Chromosome
Number
• Nondisjunction
– This can occur during meiosis I, when both members of
a homologous pair go into the same daughter cell/
– Or it can take place during meiosis II, when the sister
chromatids fail to separate and both daughter
chromosomes go into the same gamete.
– Results in trisomy or monosomy when fertilized
• In trisomy, a chromosome is present in three copies.
• In monosomy, a chromsome is present in one copy.
24
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pair of
homologous
chromosomes
Meiosis I
normal
normal
nondisjunction
Meiosis II
Fertilization
Zygote
2n
Figure 24.7a
2n
2n + 1
2n - 1
25
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pair of
homologous
chromosomes
Meiosis I
nondisjunction
Meiosis II
Fertilization
Zygote
2n + 1
Figure 24.7b
2n + 1
2n - 1
2n - 1
26
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
pair of
homologous
chromosomes
pair of
homologous
chromosomes
Meiosis I
nondisjunction
normal
normal
nondisjunction
Meiosis II
Fertilization
Zygote
2n
a.
Figure 24.7
2n
2n + 1
2n - 1
2n + 1
2n + 1
2n - 1
2n - 1
b.
27
24.3 Changes in Chromosome
Number
• Normal development depends on exactly two
of each kind of chromosome.
– Trisomies tolerated better than monosomies
• Only trisomy 21 (Down syndrome) has a reasonable
chance of survival after birth.
• Chromosome 21 is one of the smallest
chromosomes.
28
24.3 Changes in Chromosome
Number
• Chances of survival are greater when trisomy or
monosomy involves the sex chromosomes.
• In normal XX females, one of the X chromosomes
is inactivated and becomes a darkly stained mass
called the Barr body.
• A Barr body is an inactive X chromosome.
• Therefore, cells of females function with a single X
chromosome, like males.
29
24.3 Changes in Chromosome
Number
• Abnormal numbers of sex chromosomes
– Normal XX females have one X chromosome
inactive.
• A zygote with one X chromosome (Turner syndrome) can
survive.
– All extra X chromosomes become deactivated.
• Poly-X females and XXY males are seen fairly frequently.
– Extra Y chromosomes are also tolerated.
• Jacobs syndrome (XYY) is due to nondisjunction during
meiosis II of spermatogenesis.
30
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Down Syndrome
• Down Syndrome – trisomy 21
– Most common autosomal trisomy among humans
– Easily recognized physical features
– Chances of having a Down syndrome child
increase rapidly with age, starting at about age 40
– Some symptoms may be due to expression of Gart
gene
• Mild to severe mental impairment
– Diagnosis possible via karyotyping
32
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Figure 24.8a
© Jose Carrilo/PhotoEdit
33
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extra chromosome 21
21
Gart
gene
© CNRI/SPL/Photo Researchers, Inc.
Figure 24.8b
34
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extra chromosome 21
21
Gart
gene
a.
b.
a: © Jose Carrilo/PhotoEdit; b: © CNRI/SPL/Photo Researchers, Inc.
Figure 24.8
35
Changes in Sex Chromosome Number
• An abnormal sex chromosome number is caused by
inheriting too many or too few X or Y chromosomes.
• Nondisjunction during oogenesis or spermatogenesis
results in gametes with too few or too many X and Y
chromosomes.
• Fertilization of the gametes can lead to various syndromes.
36
Changes in Sex Chromosome Number
• A person with only one X chromosome is a
female (Turner syndrome).
• A person with more than one X chromosome
plus a Y is a male (Kleinfelter syndrome).
• Presence of Y chromosome, not the number of
X, determines maleness.
– SRY gene produces a hormone, testis-determining
factor
– Plays a key role in male genital development
37
Changes in Sex Chromosome
Number
• Turner syndrome
– Females have one X chromosome.
– Usually are short with malformed features, such as
webbed neck, high palate, and small jaw.
– Many have congenital heart and kidney defects.
– Most have ovarian failure and do not undergo
puberty or menstruate without hormone therapy.
38
Changes in Sex Chromosome
Number
• Klinefelter syndrome
– A male with 2 X and one Y chromosome
– Subtle symptoms; usually not diagnosed until age
15
– Usually experience speech and language delays
– Require assisted reproduction to father children
39
Changes in Sex Chromosome
Number
• Poly X Females or Triplo-X
– Poly-X females have more than two X
chromosomes.
– They are usually taller, with no other distinctive
phenotypes.
– Some have delayed motor and language
development.
– Some may have menstrual difficulties, but most do
so regularly and are fertile.
– Their children usually have normal karyotypes.
40
Changes in Sex Chromosome
Number
• Jacobs Syndrome
– XYY males result from nondisjunction during
spermatogenesis.
– Males are usually taller, suffer from persistent acne,
and tend to have speech and reading
abnormalities.
– There is typically no behavioral differences between
an XY and XYY male.
41
24.4 Changes in Chromosome
Structure
• Chromosomal mutations occur when chromosomes
break.
– Environmental agents – radiation, organic chemicals, or
viruses - can cause chromosomes to break.
– Usually, the break reunites to create same sequence of
genes.
• Results of failure to reunite properly
– Deletion, duplication, translocation, or inversion
– Mutations can occur during meiosis, leading to
syndromes in offspring.
42
Deletions and Duplications
• Deletion
– Occurs when a single break causes a chromosome
to lose an end piece or when two simultaneous
breaks lead to the loss of an internal chromosomal
segment.
– Inheriting one normal chromosome and one with a
deletion can result in a syndrome due to not having
a pair of alleles.
• William’s syndrome – loss of piece of chromosome 7
• Cri du chat – chromosome 5 missing an end piece
43
Deletions and Duplications
• William’s syndrome
– Children look like pixies because of turned-up
noses, wide mouths, small chins, and large ears.
– They exhibit poor academic skills, but excellent
verbal and musical skills.
• Cri du chat syndrome
– Children have a small head, are mentally impaired
and have facial abnormalities.
– Abnormal glottis and larynx cause a cry resembling
that of a cat.
44
Deletions
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a
a
b
b
+
c
deletion
c
d
d
e
e
f
f
g
g
h
lost
h
a.
b.
Courtesy The Williams Syndrome Association
Figure 24.9
45
Deletions and Duplications
• Duplication
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– Chromosomal
segment is repeated in
the same chromosome
or in a nonhomologous
chromosome.
– Individual has more
than two alleles for
certain traits.
a
a
b
b
c
c
duplication
d
d
inversion
e
e
e
f
d
g
f
g
a
b
Courtesy Kathy Wise
Figure 24.10
46
Deletions and Duplications
• Inversion
– The segment joins in a direction opposite from
normal.
• Inv dup 15 syndrome
– Inverted duplication on chromosome 15
– Causes poor muscle tone, mental impairment, seizures,
curved spine, autistic characteristics, including poor speech,
hand flapping and lack of eye contact
47
Translocation
• Translocation
– Translocation involves the exchange of chromosomal
segments between two nonhomologous chromosomes.
– A person who has both of the involved chromosomes
has the normal amount of genetic material and is
healthy.
– If the chromosome exchange breaks an allele into two
pieces, the person who inherits only one of the
translocated chromosomes will have only one copy of
certain alleles and three copies of certain other alleles.
48
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b.
b: © Fred, Herbert, and Hendrik van Dijk. “Images of Memorable Cases, 50 Years at the Bedside: Case 133.”
• One type of Down syndrome is caused by a
translocation between chromosomes 21 and 14.
• Alagille syndrome is caused by translocation
between chromosomes 2 and 20.
49
Inversion
– A segment of a
chromosome is turned 180
degrees.
– Reverse sequence of
alleles can lead to altered
gene activity.
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A
a
B
b
C
D
E
F
G
region of
inverted
segment crossing-over
e
d
c
f
g
homologous
chromosomes
Figure 24.12
C
A B
a
c
b
f
g
D
g
f
c
d
e
E
F
G
A
B
C
d
D
e
b
a
E
F
G
duplication and
deletion in both
50
Inversion
• Crossing-over between an inverted
chromosome and the non-inverted homologue
– Can lead to recombinant chromosomes that
have both duplicated and deleted segments
51
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a
a
a
a
b
b
b
c
b
c
h
+
duplication
c deletion
lost
c
d
d
e
e
e
f
f
f
g
g
g
d
d
inversion
e
e
d
f
g
h
Figure 24.9a
Figure 24.10a
Deletion
Duplication
inverted
segment
a
a
b
c
d
a
B
b
C
e
m
m
n
d
n
l
o
e
o
D
d
c
f
p
f
p
E
g
q
q
g
F
G
h
r
r
h
Figure 24.11a
Translocation
C
A
a
g
E
F
f
G
f
g
homologous
chromosomes
Figure 24.12
g
f
c
d
e
b
C
D
B
c
translocation
e
A
B
b
c
l
A
region of
crossing-over
d
e
b
a
Inversion
D
E
F
G
duplication and
deletion in both
52