Chromosomal basis for inheritance

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Chapter 15

• Chromosomal basis for inheritance

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Mendel Genetics

• Mendel published his work in 1866
• 1900 his work was rediscovered.
• Parallels between Mendels factors chromosome
  behavior

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Mendels Genetics

• 1902 Walter Sutton
• Chromosomal theory of inheritance
• Genes are located on chromosomes
• Located at specific loci (positions)
• Behavior of chromosomes during meiosis account
  for inheritance patterns

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Fig. 15-2
P Generation
Yellow-round seeds (YYRR)
Green-wrinkled seeds ( yyrr)
y
Y
r
?
R
R
r
Y
y
Meiosis
Fertilization
r
y
R
Y
Gametes
All F1 plants produce yellow-round seeds (YyRr)
F1 Generation
R
R
y
y
r
r
Y
Y
LAW OF INDEPENDENT ASSORTMENT Alleles of genes on
nonhomologous chromosomes assort independently
during gamete formation.
LAW OF SEGREGATION The two alleles for each
gene separate during gamete formation.
Meiosis
R
r
r
R
Metaphase I
Y
y
y
Y
1
1
R
R
r
r
Anaphase I
Y
Y
y
y
Metaphase II
r
r
R
R
2
2
y
Y
y
Y
y
Y
Y
y
y
Y
y
Y
Gametes
r
R
r
r
r
R
R
R
1/4
1/4
1/4
1/4
yR
yr
Yr
YR
F2 Generation
An F1 ? F1 cross-fertilization
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3
9
3
3
1
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Fruit fly

• Thomas Morgan studied fruit flies
• Drosophila melanogaster
• Proved chromosomal theory correct
• Studied eye color
• Red is dominant, white is recessive
• Crossed a homozygous dominant female with a
  homozygous recessive male

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Wild type (w)
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Mutant (w)
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Fruit fly

• F1 offspring were all red eyed
• F2 classic 31 ratio redwhite phenotypes
• Showed the alleles segregate
• Supported the Chromosomal theory
• BUT only males were white eyed
• All females were red eyed or wild type

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Fig. 15-4
EXPERIMENT
P
?
Generation
F1
All offspring had red eyes
Generation
RESULTS
F2
Generation
CONCLUSION

P
w
w
X
X
?
Generation
X
Y

w
w
Sperm
Eggs


F1
w
w

Generation
w
w

Sperm
w
Eggs


w
w

F2
w
Generation

w
w
w
w

w
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Fruit fly

• Eye color gene is on the X-chromosomes
• Sex-linked genes
• Genes found on the sex chromosomes
• X-chromosome has more genes than Y-chromosome
• Most sex-linked genes are on the X-chromosome

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Human chromosomes

• 23 pairs
• 22 autosomes
• 1 sex chromosome pair
• XX female
• All eggs are X
• XY male
• Sperm are either X or Y
• Chromosomes are divided into 7 groups
• Based on size, shape and appearance

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Males

• Y chromosome is very condensed
• 78 genes
• Male characteristics
• Sperm production fertility

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Males

• SRY is a gene on the Y chromosome
• Sex determining region of Y
• Present gonads develop into testes
• Determines development of male secondary sex
  characteristics
• Not present then the individual develops ovaries

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Females

• X chromosome has 1000 genes
• One of the 2 X chromosomes is inactivated
• Soon after embryonic development
• Choice is random from cell to cell
• Female is heterozygous for a trait
• Some cells will have one allele and some cell
  have the other

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Females

• Barr body
• Condensed inactive X chromosome
• Stains dark

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Fig. 15-8
X chromosomes
Allele for orange fur
Early embryo
Allele for black fur
Cell division and X chromosome inactivation
Two cell populations in adult cat
Active X
Inactive X
Active X
Black fur
Orange fur
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Sex-linked

• Mom passes gene on the X-chromosome to the son
• Males have one X-chromosome
• Recessive gene is expressed
• Recessive alleles on the X are present
• No counter alleles on the Y

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Sex-linked disorders

• Mom passes sex-linked to sons daughters
• Dad passes only to daughters

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Sex-linked disorders

• Sex-linked genetic defects
• Hemophilia
• 1/10,000 Caucasian males

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Sex-linked disorders

• Colored blindness
• Red-green blindness
• Mostly males
• Heterozygous females can have some defects

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Sex-linked disorders

• Duchenne muscular dystrophy
• Almost all cases are male
• Child born healthy
• Muscles become weakened
• Break down of the myelin sheath in nerve
  stimulating muscles
• Wheelchair by 12 years old
• Death by 20

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Independent assortment
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Independent assortment

• Dihybrid testcross
• 50 phenotypes similar to parents
• Parental types
• 50 phenotypes not similar to parents
• Recombinant types
• Indicates unlinked genes
• Mendels independent assortment

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Linked genes

• Do not assort independently
• Genes are inherited together
• Genes located on the same chromosome
• Differs from Mendels law of independent
  assortment

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Linked genes

• Test cross fruit flies
• Wild-type (dihybrid)
• Gray bodies and long wings
• Mutants (homozygous)
• Black bodies and short wings (vestigial)
• Results not consistent with genes being on
  separate chromosomes

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Fig. 15-10
Testcross parents
Gray body, normal wings (F1 dihybrid)
Black body, vestigial wings (double mutant)
b vg
b vg
b vg
b vg
Replication of chromo- somes
Replication of chromo- somes
b vg
b vg
b vg
b vg
b vg
b vg
b vg
b vg
Meiosis I
b vg
Meiosis I and II
b vg
b vg
b vg
Meiosis II
Recombinant chromosomes
b vg
b vg
b vg
b vg
Eggs
Testcross offspring
965 Wild type (gray-normal)
944 Black- vestigial
206 Gray- vestigial
185 Black- normal
b vg
b vg
b vg
b vg
b vg
b vg
b vg
b vg
b vg
Sperm
Parental-type offspring
Recombinant offspring
391 recombinants
Recombination frequency

? 100 17
2,300 total offspring
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Linked genes

• More parental phenotypes
• Than if on separate chromosomes
• Greater than 50
• Gray body normal wings or black body vestigial
• Non-parental phenotype 17
• Gray-vestigial or black-normal wings
• Indicating crossing over

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• Genetic recombination
• New combination of genes
• 2 genes that are farther apart tend to cross over
  more
• 2 genes on the same chromosome can show
  independent assortment
• Due to regularly crossing over

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Genetic map

• Ordered list of gene loci
• Linkage map
• Genetic map based on recombination frequencies
• Distance between genes in terms of frequency of
  crossing over
• Higher percentage of crossing over the further
  apart the genes are
• Centimorgan (Thomas Hunt Morgan)
• A map unit

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Fig. 15-12
Mutant phenotypes
Short aristae
Cinnabar eyes
Vestigial wings
Brown eyes
Black body
0
48.5
57.5
67.0
104.5
Red eyes
Normal wings
Red eyes
Gray body
Long aristae (appendages on head)
Wild-type phenotypes
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Human genetic map

• Genetic distance is still proportional to the
  recombination frequency
• Use pedigrees
• Newer technology

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Alterations in chromosomes

• Chromosome number
• Chromosome structure
• Serious human disorders

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Alterations in numbers

• Nondisjunction
• Failure of the homologues or sister chromatids to
  separate properly
• Aneuploidy
• Gain or a loss of chromosomes due to
  nondisjunction
• Abnormal number of chromosomes
• Occurs about 5 of the time with humans

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Nondisjunction
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Fig. 15-13-3
Meiosis I
Nondisjunction
Meiosis II
Nondisjunction
Gametes
n 1
n 1
n 1
n
n
n 1
n 1
n 1
Number of chromosomes
(b) Nondisjunction of sister chromatids in
meiosis II
(a) Nondisjunction of homologous chromosomes
in meiosis I
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Monosomics

• Lost a copy of a chromosome (not a sex
  chromosome)
• Usually do not survive
• Trisomes gained a copy of a chromosome
• Many do not survive either
• 35 rate of aneuploidy (spontaneous abortions)

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Polyploidy

• More than 2 sets of chromosomes
• 3n or 4n
• Plants

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Fig. 15-14
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Alterations in Structure

• 1. Deletion
• Missing a section of chromosome
• 2. Duplication
• Extra section of chromosome
• Attaches to sister or non-sister chromatids

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Alterations in Structure

• 3. Inversion
• Reverse orientation of section of chromosome
• 4. Translocation
• Chromosome fragment joins a nonhomologous
  chromosome

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Fig. 15-15
A B C D E F G H
A B C E F G H
Deletion
(a)
A B C D E F G H
A B C B C D E F G H
Duplication
(b)
A B C D E F G H
A D C B E F G H
Inversion
(c)
A B C D E F G H
M N O C D E F G H
(d)
Reciprocal translocation
M N O P Q R
A B P Q R
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Human disorders

• Trisomes
• Babies with extra chromosomes can survive
• Chromosome 13, 15, 18, 21 and 22
• These are the smallest chromosomes

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Trisomy 13
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Trisomy 18
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Down syndrome

• Trisomy 21
• 1866 J. Langdon Down
• 1 in 750 births
• Similar distribution in all racial groups
• Similar distribution in chimps and other primates

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Down Syndrome

• Mental retardation
• Heart disease
• Intestinal problems/surgery
• Hearing problems/hearing loss
• Unstable joints
• Leukemia
• Single crease in the palm

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Down syndrome

• 20 years or younger 1 in 1700
• 20-30 years 1 in 1400
• 30-35 years 1 in 750
• 45 1 in 16

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Nondisjunction

• Higher incidence in womans eggs than in the
  mens sperm
• Womans eggs are in prophase I (meiosis) when she
  is born
• Her eggs are as old as she is!!!
• Men produce new sperm daily

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Down Syndrome

• Primarily from the nondisjunction of the
  chromosome in the womans eggs.
• Therefore the age of the mother is very important

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Sex chromosomes

• X chromosomes fail to separate properly
• Some eggs with 2 X chromosomes and some eggs with
  no X chromosome
• Produce
• XXX
• Appears normal

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Sex chromosomes

• XXY Klinefelter syndrome (1 in 500 male births)
• Is a male with some female features
• Sterile
• Maybe slightly slower than normal
• OY does not survive, need the X chromosome

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Sex chromosomes

• XO, Turner syndrome
• Female that has short statue, web neck
• Sterile
• 1 in 5000 births

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Sex Chromosomes

• XYY
• 1 in 1000 births
• Normal fertile males
• May be taller than normal

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Translocation

• Philadelphia chromosome
• Reciprocal exchange of chromosome
• 22 and 9 exchange portions
• Shortened translocated 22
• CML

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Fig. 15-17
Reciprocal translocation
Normal chromosome 9
Translocated chromosome 9
Translocated chromosome 22 (Philadelphia
chromosome)
Normal chromosome 22
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Deletion

• Cri du chat
• Cry of the cat
• Deletion of chromosome 5
• Mental retardation
• Small head
• Die in infancy

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Genomic imprinting

• Variation in phenotype
• Depends on allele is inherited from male or
  female
• Usually autosomes
• Silencing of one allele in gamete formation

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Fig. 15-18
Normal Igf2 allele is expressed
Paternal chromosome
Maternal chromosome
Normal Igf2 allele is not expressed
Wild-type mouse (normal size)
(a) Homozygote
Mutant Igf2 allele inherited from mother
Mutant Igf2 allele inherited from father
Normal size mouse (wild type)
Dwarf mouse (mutant)
Normal Igf2 allele is expressed
Mutant Igf2 allele is expressed
Mutant Igf2 allele is not expressed
Normal Igf2 allele is not expressed
(b) Heterozygotes
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Organelle genes

• Extracellular genes
• Cytoplasmic genes