Download - Mendelian inheritance - College biology
1
The Chromosomal
Basis of
Inheritance
Beyond Mendelian Ideas• Mendel’s “hereditary factors” were genes,
though this wasn’t known at the time
• Now we know that genes are located on
chromosomes at specific loci
• The location of a particular gene can be seen
by tagging isolated chromosomes with a
fluorescent dye that highlights the gene
Mendelian inheritance
• The chromosome theory of inheritance states:
– Mendelian genes have specific loci (positions) on chromosomes
– Chromosomes undergo segregation and independent assortment
• The behavior of chromosomes during meiosis is said to account for Mendel’s laws of segregation and independent assortment
P Generation Yellow-round
seeds (YYRR)
Y
F1 Generation
Y
R R
R Y
r
r
r
y
y
y
Meiosis
Fertilization
Gametes
Green-wrinkled
seeds (yyrr)
All F1 plants produce
yellow-round seeds (YyRr)
R R
YY
r ry y
Meiosis
R R
Y Y
r r
y y
Metaphase I
Y Y
R Rrr
y y
Anaphase I
r r
y Y
Metaphase IIR
Y
R
y
yyy
RR
YY
rrrr
yYY
R R
yRYryrYR1/4
1/41/4 1/4
F2 Generation
Gametes
An F1 F1 cross-fertilization
9 : 3 : 3 : 1
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.
1
2
33
2
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Morgan’s Experiments• 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
• Several characteristics make fruit flies a convenient
organism for genetic studies:
– They breed at a high rate
– A generation can be bred every two weeks
– They have only four pairs of chromosomes
• Morgan noted wild type, or normal, phenotypes that were
common in the fly populations
• Traits alternative to the wild type are called mutant
phenotypes
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Behavior: Alleles vs. Chromosome Pairs
• In one experiment, Morgan mated male flies with white eyes (mutant) with female flies with red eyes (wild type)
– 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 white-eyed mutant allele must be located on the X chromosome
• Morgan’s finding supported the chromosome theory of inheritance
PGeneration
Generation
Generation
Generation
Generation
Generation
F1
F2
All offspring
had red eyes
Sperm
EggsF1
F2
P
Sperm
Eggs
XX
XY
CONCLUSION
EXPERIMENT
RESULTS
w
w
w
w
w
w
w w
+
+
++ +
w
ww w
w
w
w
ww
+
+
+
+ +
+
Morgan mated
white eyed male
(mutant) with red
eyed female
(wild type)
Result all F1 had red eyes
An F2 cross produced a 3:1 red:white eye ratio, but only males had white eyes
Morgan determined the white-eyed mutant allele is located on the X chromosome
Morgan’s finding supported the chromosome theory of inheritance
Sex-linked genes
• In humans and some other animals, there is a
chromosomal basis of sex determination
• Humans – XY
• The SRY gene on the Y chromosome codes for the
development of testes
• Females – XX
• males are XY
• Each ovum contains an X
• Sperm contains either an X or a Y (a) The X-Y system
44 +XY
44 +XX
Parents
44 +XY
44 +XX
22 +X
22 +X
22 +Yor
or
Sperm Egg
+
Zygotes (offspring)
Sex Chromosomes - Humans
(b) The X-0 system
22 +XX
22 +X
Sex Chromosomes - Grasshoppers
(c) The Z-W system
76 +ZW
76 +ZZ
Sex Chromosomes - Birds
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(d) The haplo-diploid system
32(Diploid)
16(Haploid)
Sex Chromosomes – Bees Inheritance of Sex-Linked Genes
• A gene located on either sex chromosome is a sex-linked
gene
• Sex-linked genes follow specific patterns of inheritance, for
a recessive sex-linked trait to be expressed
– A female needs two copies of the allele
– A male needs only one copy of the allele (he only gets
one X chromosome)
• Sex-linked recessive disorders are much more common in
males than in females because they are found on the X
chromosome
(a) (b) (c)
XNXN XnY XNXn XNY XNXn XnY
YXnSpermYXNSpermYXnSperm
XNXnEggs XN
XN XNXn
XNY
XNY
Eggs XN
Xn
XNXN
XnXN
XNY
XnY
Eggs XN
Xn
XNXn
XnXn
XNY
XnY
Transmission of an X-linked recessive
disorder
X linked disorders: Color blindness, Duchenne muscular
dystrophy and Hemophilia
X Inactivation in Female Mammals
• In mammalian females, one of the two X chromosomes
in each cell is randomly inactivated during embryonic
development
• The inactive X condenses into a Barr body
• If a female is heterozygous for a particular gene located
on the X chromosome, she will be a mosaic for that
character
X chromosomes
Early embryo:
Allele for
orange fur
Allele for
black fur
Cell division and
X chromosomeinactivationTwo cell
populationsin adult cat:
Active X
Active XInactive X
Black fur Orange fur
• Linked genes tend to be inherited together because
they are located near each other on the same
chromosome
• Genes located on the same chromosome that tend to
be inherited together are called linked genes
• Morgan did other experiments with fruit flies to see how
linkage affects inheritance of two characters
• Morgan crossed flies that differed in traits of body color
and wing size
Linked Genes
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b+ vg+
Parents in testcross
Most offspring
b+ vg+
b vg
b vg
b vg
b vg
b vg
b vg
or
EXPERIMENTP Generation (homozygous)
Wild type
(gray body,normal wings)
Double mutant
(black body,vestigial wings)
b b vg vgb+ b+ vg+ vg+
EXPERIMENTP Generation (homozygous)
Wild type
(gray body,normal wings)
Double mutant
(black body,vestigial wings)
b b vg vg
b b vg vg
Double mutantTESTCROSS
b+ b+ vg+ vg+
F1 dihybrid
(wild type)
b+ b vg+ vg
EXPERIMENTP Generation (homozygous)
Wild type
(gray body,normal wings)
Double mutant
(black body,vestigial wings)
b b vg vg
b b vg vg
Double mutantTESTCROSS
b+ b+ vg+ vg+
F1 dihybrid
(wild type)
b+ b vg+ vg
Testcrossoffspring
Eggs b+ vg+ b vg b+ vg b vg+
Black-
normalGray-
vestigialBlack-
vestigialWild type
(gray-normal)
b vg
Sperm
b+ b vg+ vg b b vg vg b+ b vg vg b b vg+ vg
EXPERIMENTP Generation (homozygous)
RESULTS
Wild type
(gray body,normal wings)
Double mutant
(black body,vestigial wings)
b b vg vg
b b vg vg
Double mutantTESTCROSS
b+ b+ vg+ vg+
F1 dihybrid
(wild type)
b+ b vg+ vg
Testcrossoffspring
Eggs b+ vg+ b vg b+ vg b vg+
Black-
normalGray-
vestigialBlack-
vestigialWild type
(gray-normal)
b vg
Sperm
b+ b vg+ vg b b vg vg b+ b vg vg b b vg+ vg
PREDICTED RATIOS
If genes are located on different chromosomes:
If genes are located on the same chromosome and
parental alleles are always inherited together:
1
1
1
1
1 1
0 0
965 944 206 185
:
:
:
:
:
:
:
:
:
• Morgan found that body color and wing size are usually
inherited together in specific combinations (parental
phenotypes)
• He noted that these genes do not assort independently,
and reasoned that they were on the same chromosome
• However, non-parental phenotypes (recombinant types)
were also produced
• Understanding this result involves exploring genetic
recombination - the production of offspring with
combinations of traits differing from either parent. (We did
this in Meiosis!)
• The genetic findings of Mendel and Morgan relate to the
chromosomal basis of recombination
Genetic Recombination and Linkage
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YyRr
Gametes from green-
wrinkled homozygousrecessive parent (yyrr)
Gametes from yellow-round
heterozygous parent (YyRr)
Parental-
typeoffspring
Recombinant
offspring
yr
yyrr Yyrr yyRr
YR yr Yr yR
Recombination of Unlinked Genes:
Independent Assortment of Chromosomes
Combinations of traits in some offspring
differ from either parent
Phenotype matching one of the parental
phenotypes are parental types
Non-parental phenotypes (new
combinations of traits) are recombinant
types, or recombinants
A 50% frequency of recombination is
observed for any two genes on different
chromosomes
Recombination of Linked Genes: Crossing Over
• 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
• That mechanism was the crossing over of homologous
chromosomes
Testcross
parents
Replication
of chromo-somes
Gray body, normal wings
(F1 dihybrid)
Black body, vestigial wings
(double mutant)
Replication
of chromo-somes
b+ vg+
b+ vg+
b+ vg+
b vg
b vg
b vg
b vg
b vg
b vg
b vg
b vg
b vg
b+ vg+
b+ vg
b vg+
b vg
Recombinantchromosomes
Meiosis I and II
Meiosis I
Meiosis II
b vg+b+ vgb vgb+ vg+
Eggs
Testcrossoffspring
965Wild type
(gray-normal)
944Black-
vestigial
206Gray-
vestigial
185Black-normal
b+ vg+
b vg b vg
b vg b+ vg
b vg b vg
b vg+
Sperm
b vg
Parental-type offspring Recombinant offspring
Recombinationfrequency
=391 recombinants
2,300 total offspring 100 = 17%
Big Idea Here!
The further
apart genes
are on a
chromosome
the less likely
that that will
be transferred
together in a
cross over
event. Genes
located very
close to one
another close
to the end of
the same
choromosome
or chromotid
are often
transferred
together by
default of their
position.
Testcross
parents
Replication
of chromo-somes
Gray body, normal wings(F1 dihybrid)
Black body, vestigial wings(double mutant)
Replication
of chromo-somes
b+ vg+
b+ vg+
b+ vg+
b vg
b vg
b vg
b vg
b vg
b vg
b vg
b vg
b vg
b+ vg+
b+ vg
b vg+
b vg
Recombinantchromosomes
Meiosis I and II
Meiosis I
Meiosis II
Eggs Sperm
b+ vg+ b vg b+ vg b vgb vg+
Parental types
Testcrossoffspring
965Wild type
(gray-normal)
944Black-
vestigial
206Gray-
vestigial
185Black-normal
b+ vg+
b vg b vg
b vg b+ vg
b vg
b vg
b+ vg+
Spermb vg
Parental-type offspring Recombinant offspring
Recombinationfrequency
=391 recombinants
2,300 total offspring 100 = 17%
b vg
b+ vg b vg+
b vg+
Eggs
Recombinantchromosomes
Mapping the Distance Between Genes Using Recombination Data
• A genetic map, an ordered list of the genetic loci along a
particular chromosome
• The farther apart two genes are, the higher the probability
that a crossover will occur between them and therefore the
higher the recombination frequency
• A linkage map is a genetic map of a chromosome based
on recombination frequencies
• Distances between genes can be expressed as map
units; one map unit equals a 1% recombination frequency
• Map units indicate relative distance and order, not precise
locations of genes!
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Recombinationfrequencies
Chromosome
9% 9.5%
17%
b cn vg
Genes that are far apart on the same chromosome can have a recombination
frequency near 50%
Such genes are physically linked, but genetically unlinked, and behave as if found
on different chromosomes• Recombination frequencies were used to make linkage
maps of fruit fly genes on a chromosome.
• Using methods like chromosomal banding, geneticists can
develop cytogenetic maps of chromosomes
• Cytogenetic maps indicate the positions of genes with
respect to chromosomal features
– Genes will have the same order but may have different
distances than a linkage map
Mutant phenotypesShortaristae
Blackbody
Cinnabareyes
Vestigialwings
Browneyes
Redeyes
Normalwings
Redeyes
Graybody
Long aristae(appendageson head)
Wild-type phenotypes
0 48.5 57.5 67.0 104.5
Alterations of chromosome number or structure cause some genetic disorders
• Gross changes to chromosome often lead to spontaneous
abortions (miscarriages) or cause a variety of
developmental disorders
• Major damage to a chromosome
• Extra or missing chromosomes
– Monosomy (2n-1)
– Trisomy (2n+1)
• Remember the Karyotype – looking for missing, extra or
damaged chromosomes?
Alterations of Chromosome Number
• Non-disjunction, pairs of homologous chromosomes fail
to separate normally during meiosis I or II.
• As a result, one gamete receives two of the same type of
chromosome, and another gamete receives no copy.
• Aneuploidy (having an abnormal chromosome #)
results from the fertilization of gametes in which non-
disjunction occurred
• A monosomic zygote has only one copy of a particular
chromosome
• A trisomic zygote has three copies of a particular
chromosome
Meiosis I
(a) Nondisjunction of homologouschromosomes in meiosis I
(b) Nondisjunction of sisterchromatids in meiosis II
Nondisjunction
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Meiosis I
Nondisjunction
(a) Nondisjunction of homologouschromosomes in meiosis I
(b) Nondisjunction of sisterchromatids in meiosis II
Meiosis II
Nondisjunction
Meiosis I
Nondisjunction
(a) Nondisjunction of homologouschromosomes in meiosis I
(b) Nondisjunction of sisterchromatids in meiosis II
Meiosis II
Nondisjunction
Gametes
Number of chromosomes
n + 1 n + 1 n + 1n – 1 n – 1 n – 1 n n
Polyploidy
Polyploidy 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 I’m a tetraploid!
Alterations of Chromosome Structure
• Breakage of a chromosome can lead to four types of
changes in chromosome structure:
– Deletion removes a chromosomal segment
– Duplication repeats a segment
– Inversion reverses a segment within a chromosome
– Translocation moves a segment from one
chromosome to another
DeletionA B C D E F G H A B C E F G H
(a)
(b)
(c)
(d)
Duplication
Inversion
Reciprocaltranslocation
A B C D E F G H
A B C D E F G H
A B C D E F G H
A B C B C D E F G H
A D C B E F G H
M N O C D E F G H
M N O P Q R A B P Q R
Human Disorders Due to Chromosomal Alterations
• Down Syndrome (Trisomy 21)
– ~ 1:700 births in the U.S
– frequency of Down syndrome
increases with the age of the
mother.
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Aneuploidy of Sex Chromosomes
Nondisjunction of sex chromosomes produces a
variety of aneuploid conditions
• Monosomy X (Turner syndrome)
– Monosomy of Sex
Chromosomes; XO female
– Characteristics: Infertile/sterile,
dwarfism, overweight, some
mental retardation, webbed neck,
sterile
– it is the only known viable
monosomy in humans
• XXY (Klinefelter syndrome)
– Feminine characteristics, infertile, unusually tall,
– the result of an extra X chromosome in a male.
Disorders Caused by Structurally Altered Chromosomes
• 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
• Certain cancers, including chronic myelogenous leukemia
(CML), are caused by translocations of chromosomes
Normal chromosome 9
Normal chromosome 22
Translocated chromosome 9
Translocated chromosome 22(Philadelphia chromosome)
Reciprocaltranslocation
Exceptions to the standard chromosome theory
• 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
Genomic Imprinting• The phenotype depends on which parent donated the
alleles for that trait.
• This type of variation is called genomic imprinting
• Silencing occurs when certain genes that are methylated
during gamete production (addition of –CH3) of DNA,
remember this from functional groups. Methylation
silences the expression of that gene.
• Genomic imprinting is thought to affect only a small fraction
of mammalian genes
• Most imprinted genes are critical for embryonic
development
Normal Igf2 allele
is expressedPaternalchromosome
Maternalchromosome
(a) Homozygote
Wild-type mouse(normal size)
Normal Igf2 allele
is not expressed
Mutant Igf2 alleleinherited from mother
Mutant Igf2 alleleinherited from father
Normal size mouse(wild type)
Dwarf mouse(mutant)
Normal Igf2 alleleis expressed
Mutant Igf2 alleleis expressed
Mutant Igf2 alleleis not expressed
Normal Igf2 alleleis not expressed
(b) Heterozygotes
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Inheritance of Organelle Genes
• Extra-nuclear genes (or cytoplasmic genes) are genes found in organelles in the cytoplasm (mitochondria and chloroplasts!)
• Extra-nuclear genes are inherited maternally because the zygote’s cytoplasm comes from the egg
• 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
EggSperm
P generationgametes
CBAD E
F
D
F E
AB
C
e
d
f
c ba
d
f
e
cba
This F1 cell has 2n = 6chromosomes and isheterozygous for all sixgenes shown (AaBbCcDdEeFf).
Red = maternal; blue = paternal.
+
Each chromosomehas hundreds or
thousands of genes.
Four (A, B, C, F) areshown on this one.
The alleles of unlinkedgenes are either on
separate chromosomes
(such as d and e) or sofar apart on the samechromosome (c and f)that they assortindependently.
Genes on the same chromo-
some whose alleles are so
close together that they donot assort independently(such as a, b, and c) are saidto be linked.