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The Chromosomal Basis
of
Inheritance
CAMPBELL & REECE
CHAPTER 15
Chromosome Theory of Inheritance
 1860: Mendel
 1875: stages of mitosis
 1890: stages of meiosis
 1902: Walter Sutton & Theodor Boveri noted
parallels between Mendel’s “factors” & what
chromosomes do in mitosis & meiosis
Chromosome Theory of Inheritance
 Chromosomes & genes are present in pairs in diploid
cells
 Homologous chromosomes separate during meiosis
 Fertilization restores chromosomes to 2n
 Chromosomes segregate & assorts independently
Morgan’s Experiment
 provided 1st evidence that associated specific
gene with specific chromosome
 Drosophila melanogaster (fruit flies)




100’s offspring from 1 mating
new generation 2 wks
4 chromosomes (3 pair autosomes/1 pair sex
chromosomes)
BOZEMAN
Morgan’s Experiment
 after months of mating & inspecting each fly Morgan
finally got what he wanted:
 normally fruit flies have red eyes; now he had one
with white eyes
Morgan’s Experiment
 wild type: the phenotype for a character
most commonly observed in natural
populations

symbols:
w+
wild type (red eyes)
 any alternative is mutant phenotype
 symbols:
w
wild type (white eyes)
Morgan’s Experiment
 mated white eyed male with a
red eyed (w+) female


First generation: all red eyes (red is
dominant)
Second generation: 3:1

BUT the ratios were different
 white-eyed trait showed up only
in male offspring:
 100% F2 females red eyes
 50% F2 males white eyes/ 50% red
eyes

Conclusion
 Eye color was linked to X sex
genes
Gene Linkage
 Linked Genes: genes located near each other
on same chromosome & tend to be inherited
together in genetic crosses
 results of genetic crosses deviate from what
is expected using the Law of Independent
Assortment
How Linkage Affects Inheritance
 Morgan’s Drosophila experiments:
 Wild-type flies have gray bodies & normal-sized wings
 thru breeding Morgan produced flies with black bodies &
much smaller wings (vestigial wings)
 both characters have genes not on the X chromosome &
both are recessive to the wild type
He bred black vestigial wings with gray normal wing
 Produced dihybrids (wild type in appearance, but carried
mutant gene)
 Crossed female dihybrid with true breeding double mutant male
 Expected Medelian results, but didn’t get that (9:3:3:1)
 Conclusion:
 Body color and wing size are usually inherited together in
specific combinations

Morgan’s Experiments with Linkage
 results had much higher proportion of the
combinations of traits seen in P generation flies than
would be expected if the 2 genes assorted
independently
 Again, Morgan concluded that body color & wing size
are usually inherited together in parental
combinations because the genes for these characters
are near each other on the same chromosome
Genetic Recombination
 production of offspring with combinations of traits
that differ from those found in either parent
 occurs with unlinked genes in simple dihybrid cross
of parents heterozygous for the 2 characters
phenotypes that match those of the parents called:
parental types
 phenotypes that do not match those of parents called:
recombinant types or recombinants
 if 50% of offspring are recombinants: 50% frequency of
recombination: will see 50% if the 2 genes in testcross are
on different chromosomes

Cross of hybrid parents
Recombination of Linked Genes
 back to Morgan’s flies: saw >50% (most)
offspring with parental types so conclude
these genes are linked
 What about the 17% that were recombinants?
 Answer: Crossing Over (1st proposed by
Morgan)

proteins in Prophase I orchestrate an exchange
of corresponding segments of 1 maternal
chromosome with its homolog
Recombinant Chromosomes add to Genetic Variation
 many new genetic variations possible thru
crossing over
 random fertilization then increases even
further the # of variant allele combinations
that can be created
Mapping Distances between Genes
 genetic map: an ordered list of the genetic
loci along a particular chromosome
 1st done by Sturtevant (student of Morgan)
hypothesized the % of recombinant offspring
(recombination frequency) depends on the
distance between genes on a chromosome
 assumed crossing over a random event, equally
likely to occur anywhere along length of a
chromosome

Linkage Map
 Sturtevant predicted that the farther apart 2 genes are,
the higher the probability that a crossover will occur
between them & therefore the higher the recombination
frequency.
 Linkage Map: genetic map based on recombination
frequencies
 Map Unit: distances between genes with:
 1 map unit = 1% recombinant frequency
 Observed frequency of recombination in
crosses involving linked genes can have a
maximum value of 50%, or the genes would
be on different chromosomes
Linkage Maps
b-vg recombination frequency is slightly less than the
sum of the b-cn and cn-vg frequencies because double
the crossovers are fairly likely to occur between b and
vg in matings tracking these two genes.
Sex-Linked Genes: Unique Patterns of
Inheritance
 in mammals:
 ova: 1 X chromosome
 sperm: 50% X chromosome/ 50% Y chromosome

short segments of X & Y are homologous & there is
opportunity for crossing over in Prophase I
Other Chromosomal Systems of Sex
Determination
Sex-Linked Gene
 any gene located on either sex chromosome
 Gene on y chromosome required for testes
development (SRY)

SRY gene codes for proteins that regulate other genes
 very few genes on Y chromosome so very few
Y-linked

most related to male-ness
rare
example
produces
abnormal sperm
X-Linked Genes
 Sex-linked genes: genes on either sex
chromosome chromosome

Historically referred to genes on the x chromosome
~1,100 genes
 many unrelated to sex

X-Linked Recessive Traits
 terms homozygous & heterozygous lack meaning
when describing X-linked genes
 males only have 1 copy
 females will have 2 copies

rare, but not impossible for female to show recessive
phenotype
X-Linked Recessive Disorders
Color-blindness
2. Duchenne Muscular
Dystrophy
1.

1/3500 males in the US

Weakening of muscles, loss of
coordination
3. Hemophilia
 Absences of 1+ proteins
required for blood clotting
X Chromosome Inactivation in Female Mammals
 1 of the 2 X’s in females becomes inactivated
during embryonic development

Cells of females and males have the same effective
dose (one copy) of genes with loci on the x
chromosome
 Barr body: inactive X condenses, found
along inside edge of nuclear envelope
 selection of which X will inactivate occurs
randomly & independently in each embryonic
cell …. females are a mosaic of the 2 X
chromosomes
Barr Bodies
Inactivating an X
 involves modification of DNA & the histone proteins
bound to it (includes attachment of methyl groups, --CH3)

Several genes on each X involved in inactivation process
XIST gene (X-inactive specific transcript) becomes active only on
the X that will become the Barr body
 Still being investigated for further understanding

Genetic Disorders due to Chromosomal Abnormality
 large-scale chromosomal changes
 many  abortion of fetus (spontaneous miscarriage)
 Chromosomes can be damaged:
in meiosis
 by chemical or physical means

Abnormal Chromosome #
 occasionally, meiotic spindle does not
distribute chromosomes equally

nondisjunction: an error in meiosis or mitosis in
which members of a pair of homologous
chromosomes or a pair of sister chromatids fail to
separate properly from each other
Nondisjunction in Meiosis I
 when any of the gametes
to the right go thru
fertilization

zygote with abnormal # of a
particular chromosome:
condition called aneuploidy
if 1 gamete has 0 copies of
chromosome the aneuploid
zygote is said to be
monosomic for that
chromosome
 if 1 gamete has 2 copies of
chromosome the aneuploid
zygote is said to be trisomic
for that chromosome

Aneuploidy
Aneuploidy
 Mitosis will subsequently transmit the anomaly to all
embryonic cells


most of these zygotes will end in spontaneous abortion
those that survive it has characteristic set of traits (syndrome)
 If nondisjunction takes place during mitosis in early
embryonic development  passed to large # of cells
& is likely to have substantial effect on organism
Polyploidy
 2 or more complete sets of chromosomes in all
somatic cells:
3n = triploidy
4n = tetraploidy
 individuals appear more normal than having 1 extra
or 1 missing chromosome
 common in plant kingdom
3n: bananas
6n: wheat
8n: strawberries
 animal kingdom: few examples: fish & amphibians
Alterations of Chromosome Structure
 breakage in chromosome can lead to 4
types of changes:
1.
2.
3.
4.
deletion: chromosome fragment is lost
duplication: “deleted” fragment attaches to some
other chromosome
inversion: fragment reattaches to original
chromosome but is in reverse orientation
translocation: fragment joins a nonhomologous
chromosome
Alterations in Chromosome Structure
 deletions & duplications likely to occur
during meiosis


sometime crossing over exchange unequal fragments
If missing any # of essential genes condition is usually
lethal
 translocations & inversions can alter
phenotype because a gene’s expression
can be influences by its location among
neighboring genes
Human Disorders due to Chromosomal Alterations
 Trisomy 21 (Down Syndrome)
 1/700 children born in USA
 each have 47 chromosomes (extra 21st)
 characteristic facial features

short stature, treatable heart defects, developmental
delays, increased risk of leukemia, Alzheimer’s disease,
and a lower rate of hypertension, atherosclerosis, stroke,
many types of solid tumors
Trisomy 21
 frequency of having baby with trisomy 21 increases




with age of mother
<30 years old: found in 0.04% of babies
40 years old: found in 0.92%
>40 risk increases every year
Prenatal screening offered to women in pregnancy
Aneuploidy in Sex Chromosomes
 less likely to be lethal than in autosomes
 Klinefelter Syndrome:
XXY
 1/500 to 1/1000 live male births
 phenotype: male sex organs, sterile, small testes,
tall stature, +/- subnormal intelligence, +/breast enlargement

XYY (Klinefelter Syndrome)
 1/1000 live male births
 normal sexual
development
 somewhat taller
 not a well-defined
syndrome
XXX (Trisomy X)
 1/1000 live female births
 healthy with no unusual physical features
 somewhat taller than average
XO (Turner’s Syndrome)
 1/2500 live female births
 *only known viable human monosomy
 sterile because their sex organs do not
mature
 given estrogen replacement to develop
secondary sex characteristics
 normal intelligence
Cri du Chat
 deletion in chromosome 5
 severely intellectually disabled
 small head with unusual facial features
 cry that sounds like cat in distress
Philadelphia Chromosome
 shortened chromosome 22 due to
translocation of fragment with chromosome
9 during mitosis in WBC production
 individuals have higher incidence of CML by
activating a gene that leads to uncontrolled
cell cycle progression
Exceptions to Standard Mendelian Inheritance
 Genomic Imprinting
 variation in phenotype depending on which parent it
was inherited from
 most of the time it does not matter whether a
particular gene was inherited from mother or
father
 2 – 3 dozen traits in mammals that depend on
whether an allele is inherited from the male
or female parent = genomic imprinting
 most of these genes are on autosomes
Genomic Imprinting
 occurs during gamete formation & results in




silencing a particular allele of certain genes
genes imprinted differently in sperm & ova
zygote expresses only 1 allele of imprinted gene: the 1
inherited from the female or male parent
imprints transmitted to all somatic cells during
development
gamete-producing cells “erase” the imprints & the
chromosomes of the developing gametes are newly
imprinted according to the sex of the person making
the gametes
Imprinted Genes
 1 of 1st identified: mouse gene for insulin
growth factor 2 (Igf2)
 -CH3 groups added to cytosine nucleotides of
1 of allele seems to silence the allele (in some
genes it activates the gene)
 found in small fraction of mammalian genes
but most known one critical for embryonic
development
Inheritance of Organelle Genes
 extranuclear genes found in organelles:
mitochondria & chloroplasts
 plastids found in some plants
 organelles reproduce themselves & transmit
their genes to daughter organelle
 organelle genes do not display Mendelian
inheritance