The Chromosomal Basis of Inheritance
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Transcript The Chromosomal Basis of Inheritance
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 q2 wks
4 chromosomes (3 pair autosomes/1 pair sex
chromosomes)
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
any alternative is mutant phenotype
symbols:
w+
wild type (“w” for white eyes)
Morgan’s Experiment
mated white eyed male x w+ female
Morgan’s Experiment
white-eyed trait showed up only in male offspring:
100% F2 females red eyes
50% F2 males white eyes/ 50% red eyes
suggested that gene for eye color located on X
chromosome
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
very few genes on Y chromosome so very few
Y-linked
most related to male-ness
rare example
produces abnl sperm
X-Linked Genes
~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
3. Hemophilia
1.
X Chromosome Inactivation in Female Mammals
1 of the 2 X’s in females becomes inactivated
during embryonic development
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
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
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
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 testcrtoss
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
Genetic Disorders due to Chromosomal Abnl
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
Nondisjunction
when any of the gametes in last slide go thru
fertilization zygote with abnl # 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
Which is polyploid?
Alterations of Chromosome Structure
breakage in chromosome can lead to 4 types
of changes:
1. deletion: chromosome fragment is lost
2. duplication: “deleted” fragment attaches to
some other chromosome
3. inversion: fragment reattaches to original
chromosome but is in reverse orientation
4. 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 Features
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
1/1000 live male births
normal sexual
development
somewhat taller
not a well-defined
syndrome
XXX
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
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