Download 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