CAMPBELL & REECE CHAPTER 15 The Chromosomal Basis of Inheritance.
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Transcript of CAMPBELL & REECE CHAPTER 15 The Chromosomal Basis of Inheritance.
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CAMPBELL & REECECHAPTER 15
The Chromosomal Basis of
Inheritance
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Chromosome Theory of Inheritance
1860: Mendel1875: stages of mitosis1890: stages of meiosis1902: Walter Sutton & Theodor Boveri noted
parallels between Mendel’s “factors” & what chromosomes do in mitosis & meiosis
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Chromosome Theory of Inheritance
Chromosomes & genes are present in pairs in diploid cells
Homologous chromosomes separate during meiosis
Fertilization restores chromosomes to 2nChromosomes segregate & assorts
independently
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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)
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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
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Morgan’s Experiment
wild type: the phenotype for a character most commonly observed in natural populations
any alternative is mutant phenotypesymbols:
w+ wild type (“w” for white eyes)
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Morgan’s Experiment
mated white eyed male x w+ female
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Morgan’s Experiment
white-eyed trait showed up only in male offspring:
100% F2 females red eyes50% F2 males white eyes/ 50% red eyes
suggested that gene for eye color located on X chromosome
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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
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Other Chromosomal Systems of Sex Determination
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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-nessrare example
produces abnl sperm
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X-Linked Genes
~1,100 genesmany unrelated to sex
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X-Linked Recessive Traits
terms homozygous * heterozygous lack meaning when describing X-linked genes
males only have 1 copyfemales will have 2 copies
rare, but not impossible for female to show recessive phenotype
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X-Linked Recessive Disorders
1. Color-blindness2. Duchenne Muscular Dystrophy3. Hemophilia
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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
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Barr Bodies
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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
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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
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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
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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
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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
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Cross of hybrid parents
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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
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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
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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
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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
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Genetic Disorders due to Chromosomal Abnl
large-scale chromosomal changesmany abortion of fetus (spontaneous
miscarriage)Chromosomes can be damaged:
in meiosis by chemical or physical means
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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
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Nondisjunction in Meiosis I
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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
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Aneuploidy
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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
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Polyploidy
2 or more complete sets of chromosomes in all somatic cells:
3n = triploidy4n = tetraploidyindividuals appear more normal than having 1
extra or 1 missing chromosomecommon in plant kingdom3n: bananas6n: wheat8n: strawberriesanimal kingdom: few examples: fish &
amphibians
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Which is polyploid?
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Alterations of Chromosome Structure
breakage in chromosome can lead to 4 types of changes:
1. deletion: chromosome fragment is lost2. duplication: “deleted” fragment
attaches to some other chromosome3. inversion: fragment reattaches to
original chromosome but is in reverse orientation
4. translocation: fragment joins a nonhomologous chromosome
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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
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Human Disorders due to Chromosomal Alterations
Trisomy 21 (Down Syndrome)1/700 children born in USAeach 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
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Trisomy 21 Features
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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 yearPrenatal screening offered to women in
pregnancy
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Aneuploidy in Sex Chromosomes
less likely to be lethal than in autosomesKlinefelter Syndrome:
XXY 1/500 to 1/1000 live male births phenotype: male sex organs, sterile, small
testes, tall stature, +/- subnormal intelligence, +/- breast enlargement
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XYY
1/1000 live male births
normal sexual development
somewhat tallernot a well-defined
syndrome
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XXX
1/1000 live female birthshealthy with no unusual physical featuressomewhat taller than average
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XO Turner’s Syndrome
1/2500 live female births*only known viable human monosomysterile because their sex organs do not
maturegiven estrogen replacement to develop
secondary sex characteristicsnormal intelligence
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Cri du Chat
deletion in chromosome 5severely intellectually disabledsmall head with unusual facial featurescry that sounds like cat in distress
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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
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Exceptions to Standard Mendelian Inheritance
Genomic Imprintingmost 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
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Genomic Imprinting
occurs during gamete formation & results in silencing a particular allele of certain genes
genes imprinted differently in sperm & ovazygote expresses only 1 allele of imprinted gene:
the 1 inherited from the female or male parentimprints transmitted to all somatic cells during
developmentgamete-producing cells “erase” the imprints &
the chromosomes of the developing gametes are newly imprinted according to the sex of the person making the gametes
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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
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Inheritance of Organelle Genes
extranuclear genes found in organelles: mitochondria & chloroplasts
plastids found in some plantsorganelles reproduce themselves &
transmit their genes to daughter organelle
organelle genes do not display Mendelian inheritance
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