CAMPBELL & REECECHAPTER 15

The Chromosomal Basis of

Inheritance

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

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

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 phenotypesymbols:

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 eyes50% 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-nessrare example

produces abnl sperm

X-Linked Genes

~1,100 genesmany unrelated to sex

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

X-Linked Recessive Disorders

1. Color-blindness2. Duchenne Muscular Dystrophy3. Hemophilia

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 changesmany 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 = triploidy4n = tetraploidyindividuals appear more normal than having 1

extra or 1 missing chromosomecommon in plant kingdom3n: bananas6n: wheat8n: strawberriesanimal 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 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

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 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

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 yearPrenatal screening offered to women in

pregnancy

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

XYY

1/1000 live male births

normal sexual development

somewhat tallernot a well-defined

syndrome

XXX

1/1000 live female birthshealthy with no unusual physical featuressomewhat taller than average

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

Cri du Chat

deletion in chromosome 5severely intellectually disabledsmall head with unusual facial featurescry 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 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

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

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 plantsorganelles reproduce themselves &

transmit their genes to daughter organelle

organelle genes do not display Mendelian inheritance