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8/13/2019 Genetics Chapter 8
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Changes in Chromosome
Structure and Number
Chapter 8
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Variation in Chromosome Structure:
Inversions
Deletions
Duplications
Translocations
Cytogenetics: study of chromosomenumber and structure
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Variation in Chromosome
Structure
I. Noncentromeric breaks
A. single breaks
1. restitution
2. deletion
3. dicentric bridgeB. two breaks, same chromosome
1. deletion
2. inversion
C. two breaks, nonhomologous chromosomes
1. reciprocal translocation2. dicentric bridge
II. Centromeric breaks
A. fission
B. fusion
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Single Breaks
Results:
Centric and acentric chromosomes
(no consequences in restitution)
does not segregate
properlydegraded
Segregates
normally in
mitosis and
meiosis butlacks telomere;
(occasionally)
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Single Breaks
Results: Dicentric Chromosome
ultimate fate is breakage
bridge
after replication, breakage-fusion-breakage cycle can repeat in eachgeneration, causing more imbalance, ultimately causing cell death
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Robertsonian translocation (fusion):
joining of 2 acrocentric chromosomes
at or near centromeres
Centromeric breaks
(short arms are lost-both lack centromere)
http://www.embryology.ch/anglais/kchromaber/abweichende03.html
produces a decreased # of chromosomes
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Total number,sex chromosomes,changes in autosomes
46,XY
46,XX
Change in total number of chromosomes :
47,XX,+21 : female with extra copy of chromosome 21
Change in part of chromosomes :
p: short arm
q: long arm- here + indicates increase in size, - decrease in size
46,XX,t(9p-;18p+) : female with transfer of part of short arm
of chromosome 9 to short arm of chromosome 18
(; indicates both chromosomes kept centromeres)
Nomenclature
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Deletions
This loss of a portion of a chromosome cannot be regenerated
Analysis of deletion loops allowed the characterization of deletionsassociated with human genetic abnormalities
Result in loss of chromosomal material : centric fragments
remain
Forms a deletion loop at prophase of meiosis I
can be seen next to normal homolog
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Deletion Loop in Polytene
Chromosomes of Drosophila
deletion loop in wild-type homolog
reveals bands that are missing in
the deleted chromosome
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Deletions Can Lead to :
1. Pseudodominance
Recessive alleles are expressed due to deletion ofdominant allele
results in only 1 recessive allele
1. (deletion of a+ to end)
2. (deletion of intervening b+)
useful for deletion mapping : from banding pattern, we know which region is deleted
- phenotype tells us whether wt copy is removed- if wt allele is in deleted regionrecessive phenotype
2 examples :
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Deletion mapping in Drosophila
w : 3C2-4
fa : 3C7
resulting phenotype when deletion
heterozygote is
crossed with wwor fafahomozygote
(complementation test):
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Genetic imbalance : result of having 2 copies ofsome genes and 1 copy (or 3 copies) of other
genes
unnatural ratio of gene expressionreduction can lead to insufficient expression
* large deletions are rare because they are lethal
Haploinsufficiency :deletion results in lethal
phenotype due to expression of only a single
wild type allele
Deletions Can Lead to :
2. Genetic Imbalance
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Large Deletions Can Cause Disorders
or Be Lethal
Cri du Chat
deletion of short arm of chromosome 5 results in microcephaly,congenital heart disease, and mental retardation
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Inversions
1. Break between genes: no effect
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Inversions
2. Break within gene: generates mutant allele
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Inversions
centromere between 2 breaks centromere outside of 2 breaks
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Paracentric Inversion forms inversion loop at
prophase I of heterozygotes
(physical restraint of homolog synapsis
prevents crossovers)
(recombinations in loop produce deletions
and duplicaitons resulting in nonviable
gametes )
synapsis maximizes
pairing of homologous
segments of chromosomes
with a loop
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Paracentric Inversion in
Drosophila
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Suppression of Recombination1. Paracentric inversion : recombination in
inversion loop produces nonviable gametes
both dicentric and acentric chromosomes produced by recombination
produce nonviable gametesno recombinants in offspring)
(recombinant)
(recombinant)
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Nonrecombinant chromosome
Unbalanced chromosome
Nonrecombinant inversion chromosome
Unbalanced chromosome
duplications and deletions in recombinants produce nonviable zygotes(imbalanced gene expression)no recombinants in offspring
2. Pericentric inversion : again, recombination in
inversion loop produces nonviable gametes
Suppression of Recombination
I i d f tilit
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Inversions reduce fertility
half the chromatids produced during recombinationcannot produce viable gametes
however, because recombination outside of inversion
loop is unaffected, > half of all gametes produced arebalanced and produce viable offspring
I i C I ti t All l b
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Inversion Can Inactivate an Allele by
Placing It in Heterochromatic Region
Inversion of the X chromosome in Drosophila:
position effectresults in variegation
- depends on whether
heterochromatin spreadsto w+locus
- can be different for
individual cells in the
eye
The inversion of the white allele on X
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The inversion of the white allele on X
chromosome in Drosophilaplaces it in
heterochromatic region, resulting in variegated
eye color
w+locus (normally in euchromatin) is not expressed in certain cells in the eye
in these cells, an inversion positions it near a region of heterochromatin,
which turns off expression
XwX+genotype - depends on whether heterochromatinspreads to w+locus- can be different for individual eye cells
spreading of heterochromatin :
influenced by environment ?
(epigenetics)
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Translocation
Reciprocal translocation heterozygote :
pairing at meiosis I forms a cross-shaped
structure
Reciprocal translocation : exchange of DNA between 2
nonhomologous chromosomes
R i l T l ti lt
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alternate and adjacent-1 are preferred and equally likely
results in semisterilitybecause 50% of gametes (adjacent-1 segregation)
have unbalanced chromosomes which produce nonviable offspring
Reciprocal Translocation results
in : 1. semisterilitysegregation of translocation heterozygote :
homologous centromeres
segregated ? Yes Yes No
R i l T l ti lt
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genes near breakpoint appear tightly linked, even though they are on
nonhomologous chromosomes
if crossovers occur, only those producing balanced gametes will survive
these will maintain the close association between
the translocated alleles on nonhomologous chromosomes
Reciprocal Translocation results
in : 2. pseudolinkage
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Centromeric Breaks: Fusion and Fission
Robertsonian chromosome : fusion of long arms of 2
nonhomologous chromosomes
- may change chromosome # without changing genetic material
can count # of chromosomal arms instead : fundamental number (NF)
fission: a break at the centromere ; each arm contains
enough centromere sequence to function as an independent
chromosome
(maintained if centromere is preserved)
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Duplications
- Bar Eye mutation in Drosophila
decreases number of eye facets(ommatidia) as # of duplications
increases
occur by :
1. breakage-fusion-bridge cycle
2. crossovers within an inversion loop
3. unequal crossing over
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BarEye in Drosophila
also a posi t ional effect: configuration of B+ allele determines phenotype,
even though both homozygous Bar and heterozygous Doublebar have
4 copies of B+ segment
wt allele (B+) : B+(1 copy of B+allele)
Bar allele (B) : B+B+(2 copies of wt B+gene)
Doublebar allele (BB) : B+B+B+(3 copies of wt B+allele)
U l C I
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Unequal Crossover Increases
Number of Duplications of Bar
Gene in Drosophila
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Fragile X Chromosome in Humans
defect appears to be a break in a region at tip of X chromosome, but
the break is not required for the syndrome
results in mental retardation
chance of inheriting the syndrome increases with each generation
Unequal Crossover Increases
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Unequal Crossover Increases
Number of Triplet Repeats
caused by duplication of a CCG repeat in FMR-1 gene caused by
unequal recombination between homologous chromosomes
>230 copies inactivates the gene, involved in translational suppression
similar mechanism (unstable trinucletoide repeats) as other diseases
such as Huntington disease
V i ti i Ch
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Variations in Chromosome
Number
Anueploidy: variations in the number of single chromosomes(from nondisjunctionor chromosome lagging)
monosomic: missing 1 chromosome nullisomic: missing both copies
trisomic : diploid cell with an extra chromosome
tetrasomic
most aneuploid fetuses spontaneously abort
Euploidy: variation in the number of sets of chromosomes(haploid, diploid, triploid, tetraploid)
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Aneuploids: Nondisjunction of
Sex Chromosomes in Males
*only X and Y
chromosomes are
shown ; human
males have 22 other
pairs
Ane ploids Nondisj nction in
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Aneuploids: Nondisjunction in
Females
*only X
chromosomes are
shown ; human
females have 22 other
pairs
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Aneuploidy : Nondisjunction
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Aneuploids
Sex chromosomes:
XO Turners
XXX Triple X
XXY Klinefelters
XYY Double Y
Autosomes:
Trisomy 21 (47, XX or XY, +21)
- Down Syndrome (sporadic) : increased with older mothers- Familial Down (translocation of 21 to 14 or 15)
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Trisomy 21: Down Syndrome
Karyotype: trisomy 21
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Incidence of Down Syndrome
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Familial Down Syndrome
(Translocation)
Robertsonian translocation:
Fusion of chromosome 14 with
chromosome 21
Aneuploidy in Autosomes:
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Aneuploidy in Autosomes:
Trisomy 18 and Trisomy 13
Trisomy 18 (Edward Syndrome) 47, XX or XY, +18 major heart defects,
displaced liver,
distal joints have limited motion,
severe mental retardation 80-90% mortality by 2 years
Trisomy 13 (Patau Syndrome) 47, XX or XY, +13
small or missing eyes
cleft palate congenital heart defects,
polydactyly
mental retardation
mortality high in first year of life.
Aneuploidy in Sex
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Aneuploidy in Sex
ChromosomesXO : Turners normal intelligence
underdeveloped ovaries, infertility,
abnormal jaws, webbed neck, short in stature
XYY
some speech and reading problems after age 35, extra Y degenerates, no longer passed on
XXY Klinefelters
tall stature, reduced pubic and facial hair
underdeveloped testes, sometimes infertility
problems with behavior and speech development
XXX Triple X
mildly mentally retarded, delayed growth
severity depends on essential genes that are either over- or underexpressed
on the sex chromosomes genetic balance is essential
Aneuploidy in Sex
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XYY XXX
Aneuploidy in Sex
Chromosomes
Mosaicism
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Mosaicism
An organism is made up of cells that contain one or
more different chromosome numbers
- individual has 2 genotypes
produced by
1) mitot ic nondisjunction2) chromosome lagging during mitosis
- example : loss of chromosome early in
development produces a gynandromorphin Drosophila
- part male (X0) and part female (XX)
- in humans : XX/X ; XY/X ; XX/XY ; XXX/X
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Mitotic Nondisjunction
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Chromosome Lagging
D hil G d h I
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Drosophila Gynandromorph Is
1/2 male, 1/2 female(started as female fly, heterozygous for white eye and miniature wing
X-linked genes)
Changes in Euploidy
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Changes in Euploidy
(whole sets of chromosomes)
Autopolyploidy- all of chromosomes comefrom same species
Allopolyploidy- chromosomes come fromhybridization of two different species
P bl ith P l l id
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Problems with Polyploids
General chromosomal imbalance : as withaneuploids, viability of fetus is affected
Disruption of sex determination
Unbalanced gametes (with odd number of
sets of chromosomes)usually produces aneuploid gametes and
nonviable zygotes
an even number of sets is more likely
Segregation Problems with Triploids in
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Segregation Problems with Triploids in
Meiosis
probability of producing a normal gamete = (1/2)n
n= haploid number
(of diagrammed arrangement)
all possible gametes :
Some allopolyploids do not have expected
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Some allopolyploids do not have expected
characteristics :
. . . but others do seedless watermelon (triploid, produced from tetraploid x diploid)
Jumbo Macintosh apples (tetraploid)
~30-80% of all flowering plants (and 95% of ferns) are polyploid
Pl t ft i l l id
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Plants can often survive as polyploids
fewer plants than mammals have chromosomal sex-
determining mechanisms
plants can avoid meiotic complications of polyploidylonger than mammals
- can exist in vegetative state until somatic doubling
occurs to produce an amphidiploid(each
duplicated chromosome now has a meiotic partner)
more opportunity for hybridization (wind, insects)