genetics chapter 8

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


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


- 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



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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)

genetics chapter 8

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