Chromosomal alterations

Question 1

Chromosomal territories

Answer 1

contain a single chromosome within an arbitrary region that is not bound by any membranes

Question 2

karyotype

Answer 2

We can visualise our chromosomes by means of

Question 3

autosomes

Answer 3

Chromosomes 1-22

Question 4

sex chromosome

Answer 4

Chromosome 23 (X and Y, identified separately but together make the homologous 23rd )

Question 5

How are chromosomes divided?

Answer 5

Chromosomes are divided at the centromere into chromosome arms

Usually unequal lengths

Short arm (p arm)

Long arm (q arm)

Question 6

nondisjunction

Answer 6

When chromosomes and sister chromatids fail to separate properly

Question 7

What are the effects of non disjunction?

Answer 7

Affects the numbers of chromosomes within cells

Adds or removes large amounts of genetic material

Usually alters the phenotype, affects development and/or fertility

Bc incorrect dosage compensation

Question 8

euploid

Answer 8

Chromosome numbers that are a multiple of the haploid number (ie 2n, 3n, 4n, etc)

Question 9

aneuploid

Answer 9

If we add or remove a chromosome, it alters the euploid number and generates an

Question 10

aneuploidy

Answer 10

Caused by Nondisjunction in germ-line cells

Question 11

Describe what happens if non disjuniction occurs in meiosis 1

Answer 11

In meiosis I, results in the failure of homologous chromosome separation

Gametes end up with one extra or one missing chromosome

Trisomic (2n+1): three of one chromosome instead of a homologous pair

Monosomic (2n-1): single copy of one of the chromosomes instead of a homologous pair

Question 12

Describe what happens if non disjuniction occurs in meiosis 2

Answer 12

In meiosis II, results in the failure of sister chromatid separation

Typically follows normal meiosis I

Two resulting gametes produce normally

Two resulting gametes become (n+1) and (n-1

After fertilisation, we get: Trisomic (2n+1): three of one chromosome instead of a homologous pair

Monosomic (2n-1): single copy of one of the chromosomes instead of a homologous pair

Question 13

What does aneuploid alter?

Answer 13

changes the gene dosage of all of the genes on the affected chromosome- if we have an extra cope of chromosome 1 we will have extra expression of it

In diploid organisms, gene dosage is 100%

Monosomic individuals, gene dosage is 50%

Trisomic individuals, gene dosage is 150%!

Leads to imbalance of gene products

Question 14

How are plants and animals affected by aneuploidy?

Answer 14

Animals are usually more affected by gene dosage
Developmental delays and/or nervous system underdevelopment due to aneuploidy
Often lethal

Plants are usually a little bit more tolerant of changes in gene dosage
Different developmental programming than animals

Question 15

How does aneuploid affect humans?

Answer 15

We have potentially 24 different kinds of trisomy (one for each autosome, one for X, and one for Y)

Only really see trisomy 13, 18, and 21 and rarely any monosomies in autosomes

Often see trisomies in sex chromosomes

Other trisomies/monosomies usually result in death of the embryo

Developmental abnormalities are so severe, the zygote cannot survive and aborts

Question 16

Trisomy 21 (Down Syndrome)

Answer 16

The most common autosomal aneuploidy in humans

Linked to age of the mother

Meiosis begins in the fetal ovaries, where it reaches synapsis in prophase I and then stops

At puberty, monthly cycles reinitiate meiosis in a few follicles and the egg is released into the fallopian tubes after meiosis I

Meiosis II begins after fertilisation with a sperm

Meisos in female sex cells is very slow

90% of trisomy 21 cases were a result of meiosis I nondisjunction

Progeny have 2 copies of maternal C21, and one copy of paternal C21

Question 17

Turner Syndrome

Answer 17

(X0 females)- monosomy missing an x

Although one X chromosome is normally inactivated to compensate for gene dosage, 2 X chromosomes are still needed for normal development in females

The genes on the single X chromosome in Turner syndrome are not enough for normal development

Results in no secondary sexual characteristics, infertility, short stature, webbed neck

Question 18

Triple X Syndrome

Answer 18

(XXX females)

Tall stature, possible reduction in fertility, menstrual irregularity

May have speech delays

Question 19

Mosaicism

Answer 19

X-inactivation mosaicism

One X chromosome in female somatic cells is randomly inactivated
- condition in which an individual is composed of 2 or more cell types having different genetic or chromosomal makeup

Question 20

How can Mosaicism develop

Answer 20

Mitotic nondisjunction
Occurs during embryogenesis early in development

25-30% of cases of Turner syndrome can result in 45, X0 monosomy and others 46, XX.

Other individuals can also of mosaicism carrying 47, XXX cells

Derived from a 46, XX zygote undergoing nondisjunction

Question 21

Uniparental disomy

Answer 21

both copies of the homologous chromosome pair are derived from the same parent- normally we have one from each parent

Question 22

Polyploidy

Answer 22

s the presence of three or more sets of chromosomes

Very common in plants (3n, 4n 5n, 6n, 8n, 12n, etc)

Question 23

Autopolyploids

Answer 23

have chromosomes derived from a single species

Question 24

Allopolyploids

Answer 24

have chromosomes derived from multiple species

Question 25

What does polyploidy result from?

Answer 25

Results from Meiotic nondisjunction Ie a 2n egg fertilized with a 1n sperm -> 3n plant- polyploid Mitotic nondisjunction Doubles chromosome number (ie a 2n cell undergoing mitosis now becomes 4n)

Question 26

What can changes to chromosome structure result in?

Answer 26

can result in the loss or addition of genes  Causes gene dosage imbalances  Animals greatly affected by this abnormalities

Question 27

Why are Chromosomal mutations are important?

Answer 27

A common source of genetic variation  A major cause of genetic disorders and conditions  A cause of infertility  4 mains kinds of mutations  Deletions, duplications, inversions, translocations

Question 28

When and why do chromosomes break?

Answer 28

may break during DNA synthesis, crossing over during cell meiosis, etc  Breaks may also be due to  External mutagens, chemicals, radiation  Transposable (ie mobile) bits of DNA  Recombination errors  Failure of the chiasma to disconnect puts strain on the chromosome

Question 29

What happens when a break happens?

Answer 29

segments of the chromosome can be lost |  The ends may be “sticky”, allowing them to rejoin the chromosome (or another) in anew configuration

Question 30

Partial chromosome deletion

Answer 30

Both strands of DNA are severed at the chromosome break point  The broken ends retain their chromatin structure Can re-adhere to each other, other truncated chromosomes, or ends of intact chromosomes Breakage can lead to partial deletion of genes on the chromosome Size and number of genes involved in the break are significant factors in phenotypic abnormality

Question 31

Terminal deletion

Answer 31

the part of or the entire chromosomal arm breaks off Contains termini, consisting of a telomere and additional genetic material  Leaves a chromosome fragment acentric (ie without a centromere) Can be lost during cell division Lacks a kinetochore for attaching to the spindle fibers

Question 32

partial deletion heterozygote

Answer 32

where one chromosome is wildtype and the homolog has the terminal deletion  Can also have a normal recessive homolog and the homolog with the terminal deletion  “pseudodominance”  Whichever alleles are on the normal homolog will be phenotypically expressed

Question 33

Interstitial deletion

Answer 33

e can get 2 chromosomal breaks, resulting in the loss of an internal segment internal broken ends are then joined back together, resulting in a short than normal chromosome

Question 34

Why do deletions matter?

Answer 34

Missing a segment of the chromosome Affects gene dosage  Can be lethal If the centromere is lost, chromosome cannot complete meiosis -> huge loss of genetic info If the segment is deleted from both homologous chromosomes, it is a deletion homozygote

Question 35

Duplications

Answer 35

are repeated segments on a chromosome(s)  Can arise from unequal crossing over can change the phenotype  Increased gene dosage  Extra genes can take on new functions in evolutionary time or develop into new gene families  Ex. Globin genes that code for protein subunits  Expression can vary both before and after birth

Question 36

What occurs when unequal crossing over occurs

Answer 36

Partial duplication  Partial deletion  Individual with one wild type chromosome and one with duplicated material is a partial duplication heterozygote  Individual with one wild type chromosome and one with deleted material is a partial deletion heterozygote

Question 37

Why does unequal crossover occur

Answer 37

Unequal crossover is rare and occurs when homologs misalign during prophase I

Question 38

Describe which chromosome is responsible for Williams-Beuren syndrome

Answer 38

ound in partial deletion heterozygotes for chromosome 7  Wildtype chromosome 7 contains duplicate copies of gene PMS, with 17 genes between them  Misalignment of the homologous chromosomes results in mispairing for PMSA and PMSB on the homologs  This forces a copy of each PMS gene to loop out from the homolog during misalignment  Unequal crossing-over occurs, resulting in one homolog having a partial deletion  Contains a hybrid PMSA-PMSB gene and is missing intact copies of the full genes The shortened partial deletion chromosome causes the phenotypic effects in the disorder  The lengthened partial duplication chromosome has no negative phenotypic effects  Still has intact PMSA and PMSB genes, separated by the 17 genes in the middle

Question 39

chromosome inversion

Answer 39

Remember those “sticky ends”?  If they join back to the broken chromosome, but in the wrong orientation (ie 180°), the chromosome produces.... Usually only affects one member of the homologous pair

Question 40

Paracentric inversions

Answer 40

Inversion does not include the centromere |  Occurs on a single arm

Question 41

Pericentric inversions:

Answer 41

Inversion includes the centromere |  Appears to “rotate” on the centromere

Question 42

Inversion homozygotes

Answer 42

still have all genes and a normal phenotype unless:  Inversion break disrupts a coding region  Position along the chromosome affects gene expression

Question 43

Inversion heterozygotes

Answer 43

have one normal chromosome and one inverted chromosome still have all genes and a normal phenotype but:  The inversion is mismatched with regular meiotic pairing  Inversion loops form during meiosis  Viability of gametes and fertility is reduced due to crossing over events within the inversion

Question 44

Describe crossing over in paracentric/ paracentric inversion

Answer 44

Crossing over occurs inside the region of the inversion loop  Results in duplications and deletions in recombinant chromosomes  If crossing over occurs outside of the inversion loop, all is normal and good (ie reciprocal) Result : 2 paranental- 1 nor mal 1 inverted- viable 2 recombinants- inviable

Question 45

i

Answer 45

1. Theprobabilityofcrossoverwithintheinversionloopislinkedtothesizeofthe inversion loop  Small inversions produce small loops, which have a low frequency of cross over 2. Inversionsuppressestheproductionofrecombinantchromosomes  Viable gametes produced by inversion heterozygotes contain either the normal-order chromosome, or the inverted chromosome No recombinant chromosomes in progeny! -> crossover suppression 3. Fertility may be altered if an inversion heterozygote carries a very larger inversion  If an inversion spans a great length of the chromosome, any crossover will produce 2 viable gametes and 2 nonviable recombinant gametes

Question 46

translocation

Answer 46

When a chromosome breaks and the fragment reattaches to a different chromosome (ie a nonhomologous chromosome) or to a new spot on the same chromosome,

Question 47

Translocation heterozygotes

Answer 47

have one normal chromosome and one altered chromosome

Question 48

 Unbalanced translocation

Answer 48

reattachment to a new chromosome (a one-way event)

Question 49

Reciprocal translocation:

Answer 49

two chromosomes swap fragments with each other (a two-way event) A form of Down Syndrome is caused for the reciprocal translocation of chromosome 14 and 21

Question 50

Robertsonian translocation

Answer 50

(chromosome fusion): two nonhomologous chromosomes fuse together, with the loss of one of the centromeres

Question 51

Alternate segregation

Answer 51

will move chromosomes I and IV to opposite poles and II and III to opposite poles

Question 52

Adjacent segregation

Answer 52

will move chromosomes I and III to opposite poles and II and IV to opposite poles

Question 53

Why do translocations matter?

Answer 53

``` Associated with many types of cancers Leukemia (chronic myelogenous) Interrupts a gene required in the cell cycle regulation (checkpoints)  Genomic instabilities Can lead to other cancers Due to mutations in DNA repair genes ```