Variations In Chromosome Number And Arrangement

Front 1

What are the types of chromosome aberrations?

Back 1

1. Numerical aberrations

2. Structural aberrations

Front 2

What are the types of numerical aberration?

Back 2

1. Polyploidy - multiples of 'n'

2. Aneuploody - 2n ± 'x'

Front 3

What are the types of structural aberrations?

Back 3

1. Deletions

2. Duplications

3. Inversions

4. Translocations

Front 4

What is polyploidy?

In what types of animals does this usually occur?

Back 4

Where the entire chromosomal genome is replicated a number of times.

Occurs more commonly in vertebrates and causes prenatal death in mammals.

Front 5

Describe an aneuploidy.

Back 5

Numerical chromosomal aberration where the chromosomal number is not an exact multiple of the haploid number - 2n ± x

Front 6

Why does an aneuploidy arise?

Back 6

Arises due to non dysjunction events where a chromosome fails to segregate properly during cell division.

Front 7

What types of aneuploidy arise more commonly?

Back 7

Monosomies (2n-1) are generally less well tolerated than trisomies (2n+1)

Front 8

What is the basic principle of the spindle assembly checkpoint?

Back 8

A surveillance mechanism which prevents chromosome mis-segregation.

Front 9

What are the types of anomalous attachments which can occur in spindle assembly?

Back 9

1. Syntelic attachment

2. Monotelic attachment

Front 10

Describe a syntelic attachment.

Back 10

Both kinetochores attached to the same centrosome's microtubules

Front 11

Describe a Monotelic attachment

Back 11

Only one kinetochore is attached to microtubules

Front 12

How does the spindle assembly checkpoint work?

Back 12

Long chain of proteins which are activ until tension in the kinetochore. When the kinetochore is tense it results in the dissolution of the mitotic checkpoint complex.

If there is no tension the complex arrests mitosis.

Front 13

What is Mosaic Variegated Anueplloidy?

Back 13

Genetic mutations in the mitotic regulatory kinase (BUBR1 - A part of the mitotic checkpoint complex) are associated with cancer susceptible disorders.

Front 14

Why are monosomies only seen in sex chromosomes?

Back 14

Due to dosage compensation which is usually seen in X chromosomes but not autosomes.

Front 15

Define haplo insufficiency.

Back 15

Single gene copy may not produce enough proteins to make up for lost allele.

Front 16

Define Hemizygous.

Back 16

Remaining genes may include formerly recessive lethal alleles

Front 17

How does a mosaic individual arise?

Back 17

Mitotic errors during early development.

Front 18

What does a loss of an X chromosome result in?

Back 18

45, x - Female with a single X - Turner's Syndrome

45, y - lethal

Front 19

How does Turner's syndrome arise?

Back 19

Meiotic error causing loss of an x chromosome which commonly occurs during spermatogenesis.

Front 20

Define a trisomy.

Back 20

An addition of an extra chromosome - 2n+1

Front 21

What kinds of trisomys are accepted and not accepted?

Back 21

Addition of large chromosomes is usually lethal

Birth survival trisomies = 21, 18 and 13.

Front 22

What are the 3 main diseases which reuslt from sex chromosomes?

Back 22

1. Klinefelter Syndrome : 47, XXY / 48, XXXY / 49 XXXXY

2. XYY Syndrome: 47, XYY

3. Triple X syndrome: 47, XXX

Front 23

What are the symptoms of Klinefelter syndrome?

Back 23

1. Gynaecomastia

2. Elongated forearms and lower legs

3. Small testes

Front 24

What are the symptoms of XYY syndrome?

Back 24

1. V. tall stature

2. Large teeth

3. Learning disabilities

4. Motor coordination problems

Front 25

What are the classic autosome trisomys?

Back 25

1. Patau syndrome - 47, 13+ (trisomy 13)

2. Edward syndrome - 47, 18+ (trisomy 18)

3. Down Syndrome - 47, 21+ (trisomy 21)

Front 26

What are the symptoms of:

1. Patau syndrome

2. Edward syndrome

?

Back 26

1. Congenital organs malformation

2. Heart defects / severe developmental impairment

Front 27

What gene is at the root cause of down syndrome?

Back 27

The replication of the Down Syndrome Critical Region (DSCR) on chromosome 21.

Front 28

What is the root cause of down syndrome?

Back 28

Inappropriate chromosome replication in the ovum is the source in 95% of cases.

Front 29

Explain, in detail, the effect of maternal age on down syndrome and non disjunction events.

Back 29

Nondisjunction is more likely to occur during oogenesis in the mother.

1. Ova maturation is arrested @ meiosiss II after puberty with the final cell division occuring when the ova is fertilised

2. Therefore each ova is one month older than the last - @ 30-40 y/o the ova are significantly older

3. As the female gets older the meiotic checkpoint components suffer from decay

4. This causes a less efficient process of correcting aneuploidy.

Front 30

What do chromosomal structural abnormalities arise from?

Back 30

Result from chromosomal breakage and inappropriate relinkage of sticky ends to other broken ends.

Front 31

What does chromosome breakage frequency increase with?

Back 31

1. Exposure to ionising radiation

2. Exposure to some chemical mutagens

3. Some rare inherited disorders

Front 32

What are the 5 types of chromosomal abnormality?

Back 32

1. Deletions

2. Duplication

3. Inversion

4. Non reciprocal

5. Reciprocal

Front 33

Describe the genetic cause of Cri du Chat syndrome.

Back 33

Variable deletion of termina portion of chromosome 5.

Deletes hTERT gene - a gene which regulates telomere maintenance.

Front 34

Describe the genetic cause of WAGR syndrome.

Back 34

Interstitial deletion of chromosome 11 p1.3.

Front 35

What are the symptomatic manifestations of:

1. Cri du chat syndrome

2. WAGR syndrome

?

Back 35

1. Malformed larynx (eerie cry which "sounds like a cat") , learning difficulties,

2. Wilms tumour (=mental retardation), Eye problems, Prosis.

Front 36

What type of chromosome abnormality is familial down's syndrome occur as a result of?

Back 36

A Robertsonian Translocation

Front 37

Describe a robertsonian translocation.

Back 37

Results when two non homologous chromosomes undergo a central break and then incorrectly rejoining the acentric fragments together via centric fusion into a small chromosome which is usually lost. The remaining two fragments join and form a large chromosome.

Front 38

Describe the genetic cause of chronic myelogenous leukaemia (CMK)

Back 38

Formation of philadelphia chromosomes by a reciprocal translation of the q arms - creation of oncogenic BCR-ABL fusion gene .

Front 39

How can autosomal aneuplodies be investigated?

Back 39

No dosage compensation in autosomes so tracking of the RNA copy number can allow easy investigation.

Front 40

Why do aneuplodies cause more severe effects when affecting structural genes?

Back 40

Aneuploidy affects structural genes far more than defects of enzymes in a pathway as there is a far less effect of an individual [enzyme] in a very large enzymatic pathway (as many metabolic pathways are)

Front 41

What can aneuploidy in cells lead to an upregulation of?

Back 41

1. DNA damage response - apoptosis

2. Increase in factors involved in the response to oxidative stress & amino acid biosynthesis.

3. Envionmental stress response - causing a decrease in cell growth / proliferation genes and an increase in stress response genes.