SU2.2

Question 1

What is the suitable size range of genetic variation for chromosome studies?

Answer 1

Chromosome studies are suitable for larger variations, ranging from 10 kilobases (kb) to a full chromosome.

Question 2

An ‘acquired’ genetic variation that results in a mosaic individual depends on the _____ of the variation.

Answer 2

timing

Question 2

What is a ‘constitutional’ genome variation?

Answer 2

It is a genetic variation that is present in all nucleated cells of an individual.

Question 3

What is the approximate resolution of karyotyping for detecting chromosome abnormalities?

Answer 3

The resolution for karyotyping is approximately 1 to 5 megabases (Mb).

Question 3

What are the two main types of variation that chromosome studies can detect?

Answer 3

Chromosome studies can detect numerical and structural variations.

Question 4

Which microscopy-based technique has a resolution of 100kb – 1Mb for detecting chromosome variation?

Answer 4

Fluorescence In Situ Hybridization (FISH).

Question 5

For detecting smaller variations in the range of 10 – 50kb, which molecular technique is employed?

Answer 5

Array technologies are used for detecting variations in the 10 – 50kb range.

Question 6

Which molecular technique is used for detecting the smallest variations, typically in the range of 1 – 100bp?

Answer 6

Sequencing is used for detecting variations in the 1 – 100bp range.

Question 7

What defines a ‘balanced’ structural chromosome rearrangement?

Answer 7

A balanced rearrangement is one where there is no net gain or loss of DNA.

Question 8

Name the two types of balanced structural rearrangements.

Answer 8

The two types are inversions (pericentric and paracentric) and translocations (reciprocal and Robertsonian).

Question 9

What defines an ‘unbalanced’ structural chromosome abnormality?

Answer 9

An unbalanced abnormality involves a net gain or loss of DNA.

Question 10

List three examples of unbalanced structural chromosome abnormalities.

Answer 10

Examples include deletions, duplications, insertions, ring chromosomes, isochromosomes, and markers.

Question 11

Are individuals with balanced structural rearrangements typically symptomatic or asymptomatic?

Answer 11

Individuals with balanced structural rearrangements are often asymptomatic.

Question 12

How can a balanced rearrangement cause a disease phenotype despite no net loss or gain of DNA?

Answer 12

The breakpoints of the rearrangement can disrupt a gene or its regulatory regions.

Question 13

What is a major reproductive consequence for carriers of balanced structural rearrangements?

Answer 13

They can produce both balanced and unbalanced gametes, leading to an increased risk of miscarriage, infertility, or affected offspring.

Question 14

Why are most unbalanced structural rearrangements unviable?

Answer 14

They are usually unviable due to the gain or loss of large amounts of DNA

Question 15

What are potential consequences if a small, unbalanced rearrangement is viable?

Answer 15

It could lead to developmental abnormalities, genetic disorders, reproductive consequences, or cancer.

Question 16

What is the genetic basis of DiGeorge syndrome?

Answer 16

DiGeorge syndrome is caused by a 22q11.2 microdeletion.

Question 17

Cri du Chat syndrome is caused by which specific microdeletion?

Answer 17

It is caused by a 5p deletion.

Question 18

What underlying event on a single chromosome can lead to a deletion, inversion, or ring chromosome?

Answer 18

Two double-strand breaks on one chromosome followed by incorrect repair.

Question 19

What structure forms during meiosis in an individual with a chromosome inversion?

Answer 19

An inversion loop forms during meiosis to allow homologous regions to pair up.

Question 20

A crossover within the inversion loop of a _____ inversion can lead to gametes with deletions and duplications.

Answer 20

pericentric

Question 21

What are the four potential chromosome constitutions in gametes after a crossover in a paracentric inversion loop?

Answer 21

Normal, inverted, dicentric, and acentric chromosomes.

Question 22

What molecular event leads to a translocation?

Answer 22

Double-strand breaks in two different chromosomes followed by incorrect repair and exchange of fragments.

Question 23

What is the term for the structure formed during meiosis in a carrier of a reciprocal translocation?

Answer 23

A quadrivalent structure is formed.

Question 24

What are the three potential outcomes for the offspring of a translocation carrier?

Answer 24

The offspring could be normal, a balanced carrier, or inherit severe chromosomal abnormalities that often result in miscarriage.

Question 25

What are the potential outcomes for the offspring of a Robertsonian translocation carrier?

Answer 25

The offspring could be normal, a balanced carrier, or inherit trisomies or monosomies.

Question 26

Define an isochromosome.

Answer 26

It is a chromosome where either the long arms or the short arms are duplicated to form mirror images of each other.

Question 27

What type of centromere division leads to the formation of an isochromosome?

Answer 27

The centromere divides transversely instead of longitudinally.

Question 28

What is a variant of Turner syndrome caused by an isochromosome?

Answer 28

The variant is 46,X,i(Xq), involving an isochromosome of the long arm of the X chromosome.

Question 29

In which context, besides congenital disorders, can isochromosomes be found?

Answer 29

Isochromosomes, such as i(17q), can be found in some cancers.

Question 30

Polyploidy

Answer 30

A numerical chromosomal abnormality involving the gain or loss of an entire set of chromosomes (e.g., triploidy 3n, tetraploidy 4n).

Question 31

Aneuploidy

Answer 31

A numerical chromosomal abnormality involving the gain or loss of a single autosome or sex chromosome (e.g., trisomy, monosomy).

Question 32

Mixoploidy

Answer 32

The presence of two or more cell populations with different chromosome numbers within the same individual.

Question 33

What is the typical viability of autosomal monosomies?

Answer 33

Autosomal monosomies are almost always unviable and lead to early pregnancy loss.

Question 34

Name the three autosomal trisomies that are considered viable.

Answer 34

Trisomy 13 (Patau syndrome), Trisomy 18 (Edwards syndrome), and Trisomy 21 (Down syndrome).

Question 35

Why do sex chromosome aneuploidies typically have milder effects than autosomal aneuploidies?

Answer 35

This is due to X-inactivation limiting gene dosage and the low gene density of the Y chromosome.

Question 36

What is the chromosome constitution for Turner syndrome?

Answer 36

45,X.

Question 37

What is the chromosome constitution for Klinefelter syndrome?

Answer 37

47,XXY.

Question 38

What is the chromosome constitution for Jacobs syndrome?

Answer 38

47,XYY.

Question 39

What are the two primary mechanisms that cause the addition or loss of a single chromosome, leading to aneuploidy?

Answer 39

Nondisjunction (during meiosis or mitosis) and anaphase lag.

Question 40

What is the outcome if nondisjunction occurs during mitosis after fertilisation (post-zygotic)?

Answer 40

It results in mixoploidy, creating a mosaic of normal and aneuploid cells.

Question 40

A woman has a child with Turner syndrome. One possible cause is _____ during meiosis, resulting in a gamete with 22 chromosomes which is then fertilised.

Answer 40

nondisjunction

Question 40

What is the chromosomal content of gametes resulting from nondisjunction during meiosis?

Answer 40

The resulting gametes will have an abnormal number of chromosomes, such as 22 or 24.

Question 41

What is the key difference between mosaicism and chimerism in terms of genetic origin?

Answer 41

In mosaicism, all cell lines arise from a single zygote and are genetically related, whereas in chimerism, the cell lines arise from two or more distinct zygotes and are not genetically related.

Question 42

How does mosaicism typically arise?

Answer 42

Mosaicism typically arises from a non-disjunction event that occurs after fertilisation (post-zygotically).

Question 43

How can chimerism occur either naturally or artificially?

Answer 43

It can occur naturally through twin-to-twin cell exchange in the womb or artificially through procedures like a bone marrow transplant.

Question 44

What is the 'maternal age effect' in the context of chromosomal abnormalities?

Answer 44

It is the observation that an increase in maternal age leads to an increased risk of meiotic non-disjunction, resulting in a higher risk of aneuploidies in egg cells.

Question 45

Define genomic imprinting.

Answer 45

It is the differential expression of maternally and paternally inherited alleles, where gene expression depends on the parent of origin.

Question 45

Why are women's oocytes particularly susceptible to the maternal age effect?

Answer 45

Oocytes are formed during foetal development and remain arrested in meiosis until ovulation, and this long period of arrest increases the risk of errors.

Question 46

Genomic imprinting is a normal epigenetic process primarily involving _____.

Answer 46

DNA methylation

Question 47

What happens to genomic imprints during gametogenesis?

Answer 47

During gametogenesis, the existing imprint is erased, and a new imprint is established according to the sex of the individual.

Question 48

What are the two main ways an imprinting disorder can be caused?

Answer 48

It can be caused by the deletion or mutation of the active allele, or by uniparental disomy (UPD).

Question 49

In an imprinting disorder, a mutation in which allele (the active or the silenced one) leads to a disease phenotype?

Answer 49

A mutation in the active allele leads to a disease phenotype.

Question 50

Angelman syndrome is an example of _____ imprinting, where the paternal allele is silenced.

Answer 50

paternal

Question 50

What is the most common cause of Angelman syndrome, accounting for 75% of cases?

Answer 50

A deletion of the maternal chromosome 15q11 region.

Question 51

Prader-Willi syndrome is an example of _____ imprinting, where the maternal allele is silenced.

Answer 51

maternal

Question 52

What is the most common cause of Prader-Willi syndrome, accounting for 70% of cases?

Answer 52

A deletion of the paternal chromosome 15q11 region.

Question 53

Define Uniparental Disomy (UPD).

Answer 53

A condition where both copies of a specific chromosome pair are derived from only one parent.

Question 54

Distinguish between heterodisomy and isodisomy.

Answer 54

Heterodisomy is inheriting both homologous chromosomes from one parent, while isodisomy is inheriting two copies of the same single chromosome from one parent.

Question 55

How does uniparental disomy cause Angelman syndrome?

Answer 55

It occurs when both copies of chromosome 15 are inherited from the father (paternal UPD), meaning there is no active maternal copy.

Question 56

How does uniparental disomy cause Prader-Willi syndrome?

Answer 56

It occurs when both copies of chromosome 15 are inherited from the mother (maternal UPD), meaning there is no active paternal copy.

Question 57

What percentage of Angelman syndrome cases are caused by paternal UPD of chromosome 15?

Answer 57

Approximately 5% of cases.

Question 58

What percentage of Prader-Willi syndrome cases are caused by maternal UPD of chromosome 15?

Answer 58

Approximately 25% of cases.