Chromosomal Variations

Question 1

What is Aneuploidy and how does it arise?

Answer 1

It refers to the presence of an abnormal number of chromosomes in a cell and arises due to non-disjunction.

Question 2

What is non-disjunction?

Answer 2

It is the failure of chromosomes to segregate during cell division.

Question 3

Somatic aneuploidy is a feature of most cancers. Which cancers does trisomy 12 and trisomy 8 refer to?

Answer 3

Trisomy 12 = chronic Lymphocytic Leukemia (CLL).

Trisomy 8 = Acute Myeloid Leukemia (AML)

Question 4

What is monosomy and where is it most commonly seen?

Answer 4

It is the loss of a single chromsome. It occurs most commonly in the sex chromosomes of animals to equalise the expression of the genes (dosage compensation)

Question 5

What is 45, X also known as?

Answer 5

Turner Syndrome.

Question 6

When do the meiotic errors that most commonly give rise to Turner Syndrome occur?

Answer 6

They occur most commonly during spermatogenesis.

Question 7

Which three autosomal trisomies can still allow for a foetus to survive to birth and what syndromes do they give rise?

Answer 7

47, 13+ (Patau Syndrome).

47, 18+ (Edward Syndrome).

47, 21+ (Down’s Syndrome)

Question 8

What is trisomy?

Answer 8

The addition of an extra chromsome

Question 9

What is 47, XXY also known as?

Answer 9

Klinefelter Syndrome.

Question 10

What is 47, XYY also known as?

Answer 10

XYY syndrome.

Question 11

What is 47, XXX also known as?

Answer 11

Triple X syndrome.

Question 12

Why is non-disjunction more likely to occur during oogensis and with increasing maternal age? (3 reasons)

Answer 12

1) This is because meiosis in all eggs is arrested in meiosis I during synapsis of homologous chromosomes. It restarts at puberty but is arrested again in meiosis II and is not completed until fertilisation. As a result, each egg released has been arrested for a month longer than the previous one, which increases the likelihood of the event of non-disjunction in the egg.

Question 13

Other than meiotic arrest, why does the likelihood of non-disjunction increases with age?

Answer 13

There is the age-dependent decay of components of the meiotic machinery.

Question 14

What is the genetic constitution of Cri Du Chat Syndrome?

Answer 14

46, 5p-

Question 15

What is the genetic cause of Cri Du Chat Syndrome?

Answer 15

A variable deletion of the terminal portion of chromosome 5

Question 16

What does the Philadelphia chromsome refer?

Answer 16

it refers to the genetic abnormality present in chromsome 22 of patients with Chronic Myelogenous Leukaemia (CML).

Question 17

What gives rise to the Philadelphia chromsome?

Answer 17

A reciprocal translocation of genetic material between chromsome 9 and 22, which creates a fusion gene known as BCR-ABL-1.

Question 18

What is known as ‘Anticipation’?

Answer 18

It is the phenomena where the symptoms of a disease appear early with increased severity from generation to generation.

Question 19

Why does Anticipation occur?

Answer 19

It can occur due to presence of unstable repeats, which can undergo triplet expansion during meiosis.

Question 20

Where are the two locations of a gene, in which the presence of triplet repeat can give rise to disease, and why do how can they cause disease?

Answer 20

1) In untranslated regions. Their presence can interfere with expression, either by causing a loss of gene expression or causing a toxic RNA effect..
2) In exons as it can result in the production of an altered protein.

Question 21

What is the genetic cause of Fragile X syndrome?

Answer 21

A CGG repeat greater than 55 in the 5’UTR (untranslated region) on chromsome X, which leads to a loss of FMPR` protein function.

Question 22

What do CAG repeats encode for?

Answer 22

A polygutamine tract (polyQ)

Question 23

What is the genetic cause of Huntington’s

Answer 23

A CAG repeat greater than 36 in the N terminus of the Huntingtin gene.

Question 24

What causes Type 2 Diabetes and Myotonia in patients with Myotonic Dystrophy, respectively?

Answer 24

Alternative splicing of the insulin receptor causes Type 2 diabetes in DM patients.

Alternative splicing of the skeletal muscle chloride channel causes myotonia in DM patients.