Lecture 1: Chromosomal Abnormalities

Question 1

What are the three main categories of Genetic Disease?

Answer 1

1) Chromosomal Abnormalities
2) Single Gene (Mendelian) Disorders
3) Complex Multifactorial Disorders

Question 2

True or False: Younger women have an increased prevalence of having offspring with chromosomal abnormalities?

Answer 2

False: Older women have an increased prevalence of having offspring with chromosomal abnormalities = Old Egg Hypothesis

Question 3

What is a chromosome?

Answer 3

• Organized structure of DNA and associated folding proteins

- Composed of a singular piece of DNA and its associated genes

Question 4

True or False: The q arm is longer than the p arm?

Answer 4

True: The q arm is longer than the p arm

Question 5

Cytogenetics is the study of the ….

Answer 5

Chromosome

Question 6

The three types of Chromosomes are…

Answer 6

1) Metacentric
2) Submetacentric
3) Acrocentric

Question 7

Chromosomes 14 and 21 are examples of which type of Chromosome?

Answer 7

Acrocentric Chromosomes (i.e. Robertsonian Translocations may occur between 14 and 21)

Question 8

What part of the Acrocentric Chromosome can break off and lead to chromosomal abnormalities?

Answer 8

The Stalks of the Acrocentric Chromosome

Question 9

The two types of Chromosomal Abnormalities are…

Answer 9

1) Numerical: Due to improper fertilization/cell division (Mitosis or Meiosis)
2) Structural: Due to breakage of the Chromosome

Question 10

The four major types of Structural Chromosomal Rearrangements are…

Answer 10

1) Duplications
2) Insertions/Deletions
3) Inversions
4) Translocations

Question 11

In …. Inversion the Centromere IS affected, whereas in …. Inversion the Centromere is NOT affected.

Answer 11

In PERICENTRIC Inversion the Centromere IS affected, whereas in PARACENTRIC Inversion the Centromere is NOT affected.

Question 12

What chromosomal deletions occur for the following:
A) Cri-Du Chat Syndrome
B) Wolf Hirschhorn Syndrome
C) Di George Syndrome

Answer 12

A) Cri-Du Chat= p arm Deletion of Chromosome 5 (5p-)
B) Wolf Hirschhorn= p arm Deletion of Chromosome 4 (4p-)
C) Di George= q arm Deletion of Chromosome 22 (22q-)

Question 13

True or False: You would be able to see the Di George Deletion on a standard Karyotype?

Answer 13

False: Di George Syndrome is a Micro-deletion (22q-)

- Requires FISH probing to be detected

Question 14

If a child has wide-dropped eyes, mental retardation and/or a cat-like cry, what Chromosomal Abnormality might they have?

Answer 14

Deletion in the p arm of Chromosome 5 (Cri-Du-Chat Syndrome)

Question 15

Chromosomal Abnormalities affect ….. Dosage?

Answer 15

Gene

Question 16

Individuals with Di George Syndrome have an increased risk of developing 1) ….. and 2) …..

Answer 16

1) ADHD and 2) Schizophrenia

- 1/4 Adults with Di George Syndrome may develop Schizophrenia

Question 17

True or False: All Copy Number Variations (CNVs) of genes are Pathogenic?

Answer 17

False: Cytogenetics has shown some genes that have been duplicated/deleted are not pathogenic
- Copy Number Variation (CNV) is normal in healthy individuals

Question 18

Exchange of genetic material between Non-Homologous Chromosomes is ….

Answer 18

Reciprocal Translocation

Question 19

Robertsonian Translocations occur between …. Chromosomes due to the stalks breaking off and forming sticky ends

Answer 19

Acrocentric, Non-Homolgous

Question 20

A Reciprocal Translocation of Chromosomes 9 and 22 forms a ….. Chromosome

Answer 20

Philadelphia (Go Birds!)

Question 21

True or False: Individuals with a Philadelphia Chromosome are at higher risk of certain types of Leukemias

Answer 21

True (Ex. Philadelphia Chromosome Positive (+) Acute Lymphoblastic Leukaemia: Due to the aberrant Bcr-Abl gene fusion constitutively activating Tyrosine Kinase, leading to excess cell proliferation)

Question 22

True or False: Robertsonian 14-21 Translocations have a phenotype similar to Down Syndrome individuals

Answer 22

False; Individuals with a 14-21 Robertsonian Translocation have a normal phenotype