Lecture 2: Genetic Disease

Question 1

Meiosis …. the chromosome number (… n), while Fertilization …. the chromosome number (… n)

Answer 1

Meiosis REDUCES the chromosome number (1 n), while Fertilization RESTORES the chromosome number (2 n)

Question 2

What is the difference between Polyploidy and Aneuploidy?

Answer 2

• Polyploidy is the change in chromosomal number such that every chromosome is affected (Ex. Triploidy; 3n= 69 Total Chromosomes, ;).
• Aneuploidy is the gain or loss of chromosomes where not all chromosomes are affected (Ex. Trisomy 21; 21+= 47 Total Chromosomes)

Question 3

True or False: Triploidy (3n) results in an early miscarriage due to the massive change to Gene Dosage

Answer 3

True; Triploidy results due to Error in Fertilization

- Foetus will have large head and small trunk due to intrauterine retardation and be inviable

Question 4

Aneuploidy is due to …. in either Meiosis 1 or 2

Answer 4

Aneuploidy is due to NON-DISJUNCTION in either Meiosis 1 or 2

Question 5

True or False: Aneuploidy typically occurs in Meiosis 2, but can still occur in Meiosis 1

Answer 5

False; Aneuploidy typically occurs in MEIOSIS 1, but can still occur in Meiosis 2

Question 6

What is the only viable monosomy?

Answer 6

Turner Syndrome (Female born with only 1 X Chromosome)

Question 7

The three viable trisomies are…

Answer 7

1) Patau Syndrome (13+)
2) Edward Syndrome (18+)
3) Down Syndrome (21+)
“PEDS”

Question 8

Aneuploidy risks (increase or decrease) with age and (increase/decrease) after having an aneuploid offspring

Answer 8

Aneuploid risks INCREASE with age (i.e. Old Egg Hypothesis) and INCREASE after having an aneuploid offspring

Question 9

What are some phenotype qualities associated with a Down Syndrome individual?

Answer 9

• Simian Palmar Crease
• Epicanthic Folds near eyes
• Mental Retardation
• Predisposition to Leukaemia and Early-Onset Alzheimers Disease (100% chance of development)

Question 10

What are the percentages of offspring genotypes (i.e. Normal, Trisomy and Monosomy) for a Non-Disjunction Event in Meiosis 1 and Meiosis 2?

Answer 10

ND in Meiosis 1 = 50% Monosomy, 50% Trisomy

ND in Meiosis 2= 25% Monosomy, 25% Trisomy and 50% Normal

Question 11

Is Non-Disjunction more likely to occur in the Female gamete (Egg) or Male gamete (Sperm)

Answer 11

Female gamete (Egg), especially in Meiosis 1 due to increase in Non-Disjunction potential

Question 12

In Robertsonian Translocations for Down Syndrome, what two chromosomes are translocated?

Answer 12

Chromosome 14 and 21 (Acrocentric stalks of Chromosome 21 break off and translocate to 14)

Question 13

Why is there a high reoccurrence of Robertsonian Translocations being passed to offspring?

Answer 13

Structural Rearrangement between Chromosomes 14 and 21 causes the two chromosomes not to be separated individually during Meiosis

Question 14

If the (Mother/Father) is the Robertsonian Translocation carrier, there is a greater risk of recurrence in the offspring

Answer 14

Mother

Question 15

Down Syndrome Mosaicism (i.e. some cell lines have 21+ and other cell lines are normal) occurs due to …..

Answer 15

Mitotic Non-Disjunction during Embryogenesis

Question 16

The region on Chromosome 21 where many of the genes associated with the Down Syndrome phenotype is called the …..

Answer 16

Down Syndrome Critical Region (DSCR)

Question 17

The …. gene on Chromosome …. creates ….. precursor protein which is associated with plaque formation in the Brain and ….. Disease.

Answer 17

The APP gene on Chromosome 21 creates BETA AMYLOID precursor protein which is associated with plaque formation in the Brain and ALZHEIMERS Disease.

Question 18

Down Syndrome Critical Region (DSCR) genes include ….

Answer 18

1) APP (Important one to know)
2) DYKR1A
3) DSCRI

2) and 3) important genes in signally pathways so just shows how a couple of genes can affect so many others and their protein products downstream

Question 19

…. Prenatal Screening use cell free Foetal DNA from Mother’s Blood to test for three copies of Chromosome 21

Answer 19

Non-Invasive Prenatal Screening (NIPS)

Question 20

True or False: Most Down Syndrome Diagnoses are from Second Trimester Screening

Answer 20

False; 85% of Down Syndrome diagnoses are from First Trimester Screening (i.e. Nuchal Translucency Thickness)

Question 21

What are some key details about Edward Syndrome?

Answer 21

• ND of Chromosome 18
• Rocker Bottom Heel
• More rare and severe than DS (90% mortality rate by 2 years)

Question 22

What are some key details about Patau Syndrome?

Answer 22

• ND of Chromosome 13
• Facial Malformations (ex. Cleft Palate) and Polydactyl
• Most rare and severe of the three trisomies (10% 1st year survival rate)

Question 23

Sex Chromosome Disorders are (More common/Less Common) and (More severe/Less severe) than Autosomal Chromosome Disorders.

Answer 23

Sex Chromosome Disorders are MORE COMMON and LESS SEVERE than Autosomal Chromosome Disorders.

Question 24

Sex Chromosome Disorders are tolerable due to …. of one of the X Chromosomes and the Y Chromosome having little genetic material.

Answer 24

Lyonisation of one of the X Chromosomes

Question 25

What is Lyonisation?

Answer 25

Process in which one X Chromosome in a female is randomly inactivated and turned into a Barr Body

• Maintains Gene Dosage
• Maternal or Paternal X is inactivated

Question 26

Would a male with Klinefelters Syndrome (XXY, 47) have a Barr Body

Answer 26

Yes, they would have 1 Barr Body

- Klinefelters Syndrome has the phenotype of being tall, female features and infertility

Question 27

What is the phenotype of a female with Turner Syndrome (X, 45)?

Answer 27

• Short neck, low posterior hairline and infertility
  Clinical features are due to Haploinsufficiency–> Need 2 copies of a gene to illicit proper function
  (Ex. SHOX gene on the X Chromosome requires 2 copies to promote long bone growth)

Question 28

Define Haploinsufficiency?

Answer 28

Haploinsufficiency occurs when only one copy of a gene is not enough to illicit proper gene function.
(Ex. SHOX gene on the X Chromosome requires 2 copies to properly promote long bone growth)