WEEK 9 (Translocations)

Question 1

Define Translocation

Answer 1

The movement of a chromosomal segment to a new location in the genome

Question 2

What happens in Reciprocal translocation?

Answer 2

Reciprocal translocation involves the exchange of segments between two non-homologous chromosomes -> It occurs when two non-homologous chromosome arms come close to each other so that exchange is facilitated -> If the exchange includes INTERNAL CHROMOSOME SEGMENTS, four breaks are required (two on each chromosome)

Question 3

What are the genetic consequences of reciprocal translocations?

Answer 3

Genetic information is not lost or gained only rearranged -> Translocation doesn’t directly alter the viability of individuals bearing it

Question 4

Describe Robertsonian translocation

Answer 4

There are breaks at the extreme ends of the SHORT ARMS of two non-homologous ACROCENTRIC CHROMOSOMES (centromere is not central and is instead located near the end of the chromosome) -> Small segments are LOST and larger segments FUSE at their centromeric region -> Produces a large SUBMETACENTRIC/METACENTRIC CHROMOSOME (centromere near the middle) called a ROBERTSONIAN TRANSLOCATION

Question 5

Robertsonian Translocation accounts for which disease?

Answer 5

Familial Down syndrome

[Down syndrome that is inherited, not due to non-disjunction]

Question 6

Robertsonian translocation commonly involves which chromosome pairs?

Answer 6

• 21
• 22
• 13
• 14
  -15

Question 7

What do balanced and unbalanced Robertsonian translocations result in?

Answer 7

• BALANCED TRANSLOCATIONS (no gain or loss of genetic material) = do not cause abnormal phenotype
• UNBALANCED TRANSLOCATIONS (missing or extra genes) = miscarriage, stillbirth and chromosomal imbalance (e.g Down syndrome, Patau syndrome)

Question 8

What are the main causes of Down syndrome?

Answer 8

• Meiotic non-disjunction (95%)
• Robertsonian Translocation (4%)
• Postfertilisation mitotic error (1%)

Question 9

__________________ is the most common viable chromosomal disorder and most common cause of genetic disability

Answer 9

Down syndrome

Question 10

What are the 5As of Down syndrome?

Answer 10

• Advanced maternal age
• Atresia
• Atrioventricular septal defect
• AML/ALL
• Alzheimer disease

Question 11

How is Down syndrome diagnosed?

Answer 11

The first trimester ultrasound commonly shows increased nuchal translucency and hypoplastic nasal bone

markers for Down syndrome are increased hCG and increased inhibin

Question 12

What are the Symptoms/Causes of Down syndrome?

Answer 12

• Intellectual disability
• A single line across the palm of the hand (palmar crease)
• Flat faces
• Almond-shaped eyes that slant up
• Hirschsprung disease
• Congenital heart disease
• Associated with early-onset of Alzheimer disease (chromosome 21 codes for amyloid precursor protein)

Question 13

What are Fragile sites?

Answer 13

Sites along the chromosome that appear to be susceptible to chromosome breakage

Question 14

_______________ is the most common form of inherited intellectual disability

Answer 14

Fragile X Syndrome

Question 15

Describe Fragile X Syndrome

Answer 15

An X-linked dominant inherited disorder which is caused by CGG trinucleotide repeats in FMR1 gene

SYMPTOMS:
- Severe intellectual disability
- Large prominent ears
- Large testes
- Elongated face (Large chin)