Genetics

Question 1

Give an outline of the scale of the human genome

Answer 1

• 3 billion base pairs
• 30,000 genes
• exome (exons) represents approximately 1–1.5% of the human genome

Question 2

What is the difference between balanced and unbalanced chromosomal rearrangement?

Answer 2

Balanced chromosome rearrangement

• All the chromosomal material is present

Unbalanced chromosome rearrangement

• Extra or missing chromosomal material, usually 1 or 3 copies of gene
• Causes major developmental problems

Question 3

Describe chromosome structure

Answer 3

Question 4

What is an Acrocentric Chromosome?

Answer 4

the centromere is not central and is instead located near the end of the chromosome

Question 5

Define Aneuploidy, Translocation, Insertions and deletions

Answer 5

Aneuploidy - whole extra or missing chromosome
-X chromosome aneuploidy better tolerated because of X chromosome inactivation

Translocation - rearrangement of chromosomes

Insertions and deletions -missing or duplicated material

Question 6

Define Robertsonian translocation

Answer 6

• Two acrocentric chromosomes stuck end to end
• Increased risk of trisomy(additional chromosome) in pregnancy

Question 7

Define Reciprocal translocation

Answer 7

• Two broken off chromosome pieces of non-homologous chromosomes are exchanged
• For most translocations, 50% of conceptions will have either normal chromosomes or the balandced translocation
• unbalanced products result in:
  
  • Miscarriage (large segments)
  • Dysmorphic delayed child (small segments)

Question 8

List Specific karyotypes

Answer 8

• 47XY +21 (trisomy 21) - Down’s syndrome
• 47 XY +14 (trisomy 14) - miscarriage
• 47 XY +18 - Edward syndrome, trisomy 18
• 45 X - Turner syndrome
• 47 XXY - Klinefelter syndrome

Question 9

Chromosome Microarray advantages and disadvantages

Answer 9

Array CGH- can detect any size of imbalance
-does not detect balanced rearrangements

Question 10

Define Somatic mosaicism

Answer 10

• Refers to the occurrence of two genetically distinct populations of cells within an individual, derived from a post-zygotic mutation
• May only affect a portion of the body
• Not transmitted to progeny
• Somatic mosaicism for a chromosomal abnormality could contribute to cancer
  
  • Changes could activate an oncogene or delete a tumour suppressor
• All cells suffer mutations as they divide
  
  • at meiosis and at mitosis
  • apprx 10^-6 per gee cell division
  • Repair mechanisms exists

Question 11

How to test whole chromosomes, DNA strands and bases?

Answer 11

whole chromosomes- Karyotype
(look at chromosomes)
DNA Strand- Microarray
(Quantifying segments of chromosome)
Single Bases- Sequencing
(analysing at the base level)

Question 12

What is the difference between PCR and Next Generation Sequencing?

Answer 12

PCR
-Allows us to select one small piece of the human genome from a patient (100 to 10,000 bases) and sequence it
-can only detect known sequences
NGS
- Sequence whole genome

Question 13

Describe missense, stop, insertion and deletion (in/out frame)

Answer 13

missense- singe base change, singe AA change
stop (nonesense)- premature stop codon
insertion- 1 base inserted, all AA after are diff
deletion- 1 base deleted, all AA after are diff. in frame still function.

Question 14

What does p. and c. mean ?

Answer 14

p. The change in the peptide (protein) sequence

c. The change in the mature mRNA sequence

Question 15

Give the 5 Variant Classifications

Answer 15

Class 1 Definitely benign
Class 2 Probably benign
Class 3 Unclassifiable
Class 4 Probably pathogenic
Class 5 Definitely pathogenic

Question 16

A genetic change may be due to…

Answer 16

• A disease causing mutation
• A polymorphism ( approx 3,000,000)
  (changes from the ‘normal’ sequence)
• A variant of unknown significance

Question 17

Define the term “Penetrance” in relation to effect of a genetic variation

Answer 17

The likelihood of having a disease
if you have a gene mutation

Question 18

6 Basic Symbols of Pedigree trees

Answer 18

Question 19

Give the key characteristics of Autosomal Dominant inheritance

Answer 19

• Only one copy required to cause disease, disease seen in all generations
• A person affected by an autosomal dominant disorder has a 50% chance of passing the mutated gene to each child
• Males and females equally likely to be affected

Question 20

Give the key characteristics of Autosomal Recessive inheritance

Answer 20

• 2 copies of faulty gene required to cause disease, often only 1 generation affected
• 1 in 4 risk of child being affected if parents are carriers
• Increased likelihood in consanguineous families

Question 21

Give the key characteristics of X-linked inheritance

Answer 21

• Gene fault lies on X chromosome
• Male with a single faulty allele will be fully affected but female carriers may only show mild features due to X- inactivation (around ½ of cells will have faulty gene)
  For a female carrier:
• Half of the male children will be affected
• Half of the female children will be carriers
  If an affected male has children:
• All of male children will be normal (no male to male transmission)
• All of female children will be carriers

Question 22

Mitochondrial inheritance

Answer 22

• Mitochondrial DNA is transmitted maternally, in the ovum
• The mitochondria in the cell have their own genome (single loop)
• a mutation in the mitochondrial genome may only be present in a proportion of the mitochondria