Clinical Genetics 1

Question 1

Size of targeted regions in assays

Answer 1

Genome – 127 volumes
Exome – 2.5 volumes
500 gene panel – 40 pages
50 gene panel – 4 pages
Single gene – <1/10 of a page

Question 2

Limit of detection - % allele burden

Answer 2

Assay type Average limit of detection
(% allele burden)
Genome sequencing ~20 – 30%
Exome sequencing ~20 – 30%
NGS-based gene panels 5 – 10%
Sanger sequencing 20%
Single mutation assay <10%

Question 3

Some mutation types are difficult to detect by genome or exome sequencing technologies

Answer 3

Mutation types:

Single nucleotide variant
Small indels (<10-20 bp)
Copy-number variants
Structural variants
Larger indels

Question 4

Autosomal Dominant

Answer 4

• An affected person usually has at least one affected parent
• Affects both genders
• Transmitted by both genders
• A child born from an affected x unaffected mating has a 50% chance of being affected

Example: Huntington’s disease

Question 5

Autosomal Recessive

Answer 5

• An affected person usually has unaffected parents
• Parents of affected person are usually aymptomatic carriers
• Affectes both genders
• After one affected child, each subsequent child has a 25%
  chance of being affected
  Example: Cystic Fibrosis, sickle-cell anemia etc

Question 6

Sex Linked
(X-linked recessive)

Answer 6

• Affects mainly males
• An affected person usually has unaffected parents
• Mother of affected persons are usually asymptomatic
  carriers and may have male relatives
• Females are rarely affected
• There is no male-to-male transmission but in some cases
  (affected male x carrier female) – it might appear to be the
  case

Examples: Haemophilia, red-green colour blindness etc

Question 7

Sex Linked
(X-linked dominant)

Answer 7

• Affects both genders but more females affected
• Females show more variable phenotype
• The child of an affected female has 50% chance of being affected
• For an affected male, none of his son but all of his daughters are affected

Example: Rett Syndrome, Incontinentia Pigmenti etc

Question 8

Sex Linked
(Y-linked)

Answer 8

• Affects only males
• All affected male has an affected father
• All son of an affected father are affected
• No daughter (and their children) of an
  affected male will be affected

Example: Usually diseases linked to Male infertility or male specific phenotypes. But not proven

Question 9

Genetic Diseases: examples
(chromosomal abnormalities)

Answer 9

Down’s Syndrome (Trisomy 21, human)
Patau Syndrome (Trisomy 13)
Edwards Syndrome (Trisomy 18)