Basic Genetics

Question 1

What are the major Mendelian patterns of inheritance?

Answer 1

AD
AR
X-linked dominant
X-linked recessive

Question 2

What factors modify Mendelian patterns of inheritance?

Answer 2

Incomplete - Penetrance
Age related Penetrance
Variable expression
Genomic imprinting
Mitochondrial inheritance
De novo mutations

Question 3

What does mendelian mean?

Answer 3

Monogenic

Question 4

What does alleic heterogeneity mean?

What does locus heterogenetiy mean?

Answer 4

Alleic: different mutations in the same gene = leads to different phenotypes

Locus: mutations in different genes = same phenotype

Question 5

How do dominant mutations cause disease?

Answer 5

a) haploinsufficency = where the protein produced from one wild-type allele is not sufficient to sustain normal function

b) a dominant negative effect = where the mutated protein interferes with wild type protein and prevents normal functioning

Question 6

What is variable expression and what is genetic anticipation?

Answer 6

Variable expression refers to the different degrees of phenotype manifestation of a particular genotype

Genetic anticipation refers to the tendency of certain traits to INCREASE in severity through successive generation s

Question 7

What is incomplete penetrance?

Answer 7

Where not all individuals with the disease genotype manifest the condition (appears to skip a generation)

Question 8

What is the difference between type 1 and type 2 mosaicism?

Answer 8

Type 1: segmental affected skin has a heterzygous mutation, unaffected skin has no mutations

Type 2: skin is heterozygous, with segments of skin having a postzygotic mutation resulting in a ‘double hit’

Question 9

What is a polymorphism?

Answer 9

a non-pathogenic variant that has a population frequency of > 1 %

Question 10

What is a mutation (genetics?

Answer 10

a permanent change in the nucleotide sequence of DNA

• mis-sence
• non-sense
• silent
• frameshift

Question 11

What is the appropriate genetic test for a patient with multiple congential anomolies?

Answer 11

Chromosomal microarray

Question 12

What is the appropriate genetic test for a patient with a mendelian syndrome suspected

Answer 12

Targeted panel of genes

Question 13

What is the appropriate genetic test if the suspected gene is unknown?

Answer 13

Whole exome sequencing followed by whole genome sequencing

Question 14

What features should raise suspicion of a hereditary cancer syndrome?

Answer 14

Younger age
Multifocal tumours
multiple primary cancers
multiple affected family members
absence of environmental risk factors