inheritance patterns

Question 1

22q11 deletion syndrome

Answer 1

1 in 4-6,000

clinical features include: characteristic facial features, congenital heart disease, palatal abnormalities …

Question 2

Medel’s principles of genetics

Answer 2

segregation
dominance
independent assortment

Question 3

mendelian inheritance

Answer 3

autosomal vs. sex linked, dominant vs. recessive

Question 4

non-mendelian inheritance

Answer 4

imprinting, mitochondrial inheritance, multifactorial , mosaicism

Question 5

autosome

Answer 5

any chromosome, other than the sex chromosomes (X or Y), that occurs in pairs in diploid cells

Question 6

recessive

Answer 6

manifest only in homozygotes

Question 7

allele

Answer 7

one or more alternative forms of a gene at a given location (locus)

Question 8

homozygous

Answer 8

presence of identical alleles at a given locus, homozygotes are affected

Question 9

heterozygous

Answer 9

presence of two different alleles at a given locus, heterozygotes are unaffected and are usually referred to as carriers

Question 10

allelic heterogeneity

Answer 10

the situation where different mutations within the same gene result in the same clinical condition e.g. cystic fibrosis. Thus an individual with an autosomal recessive condition may be a compound heterozygote for two different mutations

Question 11

autosomal recessive inheritance

Answer 11

Disease manifest in the homozygous state
Typical features:
• male and females affected in equal proportions
• affected individuals only in a single generation
• parents can be related i.e. consanguineous

Question 12

cystic fibrosis

Answer 12

• most common AR condition affecting Northern European population
• chronic condition affecting mainly lungs and gut, variable presentation
• incidence of ≈ 1 in 2,500
• carrier frequency
• CFTR gene on 7q31.2
• Over 1,000 mutations (mutational heterogeneity)
• ∆F508 commonest mutation (approx. 80%)
• Standard carrier testing detects top 29 mutations (≈90%)
• Sweat testing remains diagnostic test (not genetic analysis)
• Neonatal screening programme for IRT (indirect marker)
Multiply risk of carrying of parents to work out risk of child

Question 13

Genotype – phenotype correlations in cystic fibrosis

Answer 13

• DF508/DF508 - pancreatic insufficiency and chronic lung disease
• DF508/R117H -majority are pancreatic sufficient but have chronic lung disease

Question 14

consanguinity

Answer 14

reproductive union between two relatives

Question 15

autozygosity

Answer 15

homozygosity by descent, i.e. inheritance of the same altered allele through two branches of the same family

Question 16

autosomal dominant inheritance

Answer 16

Disease manifest in the heterozygous state, i.e. only one affected gene needed
Typical features:
• Male and females affected in equal proportions
• Affected individuals in multiple generations
• Transmission by individuals of both sexes, to both sexes
• Penetrance & variability

Question 17

penetrance

Answer 17

the percentage of individuals with a specific genotype showing the expected phenotype

Question 18

expressivity

Answer 18

refers to the range of phenotypes expressed by a specific genotype

Question 19

recurrence risk

Answer 19

50% for transmission of mutation, BUT will the person be affected, depends on penetrance and expression

Question 20

new mutation

Answer 20

e.g. neurofibromatosis type 1, up to 50% of cases occur as a result of de novo mutation

Question 21

anticipation

Answer 21

whereby genetic disorder affects successive generations earlier or more severely, usually due to expansions of unstable triplet repeat sequence e.g. Myotonic Dystrophy

Question 22

somatic mosaicism

Answer 22

genetic fault present in only some tissues in body

Question 23

Gonadal (germline) mosaicism

Answer 23

genetic fault present in gonadal tissue

Question 24

late-onset

Answer 24

condition not manifest at birth (congenital), classically adult-onset. Example – Hypertrophic Cardiomyopathy

Question 25

sex-linked

Answer 25

condition inherited in AD pattern that seems to affect one sex more than another. E.g. BRCA1/2

Question 26

predictive testing

Answer 26

testing for a condition in a pre-symptomatic individual to predict their chance of developing condition

Question 27

x-linked inheritance

Answer 27

Genes carried on X chromosome 
Typical features:
•	Usually only males affected
•	Transmitted (usually) through unaffected females
•	No male-to-male transmission 
•	E.g. Haemophilia

Question 28

Lyonization (x inactivation)

Answer 28

generally only one of two X chromosomes active in each female cell. Can be skewed

Question 29

imprinting

Answer 29

genomic imprinting is an epigenetic phenomenon that causes genes to be expressed in a parent-of-origin-specific manner

Question 30

Homoplasmy

Answer 30

a eukaryotic cell whos copies of mitochondrial DNA are all identical (identically normal or have identical mutations)

Question 31

Heteroplasmy

Answer 31

there are multiple copies of mtDNA in each cell, the name given to denote mutations which affect only a proportion of the molecules in a cell, the level of heteroplasmy can vary between cells in the same tissue or organ, from organ to organ within the same person, and between individuals in the same family

Question 32

mitochondrial genetic disorders

Answer 32

• Group of disorders caused by dysfunctional mitochondria
• Caused by mutations in the mitochondrial DNA (15%)
• Caused by mutations in nuclear genes, whose gene products are imported into the mitochondria
• Acquired conditions caused by e.g. drugs

Question 33

example of multifactorial inheritance

Answer 33

cleft lip and palate