inheritance patterns Flashcards
22q11 deletion syndrome
1 in 4-6,000
clinical features include: characteristic facial features, congenital heart disease, palatal abnormalities …
Medel’s principles of genetics
segregation
dominance
independent assortment
mendelian inheritance
autosomal vs. sex linked, dominant vs. recessive
non-mendelian inheritance
imprinting, mitochondrial inheritance, multifactorial , mosaicism
autosome
any chromosome, other than the sex chromosomes (X or Y), that occurs in pairs in diploid cells
recessive
manifest only in homozygotes
allele
one or more alternative forms of a gene at a given location (locus)
homozygous
presence of identical alleles at a given locus, homozygotes are affected
heterozygous
presence of two different alleles at a given locus, heterozygotes are unaffected and are usually referred to as carriers
allelic heterogeneity
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
autosomal recessive inheritance
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
cystic fibrosis
• 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
Genotype – phenotype correlations in cystic fibrosis
- DF508/DF508 - pancreatic insufficiency and chronic lung disease
- DF508/R117H -majority are pancreatic sufficient but have chronic lung disease
consanguinity
reproductive union between two relatives
autozygosity
homozygosity by descent, i.e. inheritance of the same altered allele through two branches of the same family
autosomal dominant inheritance
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
penetrance
the percentage of individuals with a specific genotype showing the expected phenotype
expressivity
refers to the range of phenotypes expressed by a specific genotype
recurrence risk
50% for transmission of mutation, BUT will the person be affected, depends on penetrance and expression
new mutation
e.g. neurofibromatosis type 1, up to 50% of cases occur as a result of de novo mutation
anticipation
whereby genetic disorder affects successive generations earlier or more severely, usually due to expansions of unstable triplet repeat sequence e.g. Myotonic Dystrophy
somatic mosaicism
genetic fault present in only some tissues in body
Gonadal (germline) mosaicism
genetic fault present in gonadal tissue
late-onset
condition not manifest at birth (congenital), classically adult-onset. Example – Hypertrophic Cardiomyopathy
