Inheritance patterns Flashcards
autosome
any chromosome, other than sex chromosomes, 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 - carriers
allelic heterogeneity
different mutations within the same gene result in the same clinical condition
individual with an autosomal recessive may be a compound heterozygote for 2 different mutations
autosomal recessive inheritance
disease manifest in homozygous state (double dose of affected allele)
typical features of autosomal recessive inheritance
males and females affected in equal proportions
affected individuals only in single generation
parents can be related
cystic fibrosis
commonest AR condition affecting northern europe
chronic condition affection mainly lungs and gut, variable presentation
incidence of cystic fibrosis
1 in 2500
gene affected by cystic fibrosis and mutations
CFTR gene on 7q31.2
over 1000 mutations (mutational hetergeneity)
commonest mutation in cystic fibrosis
deltaF508
standard cf carrier testing
detects top 29 mutations
diagnostic test for cf
sweat testing
genotype-phenotype correlations in cf
F508/F508 - pancreatic insufficiency and chronic lung disease
F508/R117H -majority are pancreatic sufficient but have chronic lung disease
consanguinity
reproductive union between 2 relatives
autozygosity
homozygosity by descent - inheritance of same altered allele through 2 branches of same family
autosomal dominant inheritance
disease manifest in the heterozygous state, i.e only one affected gene needed
typical features of autosomal dominant inheritance
males and females affected in equal proportions
affected individuals in multiple generations
transmission by individuals of both sexes to both sexes
penetrance
percentage of individuals with a specific genotype showing the expected phenotype
expressivity
range of phenotypes expressed by a specific genotype
recurrence risk
50% for transmission of mutation
depends on penetrance and expression
new mutation example
neurofibromatosis type 1 - up to 50% of cases occur due to de novo mutation
anticipation and example
genetic disorder affects successive generations earlier or more severely due to expansion of unstable triplet repeat sequences
myotonic dystrophy
somatic mosaicism
genetic fault present in only some body tissues
gonadal mosaicism
genetic fault present in gonadal tissue
late onset
condition not manifest at birth
hypertrophic cardiomyopathy
sex limited
condition inherited in AD pattern that seems to affect one sex more than the other
X linked inheritance
genes carried on X chromosome
typical features of X-linked inheritance
usually only males affected
transmitted through unaffected females
no male-to-male transmission
lyonization
generally only one of two X chromosomes active in each female cell
can be skewed
imprinting
epigenetic phenomenon causing genes to be expressed in a parent of origin specific manner
where is mitochondrial DNA inherited from?
mother
homoplasmy
eukaryotic cell whose copies of mitochondrial DNA are all identical (identically normal or identical mutations)
heteroplasmy
multiple copies of mtDNA in each cell
denote mutations affecting only a proportion of molecules in a cell
level varies between cells, organs and individuals
mitochondrial genetic disease
group of disorders caused by dysfunctional mitochondria
mutations in mtDNA, in nuclear genes or by acquisition e.g. drugs
