Imprinting and Somatic Mutation Flashcards
Imprinting basics
Two parental genomes play complementary, non-identical roles
At an imprinted locus, only the maternal or paternal allele is expressed
Mechanism isn’t fully known, but DNA methylation is involved
When does imprinting occur?
Before fertilization
How does imprinting affect transcription?
Silences transcription
Is imprinting transmitted through mitosis in somatic cells?
Yes
When is imprinting reversible?
Gametogenesis: removed from parental DNA of opposite gender
Ex- allele that is maternally imprinted is removed in gametes of male offspring
How imprinting works in formation of offspring
Female: retains mother’s imprinted allele, reverses father’s imprinted allele
Male: retains father’s imprinted allele, reverses mother’s imprinted allele
Child receives one of two alleles from mother and one of two alleles from father
Imprinting and disease
Imprinting can cause problems when paired with mutations on non-imprinted parental allele: silencing of the normal allele causes disease allele to be the only one expressed in an individual
Prader-Willi syndrome and Angelman syndrome
Diseases associated with imprinting
Deletions at parental alelle for Prader-Willi and maternal allele for Angelman are expressed: other parent’s normal allele is silenced
Anticipation
Progressively earlier appearance and increased severity of a genetic disease in successive generations
Fragile X syndrome cause
Suppressed gene expression due to excessive DNA methylation in CGG repeats
Fragile X and anticipation
Families that have a history of fragile X tend to show an increased number of CGG repeats through generations: development of “premutation” (increased number of repeats, leading to more repeats in subsequent generations)
Too many repeats: abnormal methylation, unstable gene
Another disease that shows anticipation through increased number of methylated repeats
Huntington disease
Somatic mutations
Throughout the lifetime, somatic cells accumulate mutations
Most have no effects, but some can result in diseases like cancer
What can somatic mutations result in?
Genetic mosaicism: timing and cell of origin of a somatic mutation causes differential expression of mutation phenotype across body
Somatic mutations in neurodevelopmental disease
Arise in patient during development: affect multiple areas of body
May also arise later in development: just present in one organ (ex-brain)
Somatic mutations affect proliferation and migration of brain and other cells during development
