Definitions Flashcards
The differential expression of genetic material depending on whether it was inherited from the male or female parent.
IMPRINTING
If a gene is maternally imprinted, the maternally-derived allele is inactive and only the paternal allele is expressed. If, on the other hand, a gene is paternally imprinted, only the maternal allele is expressed. For imprinted genes, the sex of the parent transmitting the disorder is important, not the sex of the affected offspring
eg Angelman syndrome, Prader Willi, Hydatiform mole, Beckwith Wiedemann syndrome
The severity of some diseases increases as the disease is passed on through generations.
ANTICIPATION
Most commonly associated with expanded triplet-repeat mutations. The repeated sequence expands in successive generations, leading to a more abnormal phenotype.
eg Huntington’s disease, Fragile X, Spinocerebellar ataxia type 1, spinobulbar muscular atrophy
Heterogenous expression of a disease at the cellular or tissue level, resulting from cell-specific differences in the expression of a mutation or the presence of a chromosome aberration.
MOSAICISM
Error in mitosis after fertilization and the initiation of development (termed postzygotic mosaicism). As a consequence, the affected individual is mosaic, with some cells carrying the mutation, while others do not.
As an example, a mutation occurring at the eight-cell stage would (theoretically) lead to one of eight cells in the body carrying the mutation. The expression of disease phenotype will then depend on which cell types harbour the pathogenic mutation.
The proportion of persons carrying a pathogenic mutation who will manifest the disease, or the probability that a pathogenic mutation will result in disease.
PENETRANCE
A substitution that changes a codon for an amino acid to a stop codon, leading to premature termination of translation of the mRNA transcript and a truncated protein. But lecture says NOT a truncated protein.
NONSENSE MUTATION
A substitution that changes the codon for one amino acid to the codon for another amino acid. The composition and possibly the function of the protein does change.
MISSENSE MUTATION
A change in one base that results in no change in the amino acid sequence of the protein, due to the redundancy of the genetic code (there is more than one codon for most amino acids)
SILENT MUTATION
A substitution that alters binding affinities of transcript-related proteins, such as transcription factors, enhancers, silencers, or insulators. Such changes result in altered rates of transcription. Though protein structure is not altered by such noncoding variants, the level of transcript production can result in altered protein production, and in turn confer phenotypic variation.
REGULATORY POLYMORPHISM
Autosomal recessive disease that derives from a single parent- duplication of one parent’s chromosome, other parent’s chromosome is supressed so affected individuals are homozygous for chromosome from one parent
UNIPARENTAL DISOMY
Attachment of methyl groups to DNA at cysteine bases. Correlates with reduced transcription and is probably the principle mechanism in X chromosome inactivation and imprinting.
METHYLATION
Important in familial cancer genes eg BRCA1
IVF increases risk of…
Beckwith Wiedeman syndrome
Angelman syndrome
Mutations in different genes often cause the same disease
Locus heterogenicity
Different mutations in a gene can cause different diseases
Allelic heterogenicity
eg mutation in TRPV4 causes three different conditions: metatropic dysplasia, AD brachydactyly and arhtropathy, hered sensorimotor neuropathy IIc
The tendency for alleles of genes or genetic markers to be inherited in a non random fashion together
Linkage disequilibrium
Concept of where substitution of the third nucleotide in the codon is less likely to alter amino acid substitution than substitution of the first or second
Degeneracy of genetic code
How do you estimate carrier frequency?
Two times the square root of the incidence of disease
