Genetic Terms Flashcards
Both alleles contribute to the phenotype of the heterzygote
Codominance
Examples- blood groups, alpha antitrypsin def, HLA groups
Patients with the same genotype have varying phenotypes
Variable expressivity
Ex: 2 patients with NF1 have differing severities of disease
Not all individuals with a mutant genotype show the mutant phenotype
Incomplete penetrate- % penetrance x probability of inheriting genotype= risk of expressing penetrance
Ex: BRCA1 genes don’t always result in breast or ovarian cancer
One gene contributes to multiple phenotypic effects
Pleiotropy
Ex: untreated PKU manifests with light skin, intellectual disability, and must body odor
Increased severity or earlier onset of disease in succeeding generations
Anticipation
Ex: Huntington’s disease with trinucleotide repeats
If a patient inherits or develops a mutation in a tumor suppressor gene, the complementary allele must be deleted/mutated before cancer develops. (Not true of oncogenes)
Loss of heterozygosity
Ex: Rb and two hit hypothesis, HNPCC, Li-Fraumeni syndrome
A heterozygous produces a nonfunctional altered protein that also prevents the normal gene product from functioning
Dominant negative mutation
Ex: mutation of a TF in its allosteric site. Non functioning mutant can still bind DNA, preventing wild type transcription factor from binding.
Tendency of certain alleles at 2 closely spaced loci to occur together more or less often than expected by chance. Measured in population, not in a family, and often varies in different populations
Linkage disequilibrium
Presence of genetically distinct cell lines in the same individual
Mosaicism
Somatic- mutations arises from mitotic errors after fertilization and propagates through multiple tissues or organs
Gonadal- mutation only in the egg or sperm cells. If parents and relatives do not have the disease, suspect germline mosaicism
Ex: McCune Albright syndrome- due to mutation affecting G protein signaling. Presents with cafe-au-last spots with ragged edges, polyostotic fibrous dysplasia, and one endocrinopathy. Lethal if mutation occurs before fertilization, but survivable in mosaicism.
Mutations at different loci can produce a similar phenotype
Locus heterogeneity
Ex: Albinism
Different mutations in same locus produces the same phenotype
Allergic heterogeneity
Ex: Beta thalassemia
Presence of both normal and mutated mtDNA, resulting in variable expression in mitochondrially inherited disease
Heteroplasmy
MtDNA passed from mother to all children
Offspring receives 2 copies of a chromosome from 1 parent and no copies from the other parent.
Uniparental disomy- euploid(correct # of chromosomes) so most can have normal phenotype
Heterodisomy (heterozygous) indicates a meiosis I error. Isodisomy (homozygous) indicates a meiosis II error or postzygotic chromosomal duplication of one of a pair of chromosomes, and loss of the other of the original pair.
Ex: UPD in an individual manifesting a recessive disorder when only one parent is a carrier- angel an or prader willi syndromes.
One gene copy is silenced by methylation, and only the other copy is expressed to get the parent of origin effects
Imprinting
PW syndrome- maternally imprinted (maternal genes are silenced) so disease occurs when PATERNAL allele is mutated/deleted. Chromosome 15 mutation on paternal allele or maternal uniparental disomy.
Angelman- paternal imprinted (paternal UBE3A gene is silenced) and disease occurs if MATERNAL allele is deleted or mutated. Chromosome 15 mutations on maternal allele or paternal uniparental disomy.
