Genetics Flashcards
Both alleles contribute to the phenotype of the heterozygote
Codominance
Patients with the same genotype have varying phenotypes
Variable expressivity
Not all individuals with a mutant genotype show the mutant phenotype
Incomplete penetrance
One gene contributes to multiple phenotypic effects
Pleiotropy
Increased severity or earlier onset of disease in succeeding generations
Anticipation
If a patient inherits or develops a mutation in a tumor suppressor gene, the complementary allele must be delete/mutated before cancer develops. This is not true of oncogenes.
Loss of heterozygosity
Exerts a dominant effect. A heterozygote produces a nonfunctional altered protein that also prevents the normal gene product from functioning
Dominant negative mutation
Tendency for certain alleles at 2 linked loci to occur together more or less often than expected by chance. Measured in a population not in a family, and often varies in different populations
Linkage disequilibrium
Presence of genetically distinct cell links in the same individual
Mosaicism
Mutation arises from mitotic errors after fertilization and propagates through multiple tissues or organs. (Subtype of mosaicism)
Somatic mosaicisim
Mutation only in egg or sperm cells. If parents and relatives do not have the disease, suspect this (subtype of mosaicism)
Gonadal mosaicism
Mutations at different loci can produce a similar phenotype
Locus heterogeneity
Different mutations in the same locus produce the same phenotype
Allelic heterogeneity
Presence of both normal and mutated mtDNA, resulting in variable expression in mitochondrially inherited disease
Heteroplasmy
Offspring receives 2 copies of a chromosome from one parent and no copies from the other parent. 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.
Uniparental disomy
Hardy-Weinburg equation
p2 + 2pq + q2 = 1
Hardy-Weinburg Assumptions (4)
1) no mutation occurring at the locus
2) natural selection is not occurring
3) completely random mating
4) no net migration
Maternally derived genes are silenced (imprinted). Disease occurs when the paternal allele is deleted or mutated, although 25% of cases are due to maternal uniparental disomy.
Prader-Willi syndrome
Associated with a mutation or deletion of chromosome 15 of paternal origin. Results in hyperphagia, obesity, intellectual disability, hypogonadism, and hypotonia.
Prader-Willi Syndrome
Paternally derived UBE3A gene is silenced (imprinted).
Angelman Syndrome
Disease occurs when the maternal allele is delete or mutated. Results in inappropriate laughter (“happy puppet”), seizures, ataxia, and severe intellectual disability.
Angelman Syndrome
Inherited disorder resulting in increase phosphate wasting at proximal tubule. Results in rickets-like presentation. X-linked dominant
Hypophosphatemic rickets
Rare disorders, often presenting with myopathy, lactic acidosis, and CNS disease. Secondary failure in oxidative phosphorylation.
Mitochondrial myopathies
Cell death in optic nerve neurons, leads to subacute bilateral vision loss in teens/young adults, 90% males. Usually permanent
Leber hereditary optic neuropathy