- Codominance
- Both alleles for a trait are fully and simultaneously expressed in the phenotype of a heterozygote.
- Classic Ex: ABO blood group system, where a person with the AB genotype expresses both A and B antigens.
- Variable Expressivity
- Individuals with the same disease-causing genotype exhibit a range of signs and symptoms.
- Classic Ex: Neurofibromatosis type 1 (NF1), where patients can have anything from a few café-au-lait spots to severe complications like neurofibromas and optic gliomas.
- Incomplete Penetrance
- Not all individuals with a pathogenic genotype will show any signs or symptoms of the disease. Said to “skip” a generation.
- Classic Ex: Many hereditary cancer syndromes like those caused by BRCA1/2 mutations, where carrying the gene increases the risk of cancer but doesn’t guarantee it.
- Pleiotropy
- A single gene influences multiple, often seemingly unrelated, phenotypic traits.
- Classic Ex: Phenylketonuria (PKU), where a single gene defect leads to intellectual disability, light skin, and a musty body odor.
- Anticipation
- A genetic disorder is passed to the next generation and the symptoms become apparent at an earlier age, or with increased severity.
- Classic Ex: Trinucleotide repeat expansion disorders like Huntington’s disease, myotonic dystrophy, and Fragile X syndrome.
- Loss of Heterozygosity (LOH)
- In a cell that has one mutated and one normal allele of a tumor suppressor gene, the loss of the remaining normal allele leads to cancer development. This is also known as the “two-hit hypothesis”.
- Classic Ex: Retinoblastoma (Rb), where an individual may inherit one mutated RB1 allele and a second “hit” (somatic mutation) in a retinal cell leads to tumor formation.
- Epistasis
- The effect of one gene is modified by one or several other genes (which are sometimes called modifier genes). The gene whose phenotype is expressed is said to be epistatic, while the gene whose phenotype is altered or suppressed is said to be hypostatic.
- Aneuploidy
- The presence of an abnormal number of chromosomes in a cell, such as having 45 or 47 chromosomes instead of the usual 46.
- Classic Ex: Trisomy 21 (Down syndrome), Trisomy 18 (Edwards syndrome), Trisomy 13 (Patau syndrome).
- Dominant Negative Mutation
- A mutation where the altered gene product not only is nonfunctional but also inhibits the function of the normal protein produced by the wild-type allele in a heterozygote.
- Classic Ex: A mutation in a transcription factor that prevents the normal transcription factor from binding to DNA.
- Linkage Disequilibrium
- The non-random association of alleles at two or more loci in a population. Essentially, certain alleles are inherited together more or less often than would be expected by chance.
- Mosaicism
- The presence of two or more cell lines with different genotypes in a single individual, which arose from a single fertilized egg.
- Somatic mosaicism: Mutation arises after fertilization and affects a subset of body cells; cannot be passed to offspring.
- Gonadal (germline) mosaicism: Mutation is confined to the egg or sperm cells. The parent is unaffected but can pass the mutation to offspring.
- Locus Heterogeneity
- The same disease or phenotype can be caused by mutations in genes at different chromosomal loci.
- Classic Ex: Albinism, which can be caused by mutations in several different genes involved in melanin production.
- Allelic Heterogeneity
- Different mutations at the same locus (i.e., in the same gene) can produce the same phenotype.
- Classic Ex: Cystic fibrosis, where numerous different mutations in the CFTR gene can all result in the disease.
- Heteroplasmy
- The presence of both normal and mutated mitochondrial DNA (mtDNA) within a single cell. This results in variable expression of mitochondrial inherited diseases.
- Uniparental Disomy (UPD)
- An individual receives two copies of a chromosome from one parent and no copies from the other.
- Can lead to disease if it involves an imprinted gene or if it unmasks a recessive disorder.
- Classic Ex: Prader-Willi and Angelman syndromes can result from UPD of chromosome 15.