Biochem - Genetics (Genetic terms, Hardy-Weinberg, & Imprinting) Flashcards
Pg. 84-85 in First Aid 2014 Sections include: -Genetic terms -Hardy-Weinberg population genetics -Imprinting
What is the definition of codominance? Give 2 examples.
Both alleles contribute to the phenotype of the heterozygote; (1) Blood groups A, B, AB (2) alpha1-antitrypsin
What is the definition of variable expressivity? Give an example.
Phenotype varies among individuals with same genotype; 2 patients with neurofibromatosis type I (NF1) may have varying disease severity
What is the definition of incomplete penetrance? Give an example.
Not all individuals with a mutant genotype show the mutant phenotype; BRCA1 gene mutations do not always result in breast or ovarian cancer
What is the definition of pleiotropy? Give an example.
One gene contributes to multiple phenotypic effects; Untreated phenylketonuria (PKU) manifests with light skin, intellectual disability, and musty body odor
What is the definition of anticipation? Give an example.
Increased severity or earlier onset of disease in succeeding generations; Trinucleotide repeat diseases (e.g., Huntington disease)
Define loss of heterozygosity. To which genes does it apply versus does not apply? Give an example.
If a patient inherits or develops a mutation in a tumor suppressor gene, the complementary allele must be deleted/mutated before cancer develops. This not true of oncogenes; Retinoblastoma and the “two-hit hypothesis”
What is the definition of dominant negative mutation? Give an example.
Exerts a dominant effect. A heterozygotes produce a nonfunctional altered protein that also prevents the normal gene product from functioning; Mutation of a transcription factor in its allosteric site. Nonfunctioning mutant can still bind DNA, preventing wild-type transcription factor from binding
What is the definition of linkage disequilibrium? In what context is it measured, and by what does it often vary?
Tendency for certain alleles at 2 linked loci to occur together more often than expected by chance; Measured in a population, not in a family, and often varies in different populations
What is the definition of mosaicism? From what does it arise?
Presence of genetically distinct cell lines in the same individual; Arises form mitotic errors after fertilization;
What are the types of mosaicism? How does the mutation occur in each?
Somatic mosaicism - mutation propagates through multiple tissues or organs; Gonadal mosaicism - mutation only in egg or sperm cells
What clinical condition exemplifies mosaicism? How does it differ in somatic versus gonadal types?
McCune-Albright syndrome is lethal if the mutation is somatic, but survivable if gonadal
What is the definition of locus heterogeneity? Give an example.
Mutations at different loci can produce a similar phenotype; Albinism
What is the definition of allelic heterogeneity? Give an example.
Different mutations in the same locus produce the same phenotype; Beta-thalassemia
What is the definition of heteroplasmy?
Presence of both normal and mutated mtDNA, resulting in variable expression in mitochondrial inherited disease
What is the definition of uniparental disomy?
Offspring receives 2 copies of a chromosome from 1 parent and no copies from the other parent
What are the types of uniparental disomy, and what kind of error is indicated by each?
(1) Heterodisomy (heterozygous) indicates a meiosis I error (2) 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
What ploidy results from uniparental disomy?
Uniparental is eUploid (correct number of chromosomes), not aneuploid
What kind of phenotype typically results from UPD?
Most occurrences of UPD –> normal phenotype
In what clinical context should UPD be considered?
Consider UPD in an individual manifesting a recessive disorder when only one parent is a carrier
What are the 4 assumptions made in the Hardy-Weinberg law?
Hardy-Weinberg law assumptions include: (1) No mutation occurring at the locus (2) Natural selection is not occurring (3) Completely random mating (4) No net migration
Give and define the equations that apply if a population is in Hardy-Weinberg equilibrium.
If a population is in Hardy-Weinberg equilibrium and if p and q are frequencies of separate alleles, then: p^2 + 2pq + q^2 = 1 and p + q = 1, which implies that: p^2 = frequency of homozygosity for allele p, q^2 = frequency of homozygosity for allele q, 2pq = frequency of heterozygosity (carrier frequency, if an autosomal recessive disease)
According Hardy-Weinberg equilibrium, what is the frequency of an X-linked recessive disease in males versus females?
The frequency of an X-linked recessive disease in males = q and in females = q^2
Draw a Punnett Square using Hardy-Weinberg equations.
See p. 85 in First Aid 2014 for visual
What is imprinting? How does this lead to disease?
At some loci, only one allele is active; the other is inactive (imprinted/inactivated by methylation). With one allele inactivated, deletion of the active allele –> disease.
What mutation causes both Prader-Willi and Angelmann syndromes? What genetic term can also cause such imprinting?
Both Prader-Willi and Angelmann syndromes are due to mutation or deletion of genes on chromosome 15; Can also occur as a result of uniparental disomy
What defines Prader-Willi syndrome?
Maternal imprinting: gene from mom is normally silent and Paternal gene is deleted/mutated; Think: “ P for Prader & Paternal”
What are 5 characteristics in the presentation of Prader-Willi syndrome?
Results in (1) hyperphagia (2) obesity (3) intellectual disability (4) hypogonadism (5) hypotonia
What defines Angelman syndrome?
Paternal imprinting: gene from dad is normally silent and Maternal gene is deleted/mutated; Think: “M for angelMan & Maternal”
What are 4 characteristics in the presentation of Angelman syndrome?
Results in (1) inappropriate laughter (“happy puppet”) (2) seizures (3) ataxia (4) severe intellectual disability.
What percentage of Prader-Willi syndrome cases are due to maternal uniparental disomy? What does this mean?
25% of cases due to maternal uniparental disomy (two maternally imprinted genes are received; no paternal gene received)
What percentage of Angelman syndrome cases are due to paternal uniparental disomy? What does this mean?
5% of cases due to parental uniparental disomy (two paternally imprinted genes are received; no maternal gene received)
