Biochemistry - Genetics Flashcards
What is codominance? Two examples?
Both alleles contribute to phenotype of the heterozygote. Examples: Blood groups A, B, AB; alpha 1 antitrypsin deficiency.
What is variable expressivity? One example?
Phenotypes varies among individuals with same genotype. Neurofibromatosis type 1 (NF1) shows varying severity of disease between individuals.
What is incomplete penetrance? One example?
Not all individuals with a mutant genotype shows the mutant phenotype. BRCA1 does not always result in breast or ovarian cancer.
What is pleiotropy? One example?
One gene contributes to multiple phenotypic effects. Eg, Untreated phenylketonuria (PKU) manifests with light skin, intellectual disability, and musty body odor.
What is anticipation? Example?
Increased severity or earlier onset of disease in succeeding generations. Trinucleotide repeat diseases, eg. Huntington’s.
What is loss of heterozygosity, and the classic example?
The two hit hypothesis; if patient inherits a tumor suppressor gene defect, the complementary gene must be mutated before cancer develops. Eg, loss of function. Retinoblastoma.
What is a dominant negative mutation?
When a heterozygote has a nonfunctional altered protein that also prevents the normal gene from functioning. Eg, ineffective transcription factor that binds to allosteric site, thereby preventing regular transcription factor from binding.
What is linkage disequilibrium?
Tendency for certain alleles at 2 linked loci to occur together more of less often than expected by chance. Measured in population, not family, often varies.
What is mosaicism? Two different kinds of mosaicism?
Presence of genetically distinct cell lines in the same individual. Somatic mosaicism: mutation arises from mitotic errors after fertilization and propagates through multiple tissues or organs. Gonadal mosaicism: mutation only in egg or sperm cells. McCune-Albright syndrome is an example of somatic mosaicism.
Locus heterogeneity?
Mutations at different loci can produce a similar phenotype. Albinism.
Allelic heterogeneity?
Different mutations in the same locus produce the same phenotype. Eg, B-thalassemia.
What is heteroplasmy?
Presence of both normal and mutated mtDNA, resulting in variable expression in mitochondrially inherited disease.
What is uniparental disomy? Where is the error in heterodisomy vs isodisomy?
Offspring receives 2 copies of a chromosome from 1 parent and no copies from the other parent. Heterodisomy: meiosis I error. Isodisomy: Meiosis II error.
What are the assumptions for the Hardy-Weinberg law?
No mutation occuring at the locus. Natural selection is not occuring. Completely random mating. No net migration.
What are the Hardy Weinberg equations?
p squared + 2pq + q squared = 1 and p + q = 1, in which p and q are the frequencies of separate alleles. P2 is frequency of homozyg for allele p, 2pq = frequency of heterozygotes, and q2 = freq of homoz for allele q.
What is imprinting? Classic example.
At some loci, only one allele is active, the other is inactive (methylation!). With one allele inactivated (“imprinted”), mutation in the active allele = disease. Prader-Willi vs. Angelman’s = both mutation in Ch 15.
What is Prader-Willi syndrome?
Paternal gene on Ch 15 is deleted/mutated, mom gene usually imprinted. Sx: hyperphagia, obesity, intellectual disability, hypogonadism, hypotonia.
What is angelMan’s syndrome
Maternal gene on Ch 15 is deleted/mutated, dad gene usually imprinted. Sx: inappropriate laughter (happy puppet), seizures, ataxia, and severe intellectual disability.
What is the inheritance pattern and defect in ADPKD?
AD. Mutation in PKD1 (Ch. 16) - 85%, or PKD2 (Ch 4) leads to bilateral massive enlargement of kidneys due to multiple large cysts. Also associated with cysts in liver and berry aneurysm.
What is the inheritance pattern and defect in Familial adenomatous polyposis?
AD. Mutation on Chromosome 5q (APC gene). Colon becomes covered with adenomatous polyps after puberty. 100% progression to colon cancer unless colon resected.
