Biochemistry-Genetics Flashcards
What is codominance?
both alleles contribute to the phenotype of the heterozygote (e.g. blood groups A, B, AB)
What is variable expressivity?
phenotype varies among individuals with the same genotype (2 pts. with neurofibromatosis type I (NF1) may have varying disease severity)
What is incomplete penetrance?
not all individuals with a mutant genotype show the mutant phenotype (e.g. BRCA gene mutations do not always result in breast or ovarian cancer)
What is pleiotropy?
when one gene contributes to multiple phenotypic effects (e.g. untreated PKU manifests with light skin, intellectual disability, and musty body odor)
What is anticipation?
increased severity or earlier onset of disease in succeeding generation (.e.g Huntington disease)
Describe loss of heterozygosity
if a pt inherits or develops a mutation in a tumor supressor gene, the complementary allele must be deleted/mutated before cancer develops. THis is not true of oncogenes (i.e. two hit theory)
What are dominant negative mutations?
exerts a dominant effect. A heterozygote produces a nonfunctional altered protein that also prevents the normal gnee product from functioning
What is linkage disequilibrium?
tendency for certain alleles at 2 linked loci to occur together more or less often than expected by change. Measured in a population, not in a family, and often varies in different populations
What is heteroplasmy?
presence of both normal and mutated mtDNA, resulting in variable expression in mitochondrially inherited disease
What is allelic heterogeneity?
different mutations in the same locus produce the same phenotype (i.e. B-thalassemia)
What is locus heterogeneity?
different mutations in the same locus produce the same phenotype (i.e. albinism)
What is mosaicism?
presence of genetically distinct cell lines in the same individual
Somatic mosaicism- mutation arises from mitotic errors after fertilization and prpagates through mutliple tissues or organs
Gonadal mosaicism- mutation only in egg or sperm cells
What is McCune-Albright Syndrome?
due to mutations affecting G-protein signaling. Presents with unilatera cafe-au-lait spots, polyostotic fibrous dysplasia, precocious puberty, and multiple endocrine abnormalities
lethal if mutation occurs before fertilization (affecting all cells), but survivable in pts with mosaicism
What is uniparental disomy?
When an offspring receives 2 copies of a chromosome from 1 parent and no copies from the other parent.
Heterodisomy (heterozygote) indicates a meiosis I error
Isodisomy (homozygous) indicates a meiosis II error or postzygotic chromosomal duplication of one of a pair of chromosomes, and the loss of the other of the original pair
Example of uniparental disomy
Uniparental is eUploid (correct number of chromosomes), not aneuploid. Most occurences of UPD leads to normal phenotypes. Consider UDP in an individual manifesting in a recessive disorder when only one parent is a carrier
If a population is in Hardy-Weinberg equilbrium and if p and q are the frequencies of seperate alleles, then: p2 + 2pq + q2= 1 and p+q=1 which implies that:
p2= frequency of homozygosity for allele p
q2= frequency of homozygosity for allele q
2qp= frequency of heteroxygote
In Hardy-Weinberg equilbrium, the frequency of an X-linked recessive disease in males=
q, and in females = q2
Hardy- Weinberg law assumptions:
No mutation occuring at the locus
Natural selecction is occurring
Completely random mating
No net migration
What is imprinting?
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 causes disease
E.g. both Prader-Willi and Angelman syndromes are due to mutation or deletion of genes on chromosome 15
What is Prader Willi syndrome?
maternal imprinting disease where the gene from mom is normally silent and the paternal gene is deleted/mutated resulting in:
hyperphagia, obesity, intellectual disability, hypogonadism, and hypotonia
25% of Prader Willi syndrome cases are due to what?
maternal uniparental disomy (two maternally imprinted genes are recieved; no paternal genes received)
What is Angelman syndrome?
paternal imprinting disease when the gene from dad is normally silent and the maternal gene is deleted/mutated resulting in:
inappropriate laughter (“happy puppet”)
seizures
ataxia
and severe intellectual disability
What inheritance pattern is shown below?
AD- often due to defects in structural genes; often pleiotropic (multiple apparently unrelated effects) and variably expressed
AR recessive pattern
Often due to enzymes deficiencies (usually seen in only 1 generation and skips); commonly more severe than dominant disorders and pts often present in childhood
Increased risk in consanguineous families
