Lab 4 - Pathomechanisms of Genetic Disorders Flashcards
(42 cards)
Pleiotropy
describes genes that have multiple phenotypic effects/ genes that have more than one effect on the body. (Examples: Marfan syndrome, cystic fibrosis)
Genetic heterogeneity
production of the same or different phenotypes by different genetic mechanism.
Allelic heterogeneity
Describes conditions in which different alleles at a locus can produce variable expression of a disease. Depending on phenotype definition, allelic heterogeneity can cause two distinct diseases, as in Duchenne and Becker muscular dystrophy.
Locus heterogeneity
Describes diseases in which mutations at distinct loci can produce the same disease phenotype (examples: osteogenesis imperfecta; retinitis pigmentosa).
Expressivity
degree of expression of a gene in an individual/ the degree to which an allele expresses the phenotype.
Variable expressivity
A trait in which the same genotype can produce phenotypes of varying severity or expression. (example: neurofibromatosis type 1).
Penetrance
The probability of expressing a phenotype, given that an individual has inherited a predisposing genotype. If this probability is less than 1.0, the disease genotype is said to have reduced or incomplete penetrance.
Epistais
A gene interaction where one gene masks the phenotypic effect of another gene. Ex. Albinism
Polyphenism
The development of multiple, discrete phenotypes from a single genotype by organisms living in different environmental conditions
Monogenic
Describing a single-gene, or mendelian, trait
Digenic
interaction of two genes
Polygenic
Describes a trait caused by the combined additive effects of multiple genes.
Loss of heterozygosity
Describes a locus or loci at which a deletion or other process has converted the locus from heterozygosity to homozygosity or hemizygosity.
Semidominance (incomplete dominance)
Partial expression of each allele. The expression of each allele is different to that of each homozygous allele.
Semidominance in FH
heterozygous individuals are a ‘blending’ or midway point between the homozygous normal individuals (dd) and the homozygous individuals for the mutant allele (DD). The heterozygous (Dd) phenotype is more severe than the normal (dd) phenotype, but less severe than the phenotype seen in ‘DD’ individuals.
Familial hypercholesterolemia
- One of the most common autosomal dominant disorders.
- About 1/1,000,000 births is homozygous for the FH gene
- Most homozygotes experience MIs before 20 years of age, and an MI at 18 months of age has been reported. Without treatment, most FH homozygotes die before the age of 30 years
- FH is caused by a reduction in the number of functional LDL receptors on cell surfaces. Cellular cholesterol uptake is reduced, and circulating cholesterol levels increase.
- The number of effective receptors is reduced by about half in FH heterozygotes, and homozygotes have virtually no functional LDL receptors.
Genotypes of FH
dd
Dd
DD
Fenotypes
Healthy, no increased risk for MI
MI in middle age (40-50)
MI in childhood
Complete dominance
When the phenotype from one allele is always expressed and the phenotype of the second (recessive) allele is always hidden.
Complete dominance in Huntington’s disease
caused by a dominant allele.
You only need to inherit one copy of the faulty allele to have Huntington’s disease, unlike cystic fibrosis, where you need to inherit both copies. You can inherit Huntington’s disorder if one or both of your parents carry the faulty allele, because it is a dominant allele.
Huntington disease (HD) affects approximately 1 in 20,000 persons of European descent but is substantially less common in most other populations
interval between initial diagnosis to death is 15-20 y.
affected homozygotes appear to display a clinical course very similar to that of heterozygotes (in contrast to most dominant disorders, in which homozygotes are more severely affected).
Symtoms of Huntingston’s disease and age of onset
Symptoms develop between 30-50 y., characterized by a progressive loss of motor control, dementia and psychiatric disorders.
Difficulties in swallowing; aspiration pneumonia is the most common cause of death. Cardiorespiratory failure and subdural hematoma (due to head trauma) are other frequent causes of death.
The area most noticeably damaged is the corpus striatum
What kind of repeats causes HD?
CAG tandem repeats
Heterozygous inheritance of sickle cell anemia
If you are heterozygous, you have one allele for normal and one allele for the sickle hemoglobin, and produce both shapes of cells –> have sickle cell trait, but no sickle cell symptoms + cannot get malaria.
heterozygous carriers for sickle cell anemia are more resistant toward Plasmodium falciparum, the pathogen that causes tropical malaria. Infected erythrocytes rapid destroyed, and sickle shaped cells cannot carry oxygen –> parasite cannot survive
The ABO gene on which chromosome determines the blood groups of the ABO system?
chromosome 9q34
Which enzyme do allele A and allele B code for, and what is the function?
glycosyltransferase. Takes part in the glycosylation of proteins in the cell membrane.
