PCOL 838 Exam 1
gene - ANS-a segment of dna that encodes a pdt responsible for a measurable trait
locus - ANS-location of a gene on a chromosome
allele - ANS-a variant form of a gene
mutation - ANS-a biochemical event such as a nucleotide change, deletion, or insertion
that has produced a new allele.
heterozygosity - ANS-Having two alleles at the same locus that are diff erent.
Hemizygosity - ANS-A term referring to the presence of only one allele at a locus, either
because the other allele is deleted or because it is normally not present, e.g., X-linked
genes in males.
polymorphism - ANS-an allele present in 1% or more of a population;
phenotype - ANS-any characteristic that can be measured, with the type of
measurement depending on the characteristic.
how can 2 individuals w/ the same mutation have the different severity of disease -
ANS-penetrance: manifestation of disease phenotype under a set of predefined criteria
(% of people who inherit mutation and express associated trait)
Incomplete penetrance of dominantly inherited disease- why deleterious allele persist in
population
- Same mutation can affect different tissues-> different phenotype-> variable
expressivity
Explain the pathophysiologic difference between
mutations that act via loss of function and those that
act via dominant negative gene action - ANS-
Recessive loss of function mutation - ANS-autosomal, classical Mendelian inheritance,
only one allele is working, gives rise to only 50% protein level, need both alleles to
manifest disease phenotype-> recessive inheritance
, Dominant loss of function mutation - ANS-50% protein level= not enough for normal
function->dominance inheritance. most are semidominant w both loss of function alleles
manifesting more severe phenotype
Dominant Negative Gene action - ANS-Involved in genes encoding proteins involved in
oligomeric or polymeric protein complexes
Mutant protein disrupts the formation of normal
protein complexes->inhibiting normal function=dominant inheritance
What are the different mode of inheritance - ANS-- depending on locus of mutated
gene. Autosomal vs X-linked. Autosomal recessive or Dominant. X- linked dominant
fragile X syndrome) or recessive (hemophilia) mostly manifests in men bec of
hemizygosity. Codominance. Maternal inheritance or matroclinous inheritance in
mitochondria.
Leber hereditary optic neuropathy
(LHON - ANS-Mutations in genes located in the mitochondria DNA.
•
Lead to optic cell death and progressive vision loss.
•
Incomplete penetrance: 50% of male and 85% of
female never experience any vision loss of related
health problems.
•
Affected individuals are typically homoplasmy,
heteroplasmy individual will eventually become
homoplasmy
factors that can cause DNA mutation - ANS-- cellular/ metabolism
- UV light exposure
- Ionizing radiation
-chemical exposure
- replication errors (tautomeric shift)
when dna damage is sensed by the cells - ANS-- cellcycle checkpoint axtivation
- transcriptional program activation
- DNA Repair: direct reversal, base excision repair, nucleotide excision repair, mismatch
repair, double stranded break repair (non-homologous end joining or homologous
recombination)
-Apoptosis
gene - ANS-a segment of dna that encodes a pdt responsible for a measurable trait
locus - ANS-location of a gene on a chromosome
allele - ANS-a variant form of a gene
mutation - ANS-a biochemical event such as a nucleotide change, deletion, or insertion
that has produced a new allele.
heterozygosity - ANS-Having two alleles at the same locus that are diff erent.
Hemizygosity - ANS-A term referring to the presence of only one allele at a locus, either
because the other allele is deleted or because it is normally not present, e.g., X-linked
genes in males.
polymorphism - ANS-an allele present in 1% or more of a population;
phenotype - ANS-any characteristic that can be measured, with the type of
measurement depending on the characteristic.
how can 2 individuals w/ the same mutation have the different severity of disease -
ANS-penetrance: manifestation of disease phenotype under a set of predefined criteria
(% of people who inherit mutation and express associated trait)
Incomplete penetrance of dominantly inherited disease- why deleterious allele persist in
population
- Same mutation can affect different tissues-> different phenotype-> variable
expressivity
Explain the pathophysiologic difference between
mutations that act via loss of function and those that
act via dominant negative gene action - ANS-
Recessive loss of function mutation - ANS-autosomal, classical Mendelian inheritance,
only one allele is working, gives rise to only 50% protein level, need both alleles to
manifest disease phenotype-> recessive inheritance
, Dominant loss of function mutation - ANS-50% protein level= not enough for normal
function->dominance inheritance. most are semidominant w both loss of function alleles
manifesting more severe phenotype
Dominant Negative Gene action - ANS-Involved in genes encoding proteins involved in
oligomeric or polymeric protein complexes
Mutant protein disrupts the formation of normal
protein complexes->inhibiting normal function=dominant inheritance
What are the different mode of inheritance - ANS-- depending on locus of mutated
gene. Autosomal vs X-linked. Autosomal recessive or Dominant. X- linked dominant
fragile X syndrome) or recessive (hemophilia) mostly manifests in men bec of
hemizygosity. Codominance. Maternal inheritance or matroclinous inheritance in
mitochondria.
Leber hereditary optic neuropathy
(LHON - ANS-Mutations in genes located in the mitochondria DNA.
•
Lead to optic cell death and progressive vision loss.
•
Incomplete penetrance: 50% of male and 85% of
female never experience any vision loss of related
health problems.
•
Affected individuals are typically homoplasmy,
heteroplasmy individual will eventually become
homoplasmy
factors that can cause DNA mutation - ANS-- cellular/ metabolism
- UV light exposure
- Ionizing radiation
-chemical exposure
- replication errors (tautomeric shift)
when dna damage is sensed by the cells - ANS-- cellcycle checkpoint axtivation
- transcriptional program activation
- DNA Repair: direct reversal, base excision repair, nucleotide excision repair, mismatch
repair, double stranded break repair (non-homologous end joining or homologous
recombination)
-Apoptosis
