Genetics II Flashcards
Regarding the tri nucleotide repeat associated with Huntington’s disease, it is a…
CAG repeat that occurs in the Exon
CAG repeat occurring in the Exon
Huntington’s disease
What complex in the ETC (respiratory chain of the mitochondria) does NOT contain Mitochondrial DNA?
Complex 2
If a couple both expresses Achondroplasia, what is the chance their offspring will have the lethal form of the gene?
25%
*Both are Heterozygous
Amelogenesia imperfecta with mutation p.Trp153.
What does this indicate?
Stop Codon was Created
c200+IG>A
What kind of mutation is this?
Splicing mutation
If a woman is a carrier for sickle cell and her husband is not, what has happened if her son expresses the trait?
Maternal MII error
*MII will essentially double the error
The repeating CCG expansion of the 5’ UTR found in Fragile X Syndrome have over _____ repeats in affected individuals.
When over this number, _______ causes promoter modification and the cessation of RNA production
200
Methylation
Autosomal Dominant disorders rarely have what mechanism of disease?
What are 3 mechanisms seen in Autosomal dominant diseases?
Loss of Function
Dominant negative, Gain of Function, Haploinsufficiency
Type 1 Osteogenesis imperfecta W/O Dentinogenesis is due to what molecular mechanism?
Haploinsufficiency
Type 1 Osteogenesis imperfecta WITH Dentinogenesis is due to what molecular mechanism?
Dominant Negative
Cystic Fibrosis has different mutations in the same gene giving the same clinical phenotype - what is this called?
Allelic heterogenicity
Different mutations in different genes resulting in the same clinical phenotype is called…
Locus heterogenicity
CGG repeat in the non-coding 5’UTR:
Fragile X
CAG repeat in the 1st exon:
Huntington Disease
GAA repeat in the intron:
Freidreich Ataxia
CTG repeat in the non-coding 3’UTR:
Myotonic Dystrophy
Fragile X:
CGG repeat in the non-coding 5’UTR
Huntington Disease:
CAG repeat in the 1st Exon
Freidreich Ataxia:
GAA repeat in the Intron
Myotonic Dystrophy:
CTG repeat in the non-coding 3’UTR
What is the inheritance pattern for Achondroplasia?
Autosomal Dominant
*Fibroblast Growth Factor Receptror 3
_____% of individuals affected with Achondroplasia are de novo mutations on the _______ chromosome
80
paternal
The majority of individuals affected with Achondroplasia have a ______ to ______ substitution at codon 380.
Glycine
Arginine
99% of Achondroplasia is a ___ to ____ transition (purine for purine
1% of Achondroplasia is a ___ to ____ transversion (purine to pyrimidine)
G to A
G to C
T/F
Mutations causing Achondroplasia can cause an alteration of restriction sites leading to shorter DNA fragments
T/F
Mutations causing Achondroplasia can lead to “gain of function” - new or enhanced function of the gene
True
True
How is Achondroplasia diagnosed?
PCR
Huntington’s disease is what type?
Autosomal Dominant
The age of onset changing in a disease indicates what?
Anticipation
Differential inheritance from mother or father indicates what?
Imprinting
T/F
Huntington’s exhibits both Anticipation and Imprinting:
True
If No band is visible in Fragile X testing, the male is either ______ or ______.
Premutation
Full mutation carrier
If someone has inherited a mutant allele but isn’t expressing the phenotype, this may be an example of…
Penetrance (or non-penetrance)
***light switch
If someone has inherited a mutant allele and may express the trait to variable degrees (different severity), this is an example of…
Variable Expressivity
The increased severity and/or decreased age of onset of disease with successive generations is…
Anticipation
What reflects an increased number of repeats passed from generation to generation?
Anticipation
What is the differential modification and expression of alleles of genes depending on the Sex of the parent of origin?
(it matters who gives you what)
Imprinting
Prader-Willi and Angleman are best examples of what?
Imprinting
How many human genes have been discovered that show Imprinting expression?
31
Inheritance of 2 copies of a gene/chromosome from one parent is called what?
This has implications for what kind of disorders?
Uniparental Disomy
Recessive and Imprinted disorders
Fragile X testing, 60-200 copies is…
Premutation
Fragile X testing, over 230 copies is…
Full mutation carrier
A PCR test for Fragile X will only detect up to 100 copies, if someone has the mutation, what test will confirm?
Southern Blot
What type of genetics has a high mutation rate, limited proofreading/repair, and lack of protective histones?
Mitochondrial
Define MItochondrial Heteroplasmy:
Both wildtype and mutant mito DNA
What is the Threshold Effect of Mitochondrial DNA?
Certain min. number of mutant proteins must be present before Expression occurs
T/F
Mitotic Segregation occurs in Mitochondrial genetics
True
p.Gly17Arg
AA substitution
Missense
***point mutation
p.Gly17*
Stop Codon
Nonsense
- = stop
p.Leu6Hisfs*3
Frameshift mutation
either deletion or duplication has occurred, now there’s a Stop codon
De Novo mutation on Mom’s allele:
NOT Achondroplasia
Achondroplasia detected by:
PCR restriction detection
Achondroplasia AA consequence:
AA lethal
c.101-2A>T
Splicing
T/F
Penetrance is binary
True
Either are or aren’t penetrant
T/F
Variable expressivity is a function of penetrance
True
What needs to occur for Uniparental Disomy to take effect?
Must kick out other paren’t chromosome
*otherwise trisomy
Mitochondrial Heteroplasmy =
wildtype and mutant DNA
T/F
Mitochondrial DNA has bigger mutation rate because no histones, no proofreading, and is at a site of radical oxidative formation
True
Beginning with a single DNA strand, how many cycles of PCR = 1 million copies
20
If a woman has 2 populations of mitochondrial DNA, one of which contains a mutation, this is an example of…
Heteroplasmy
