Genetics Flashcards
Who are bi-cyclic: purines or pyrimidines?
Purines [A, G]
Phosphodiester bonds are catalyzed by which enzymes?
DNA/RNA ; DNA ligase
Which bases hydrogen bond 3 times vs 2? AT or GC
GC bonds 3x H
DNA exterior is + or - charged at physiological pH?
Negative
If a sample of DNA contains 35% adenine, what % of other nucleotides? What is this rule called?
35% T
15% C; 15% G
* Chargaff’s rules
Which is more unstable: RNA or DNA
RNA [used within hours to days]; bacterial RNA used and degraded within minutes
Post-transcriptional modifications include:
- Addition of 5’ cap, 3’ poly-A tail
2. Splicing of introns out
Capping of eukaryotic mRNA occurs by addition of ___________. What is the function of the cap?
7-methyl-guanosine
* Regulates export out of nucleus; translation; slows degradation
What are the functions of the 3’ mRNA poly-A tail?
Increases t1/2 by protecting it from enzymatic degradation in the cytoplasm; interacts with 5’ cap which aids in export of mRNA from nucleus
Splicing removes introns or exons? What is another name for a splice site? 5’ donor always has; 3’ acceptor has:
Introns; consensus sequence
5’: GU
3’ AG
T/F 60% of human genes are spliced in alternative ways to allow for production of different set of mRNA.
True: altered function, tissue-specific isoforms, alternative intracellular localization, membrane-bound and soluble forms
What is the classiscal example of mRNA editing?
Editing of apolipoprotein-B mRNA. Liver = B-100; Intestine: B-48
What comes first: donor or acceptor site when considering splicing of introns?
Donor followed by acceptor
Differentiate between RNA pol 1, 2, 3
RNA pol 1: rRNA [most abundant]
RNA pol 2: mRNA
RNA pol 3: tRNA
Alpha-amanatin [poison deathcap mushroom] inhibits which RNA polymerase?
RNA pol 2
Do promotors contact RNA pol 2 directly?
No, they use transcription factors
What are several examples of sequences within eukaryotic promotor regions that are recognized by RNA polymerase 2?
CAAT box; TATA box
* Basal transcription machinery also
T/F Enhancer sequences may be very far away from transcription start sites. What do enhancers bind to?
True; activators
Molecular mechanism of DMD vs. BMD
DMD: deletion/stop codon (frame-shift)
BMD: missense (in frame)
What is the function of dystrophin protein?
Links the actin cytoskeleton with protein complexes that are associated with sarcolemma membrane; provides cell integrity.
T/F PCR may not detect heterozygotes. What is a way around this?
True; multiplex ligation dependent probe amplication PCR.
How can females display DMD symptoms?
In the manifesting heterozygote female, there are tissues that are healthy while others are badly affected; functional mosaicism
The most common lethal inherited disease in Caucasians?
Cystic fibrosis
The principal cause of death in CF
End stage lung disease
In the chloride sweat test, what drug is used to stmulate the sweat glands?
Pilocarpine (muscarinic agonist)
The COL1A1 gene mutation can lead to…
OI
Mutations in SERPINA1 gene lead to…
A1AT (Serine protease inhibitor); loss of neutrophil elastase inhibition
The characteristic genetic principle demonstrated through triplet repeat expansion disorders is:
Anticipation [age of onset and severity becomes earlier in subsequent generations]
Repeat sequence: Huntington disease
CAG [protein coding]
Repeat sequence: Fragile X Syndrome
CGG
Repeat sequence & inheritance of: Myotonic dystrophy
CTG [AD]
Is there a gain of function mutation associated with Huntington disease?
Yes: polyglutamine repeat
The CAG repeat expansion occurs during male gametogenesis in this disorder. This is an example of meiotic drive, whereby germ cells that contain expanded repeats can have a selective advantage.
Huntington disease (in myotonic dystrophy, the CTG repeat can also lead to meiotic drive).
Intellectual disability, learning difficulties, elongated face, low muscle tone, flat feet and macroorchidism
Fragile X Syndrome (X-linked Dominant inheritance) CGG
Name the major triplet repeat expansion disorders and their triplets.
Fragile X: CGG
Huntington: CAG
MD: CTG
What is an example of an X-linked dominant mutation? This condition leads to methylation mediated epigenetic gene silencing
Fragile X syndrome
Reduced expression of the FMR1 gene
Fragile X syndrome
T/F Maternal anticipation results in highest triplet expansions in myotonic dystrophy
T
DMPK mutation results in
Myotonic dystrophy (CTG repeat)
Lack of muscle coordination during voluntary movments, vision impairment, scoliosis, DM, heart disorders
Freidreich ataxia [frataxin gene]; involves mitochondrial iron metabolism that leads to the formation of heterochromatin
Anencephaly refers to the congenital absence of the cranial vault. It is a sysraphic anomaly of neural tube closure that results from an injury to the fetus when?
During 23-26th day of gestation
Disfiguring neurofibromas, cafe au Lait spots, pigmented lesions of iris is due to the loss of which tumor supressor gene?
NF-1: GTPase-activating protein
What is one of the major complications of NF1?
Neurofibrosarcoma; meningioma, optic glioma, pheochromcytoma
The hallmark of this lysosomal storage disease is the presence of lipid-laden macrophages [wrinkled tissue paper] that are characteristically present in the red pulp of the spleen, liver sinusoids, lymph nodes, lungs, bone marrow.
Gaucher disease [also bone pain]
Anasarca in an erythroblastalis fetalis baby is 2/2
CHF
Which serum Ig crosses the placenta?
IgG
A 19-year-old man is referred to a neurologist because of failing eyesight and progressive muscle weakness. The
neurologist takes a history and finds that several of the patient’s male and female relatives have similar symptoms. His
mother, her brother and sister, and two of the aunt’s children are affected, but the uncle’s children are not. What is the inheritance pattern?
Mitochondrial
Androgen insensitivity is also called
Testicular feminization
Gene sequence:
5’—-TAAGCCAATTGG—-3’
Sequence of the primer for PCR or ASO probe?
5‟—-CCAATTGGCTTA—-3‟
T/F Epigenetic modifications such as methylation regulate the rate at which transcription occurs
True
Give serveral examples of extragenic DNA.
Tandem repeat
* Satellite, minisatellite (telomeric, hypervariable), microsatelliite
Interspersed
Where is the highest gene density in DNA?
Sub-telomeric
Are heterochromatic and centromeric regions of DNA coding or non-coding?
Non-coding
Nuclear DNA can be divided into what 2 types of genes
- Single copy: single protein
- Multigene families
- Classic: HOX [high homology]
- Superfamilies: HLA, TCR [limited homology]
What % of DNA is protein coding?
<2%
Variable number of tandem repeats (VNTR) and short tandem repeats (STR) are inherited in what fashion?
Co-dominant [used for DNA fingerprinting]
Minisatellite vs. Microsatellite
Mini: Telomeric; hypervariable (6NT)
Micro: Very short sequences (2NT); short tandem repeat – trinucleotide expansion diseases
Trinucleotide repeat expansion diseases are associated with which aspect of a chromosome?
Microsatellite
What are SINES and LINES?
Short and Long interspersed nuclear elements; some have RT activity; responsible for many of the mutations that have arisen 2/2 unequal crossover during meiosis.
Short arm vs. Long Arm of a chromsome
P arm: short arm
Q arm: long arm
A research geneticist has identified a
tetranucleotide repeat polymorphic marker, that
is linked to an autosomal dominant disorder in a
family. This marker belongs to the class of:
Microsatellite DNA
T/F Genes are generally absent in the telomeres and centromere.
True
Differentiate between: metacentric, submetacentric, and acrocentric chromosomes.
Metacentric: p = q
Submetacentric: p shorter than q
Acrocentric: p contains very little information
What types of chromosomes are involved in Robertsonian translocations?
Acrocentric chromosomes: p arm contains very little genetic information
Karyotyping is viewed during what phase of the cell cycle?
Metaphase
When both the chromosomes of the pair are derived from the same parent, it is said to be called
Uniparental disomy
T/F X-inactivation is fixed: the same X chromosome is inactivated in all the descendants of the cell.
True
X-inactivation is regulated by a region on the chromosome called..
X-inactivation center: XIST
Methylation of _____________ bases, also called _______ islands, close to the promotor, results in transcriptional repression.
Cytosine bases; CG islands
The process of ___________ is similar to X-inactivation, in that the imprinted gene is methylated and transcriptionally silenced
Imprinting
Locus of a gene
Refers to its location on a chromosome
Maximum time in the cell cycle is spent in: interphase or mitosis
Interphase
Give examples of labile, stable and permanent cells
Labile: Skin, GIT, epithelial
Stable: Liver
Permanent: Neuron, cardiac muscle
The important G1-S checkpoint proteins
p53 & Rb
What molecules regulate the entry of cells into the various phases of the cell cycle?
Cyclins
What phase of the cell cycle? Nuclear envelope dissolves. Mitotic spindle forms, chromosomes start condensing and become visible; chromosomes start binding to the spindle
Prophase
What phase of the cell cycle? Separation of sister chromatids
Anaphase
What are the major events of meiosis 1 & 2?
1: Homologous chromosomes separate
2: Sister chromatids separate
During meiosis 1 non-disjunction…
Homologs do not separate
During meiosis 2 non-disjunction…
Sister chromatids do not separate
Male vs. Female: When does gametogenesis commence?
Male: Puberty
Female: Early embryonic life
In a female, oocytes are arrested in… until ovulation.
Prophase I
T/F There is a higher risk of maternal non-disjunction in meiosis, resulting in a higher risk of trisomy.
T
T/F A higher paternal age can result in the development of new dominant single gene mutations.
T
Locus vs. Allele
Locus: location of a gene
Allele: one of the alternative forms of a gene that occur at a locus
AD disorders manifest in the homo/hetero-zygous state?
Heterozygous
Is male-to-male inheritance seen in AD conditions?
Yes
Inheritance: Familial hypercholesterolemia (LDL R deficiency)
AD
Inheritance: Huntington disease
AD
Inheritance: Myotonic dystrophy
AD
Inheritance: Marfan syndrome
AD
Inheritance: OI
AD
Inheritance: Achondroplasia
AD
Inheritance: NF-1
AD
Inheritance: Acute intermittent porphyria
AD
AD mutation in the DMPK gene; most pleiotropic phenotype of all unstable 3xrepeat disorders; characterized by wasting of muscles, cataracts, heart conduction defects, endocrine defects, myotonia
Myotonic dystrophy
AD FGFR3 mutation
Achondroplasia
NF-1 is caused by different mutations in the NF-1 gene. What is this called? Locus or Allelic heterogeneity
Allelic heterogeneity
Horizontal inheritance: AR or AD
AR
In AR sibships, what proportion of non-affected siblings are carriers?
2/3
Inheritance: CF
AR
Inheritance: SCA
AR
Inheritance: PKU
AR
Inheritance: Tay Sachs
AR
Inheritance: Congenital deafness
AR
Inheritance: Hemochromatosis
AR
The most common mutation of the HFE gene?
C282Y mutation
What are several reasons for pseudo-autosomal dominant inheritance?
High carrier frequency, birth of an affected child to an affected individual, consanguinity
Inheritance pattern of blood types
Co-dominance
Is male-to-male inheritance seen in X-linked recessive disorders?
No
Inheritance: Duchenne & Becker muscular dystrophy
X-linked recessive
Inheritance: G6PD deficiency
X-linked recessive
Inheritance: Hemophilia A & B
X-linked recessive
Inheritance: Lesch-Nyhan syndrome
X-linked recessive
Inheritance: Red-green color blindness
X-linked recessive
Several possible explanations for a manifesting heterozygote in an X-linked recessive disorder
- Skewed inactivation
- Presence of two mutant copies (dad + mom)
- Female with only copy of the X-chromosome
In X-linked dominant disorders, there is a preponderance of females compared to males.
Females; male transmits the disease to all his daughters; none of his sons are affected
Inheritance: Vitamin D resistant rickets
X-linked Dominant
Inheritance: Incontinentia pigmenti
X-linked Dominant
Y-linked inheritance genes are usually not passed on b/c they cause sterility. 2 Examples of Y-linked inheritance
Mutations in SRY gene; H-Y histocompatibility Ag
Hemochromatosis is more severe in males. This is known as:
Variable expression
Xeroderma pigmentosum is more severe in individuals exposed more frequently to UV radiation. This is known as:
Variable expression
A disease causing a mutation that affects multiple organ systems, i.e. Marfan syndrome or OI is known as
Pleiotrophic
Pleiotrophic disease
One mutation affects multiple organ systems: Marfan, OI
Mutations on chromosome 17 or 7 can lead to the manifestations of osteogenesis imperfecta. This is known as: ________. Other examples include: CMT disease, sensorineural hearing, retinitis pigmentosa
Locus heterogeneity.
T/F Allelic heterogeneity can lead to compound heterozygosity.
True
A 23 year old female is pregnant and has come for genetic
counseling. Her father (50 years) is diagnosed to have
Huntington’s disease. What is her risk of transmitting the mutant
gene to her child?
50% * 50% = 25%
In Huntington’s disease, the disorder is generally more severe if transmitted from the father
True
The severity of mitochondrial disorders can vary in individuals with the disorder. This is due to the phenomenon of:
Heteroplasmy
Inheritance: Leber hereditary optic neuropathy
Mitochondrial
Inheritance: MELAS / Mitochondrial encephalopathy, lactic acidosis, stroke
Mitochondrial
Inheritance: MERRF / Myoclonic epilepsy with ragged red muscle fibers
Mitochondrial
Triplet repeat disoders: Promoter, Intron, Coding, 3’ end
Promoter: Fragile X
Intron: Friedrich ataxia
Coding: Huntington
3’: Myotonic dystrophy
Triplet repeat of FMR1 gene
Fragile X syndrome
Deletion of paternal 15q11-13 (absence of SNRPN) results in
Prader-Willi syndrome [obese, mental delay, underdeveloped genitalia]
* Typically, the chromosome is imprinted in the mother
Describe the phenomenon of trisomy rescue and its relationship to uniparental disomy
You actually have an extra copy of the chromosome
Deletion of maternal 15q11-13 (absence of UBE3A) results in
Angelman syndrome: Happy puppet syndrome
Mutations in 2 genes are additive and necessary to produce the disoder. One example of this type of digenic inheritance is…
Retinitis pigmentosa
