Genetics 1- 10

Question 1

Sildenafil (Viagara) works by

Answer 1

blocking the enzyme PDE5, which relaxes arteries & results in increased blood flow

Question 2

Transformation

Answer 2

ability to deliver foreign DNA to cells, both prokaryotic and eukaryotic

Question 3

Plasmid

Answer 3

Autonomously replicating DNA molecule; single origin of replication & can replicate itself in bacterial cells

Question 4

Restriction endonucleases (enzymes)

Answer 4

molecular scissors to selectively cut DNA

Question 5

Selection

Answer 5

methods to rapidly select those host cells that contain recombinant DNA

Question 6

Personal genomics

Answer 6

branch of genomics where the genotyping stage employs single-nucleotide polymorphsm (SNP) analysis (0.2%of genome) or partial/full genome sequencing

Question 7

Kinetochore

Answer 7

repeated sequence known as alpha satellite DNA

Question 8

Telomere length is controlled by

Answer 8

erosion and addition

Question 9

Chronic myeloid leukemia (CML)

Answer 9

malignant transformation of hematopoietic stem cells; accounts for 20% of all adult leukemias

caused by translocation between chromosomes 9 and 22 (BCR-ABL oncogene creation). Philadelphia chromosome!

Question 10

CML is classified into three phases

Answer 10

chronic phase (less than 10% blasts), accelerated phase (10-20% blasts), and blastic phase (20% or more). These phases are based mainly on the number of immature white blood cells, myeoblasts, seen in the blood or bone marrow

Chronic is the most treatable phase

Question 11

Philadelphia Chromosome

Answer 11

a reciprocal translocation between chromosomes 9 and 22

The ABL1 proto-oncogene encodes a cytoplasmic and nuclear protein tyrosine kinase; it is moved adjacent to BCR (breakpoint cluster region protein) on chromosome 22

BCR-ABL is a mutant tyrosine kinase that stimulates uncontrolled cell division of abnormal blood cells by the bone marrow

Question 12

Epigenetics

Answer 12

heritable alternations in gene expression, which are not due to structural changes in the DNA; induced spontaneously

Methylation (turns gene off)
Acetylation (turns gene on)
Phosphorylation (positive and negative consequences)
Ubiquination (targets histones for degradation)
Sumolaytion (promotes gene silencing by affecting histones)

Question 13

Functions of DNA methylation in mammals

Answer 13

Transcription gene silencing
genome stability
chromatin compaction
X chromosome inactivation (females)

Question 14

Etopside (VP-16)

Answer 14

derivative of podophyllotoxin from the mandrake plant
etopside inhibits the re-ligation of the strands resulting in the accumulation or irreversible double strand breaks lethal to cells

Question 15

snRNA

Answer 15

small nuclear RNAs, complexed with protein in the nucleus, invovled in RNA splicing

Question 16

snoRNAs

Answer 16

small nucleolar RNAs, used to process and chemically modify rRNAS

Question 17

Spinal Muscular Atrophy (SMA)

Answer 17

Second most-common recessive human disorder and the most common inherited cause of infant mortality

Mutations in the SMN1 encoding the survival motor neuron (SMN) protein cause SMA

SMN is needed in pre-RNA splicing

SMN2 is already damaged in us so it can’t make up for a errors in SMN1

Question 18

Cryptic splice site

Answer 18

a randomly occurring site in the genome that contains a consensus sequence for 5’ or 3’ intron splicing but is not normally used for that purpose, until mutated

ex: progeria

Question 19

Hutchinson-Gilford progeria syndrome (HGPS)

Answer 19

a point mutation activates a cryptic splice site and thus leads to the production of a mutant prelamin A protein, progerin. An internal cleavage site is removed, and the progerin protein is never properly cleaved (leaving it permanently farnesylated and carboxymethylated)

Question 20

ncRNA (non-coding RNA)

Answer 20

a functional RNA molecule that is not translated into a protein

ex: rRNA, tRNA, snoRNA, microRNA, siRNA, piRNA, and long ncRNAs

Question 21

Xist

Answer 21

non-coding RNA gene on the X chromosome that participates in X chromosome inactivation

Question 22

miRNA

Answer 22

post-transcriptional regulators that bind to complementary sequences in multiple target mRNAS, usually resulting in translation repression or target degradation and gene silencing

(Dicer chops it up and then miRNA complexes with the RISC complex to attack mRNA)

Question 23

siRNA

Answer 23

Small Interfering RNA - double-stranded RNA molecules that can be chemically synthesized and are used in therapeutic gene silencing (similar function to miRNA)

Question 24

Gene drive

Answer 24

genetic systems that circumvent the traditional rules (50% chance of inheriting genes from either parent); they greatly increase the odds that the drive will be passed onto offspring

“Cas9 to the nth degree,” “eliminating Mendellian genetics”

Question 25

circular RNA

Answer 25

ciRNAs might modulate RNA polymerase II in cis and thereby alter the expression of their gene. ciRNAs also accumulate in the nucleus and can be localized to their sites of transcription function as an miRNA sponge?

Question 26

centimorgan (cM)

Answer 26

the genetic distance between two loci that yields recombination in 1% of gametes

Question 27

LOD score

Answer 27

statistical measure of the likelihood of odds that the observed marker is indeed linked and not inherited with disease by chance

Question 28

SNVs

Answer 28

single nucleotide variation seen in a single family or individual

Question 29

CNVs

Answer 29

copy number variations - duplications or deletions, often 1000 to several million bp

Question 30

Genome-Wide Association Study (GWAS)

Answer 30

how we map for polygenic traits compare 100,000s of polymorphisms between cases and controls and identifies SNPs frequently associated with case

Question 31

Levels of gene expression control in eukaryotes

Answer 31

1. Chromatin structure 2. Epigenetics control 3. Transcriptional initiation 4. Transcript processing and modification 5. RNA transport 6. Transcript stability 7. Control of transcript mRNA levels by non-coding RNAs 8. Post-translational modification 9. Protein transport 10. Control of protein stability

Question 32

Regulation of transcriptional activators

Answer 32

1. Phosphorylation stimulates cytoplasmic proteins to move to the nucleus 2. Ligand binding increases or decreases affinity for DNA 3. Some are already bound to their target site but remain inactive until they are stimualted

Question 33

3 parts of a nuclear hormone receptor

Answer 33

1. AD - activation domain 2. DBD - DNA binding domain 3. LBD - ligand binding domain

Question 34

Burkitt Lymphoma

Answer 34

A very fast growing version of non-Hodgkin's lymphoma. Caused by reciprocal translocation of the c-Myc locus on chromosome 8 with iG enhancer on chromosome 14.

Question 35

Three clinical variants of Burkitt lymphoma

Answer 35

1. Endemic - equatorial Africa along with Epstein-Barr virus 2. Sporadic - outside Africa 3. Immunodeficiency - usually associated with HIV or in post-transplant patients

Question 36

Penetrance

Answer 36

the percentage of individuals of a specific genotype showing the expected phenotype can be fully penetrant (always expressed) or incompletely penetrant (only shown sometimes)

Question 37

Expressivity

Answer 37

measures the extent to which a given genotype is expressed in the phenotype (variability of a trait based upon a specific genotype)

Question 38

Roberts syndrome (RBS)

Answer 38

caused by a mutation in ESCO2, a human homolog of yeast ECO1, that is essential for the establishment of sister chromatid cohesion RBS cells have too few or too many chromosomes that ultimately lead to aborted cell divisions Present with hands and feet attached to abbreviated arms and legs (phocomelia)

Question 39

Phocomelia

Answer 39

congenital malformation in which hands and feet are attached to abbreviated arms and legs Seen in Roberts Syndrome (RBS)

Question 40

Harlequin ichthyosis (HI)

Answer 40

severe, often fatal congenital ichthyosis with an autosomal recessive inheritance pattern caused by a defect in the ATP-binding cassette transporter ABCA12 presents with hyperkeratosis, ectropion, and eclabium

Question 41

hyperkeratosis

Answer 41

thickening of the stratum corneum, the outermost layer of the epidermis (fissures all over the body)

Question 42

ectropion

Answer 42

lower eyelid turns outward

Question 43

eclabium

Answer 43

the lips turn outward

Question 44

"Second hits" in retinoblastoma

Answer 44

non-disjunction, non-disjunction reduplication, mitotic recombination, gene conversion, deletion, and point mutation

Question 45

genetic imprinting

Answer 45

differential expression of a gene or chromosome region, according to the parent-of-origin of the allele one parent's allele is selectively silenced "functional hemizygosity"

Question 46

hydatiform mole

Answer 46

two sets of paternal chromosomes only

Question 47

ovarian teratoma

Answer 47

two sets of maternal chromosomes only

Question 48

Prader-Willi Syndrome (PWS)

Answer 48

Paternal-only genes on chromosome 15 fail to be expressed

Question 49

Angelman Syndrome

Answer 49

Maternal-only gene UBE3A on chromosome 15 fails to be expressed

Question 50

Four genetic mechanisms to PWS & Angelman

Answer 50

1. Deletion (usually in a long-copy repeat area) 2. Uniparental disomy (two copies of the chromosome from one parent) 3. Mutation (more common in Angelman than PWS) 4. Imprinting defect

Question 51

Epigenotype

Answer 51

epigenetic parent of origin information typically reprogrammed between generations

Question 52

Myotonic Dystrophy Type 1 is caused by

Answer 52

Expanded CTG repeats in the 3' UTR. Mild affect is 50-80 repeats. Severe is over 2000 repeats. CTG repeat length correlates with age of onset (more repeats, earlier age) These CTG repeats are transcribed into CUG repeats. The CUG RNA sequesters RNA binding proteins like MBNL. MBNL can now no longer perform its alternative splicing function, and muscle cells revert to fetal-like muscle cells which causes rigidity and myotonia

Question 53

cytogenetics

Answer 53

brand of genetics focused on the structure and function of chromosomes

Question 54

G-banding detects the following cytogenetic anomalies:

Answer 54

1. Deletions > 5Mb 2. Some translocations 3. Aneuploidy 4. Mosaicism 5. Ring, marker, and isochromosomes (fragments)

Question 55

Acrocentric chromosomes

Answer 55

13, 14, 15, 21, and 22

Question 56

Aneuploidy

Answer 56

abnormal number of chromosomes

Question 57

Edward's Syndrome

Answer 57

Trisomy 18 rare to survive until 6 months, often stillborn. Low birth weight, cleft palate, heart & kidney defects, irregularly shaped head

Question 58

Triploidy

Answer 58

three sets of chromosomes 85% are diandric (2 paternal). These fetuses are near normal size. 15% are digynic (2 maternal). These fetuses have intrauterine growth retardation.

Question 59

Unbalanced translocations

Answer 59

Arise from fertilization of a gamete with a balanced translocation Result may be 46 chromosomes but monosomy and trisomy for some segments 80-90% are usually normal, whereas theoretical outcome would be 25%

Question 60

Robertsonian translocations

Answer 60

Between acrocentric chromosomes Breakpoints at or near centromere and yield a metacentric or submetacentric chromosome (often dicentic) Creates one giant chromosome and then a fragment piece thats usually lost

Question 61

Paracentric inversion

Answer 61

within one arm of chromosome risk for liveborn children is low (but 50% are often not viable due to acentricity or dicentricity)

Question 62

Pericentric

Answer 62

inversion involving the centromere risk for offspring is similar to balanced translocation often less severe than paracentric because all chromosomes end up with a centromere

Question 63

Primary mechanism of duplications and deletions

Answer 63

nonallelic recombination between low copy repeats

Question 64

Marker chromosome

Answer 64

structurally abnormal chromosome often of unknown origin ex: Cat Eye Syndrome

Question 65

Isochromosome

Answer 65

Separation along the wrong axis in anaphase creates a chromosome that is p/p or q/q ex: Pallister-Killian Syndrome is a isochromosome tetrasomy of 12p

Question 66

Ring chromosome

Answer 66

Breaks on both p and q arms, ends fuse Mitotically unstable Yields a "dynamic mosaicism" Heritable ex: 6% of Turner syndrome cases are due to a ring X chromosome [ 46,X, r(X) ]

Question 67

Mosaicism

Answer 67

individual with 2 or more genetically different cell varieties; cell types differ due to mutation or nondisjunction

Question 68

Cytogenetic technologies

Answer 68

FISH Microarray SNP microarray MS-MLPA

Question 69

FISH

Answer 69

Fluorescence in situ hybridization Clinical applications: aneuploidy, microdeletions and duplications, marker chromosome, and to refine breakpoints of insertions, deletions, translocations, etc Benefits: rapid analysis for high risk pregnancies Limitations: may not detect low-level mosaicism or structural chromosome anomalies (only sees region complementary to probe)

Question 70

Charcot-Marie Tooth Type 1A

Answer 70

LCR-mediated duplication on chromosome 17 Demyelinating peripheral neuropathy, progressive distal muscle weakness and atrophy, sensory loss and slow nerve conduction

Question 71

Comparative Genome Hybridization (CGH)

Answer 71

Chromosome microarray where subject DNA is hybridized with reference DNA and applied to an array. You compare and can tell if there is an extra copy or missing copy. Great for high resolution of location/breakpoints of deletions or duplications Will NOT detect balanced translocations

Question 72

Chromosome microarray - SNP array

Answer 72

Detects variants (consanguinity) and copy number. The resolution is determined by the density of SNPs

Question 73

Benefits of microarrays

Answer 73

high resolution, objectivity, nondividing tissue, detect several disorders at one time

Question 74

Limitations of microarrays

Answer 74

Does not detect balanced rearrangements or point mutations; detects copy number variation of uncertain signifigance

Question 75

isodisomy

Answer 75

two copies of the same homolog from one parent

Question 76

Heterodisomy

Answer 76

two different homologs from one parent

Question 77

Factors affecting pathogenicity of anomalies

Answer 77

Extent of genome affected, location in genome, inherited vs. de novo

Question 78

DNA primase does what?

Answer 78

Makes RNA primer that initiates DNA replication

Question 79

Components of a human gene

Answer 79

Exons, Introns, a transcription start site, a promoter (base or core promoter AND an "upstream" promoter), TATA Box (positions RNAPII) and enhancers

Question 80

Factors influencing penetrance

Answer 80

1. modifier genes 2. Response to DNA damage 3. Epigenetic factors: DNA methylation 4. Age-related penetrance

Question 81

Types of nonmendelian inheritance

Answer 81

triplet repeats, genomic imprinting, mosaicism, mitochondrial inheritance

Question 82

Chromosomes are always named after what?

Answer 82

The source of the centromere

Question 83

Unbalanced translocations arise from what?

Answer 83

The fertilization of a gamete with a balanced translocation

Question 84

Limitations of microarrays?

Answer 84

Do not detect balanced rearrangements or point mutations Detects copy number variations of uncertain significance