Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

MS1 Fall > Genetics 11 - 20 > Flashcards

Genetics 11 - 20 Flashcards

1
Q

Fragile X (prevalence and cause)

A

1/3500 males, 1/6000 females

Expanded CGG repeats in the FMRP 5’ UTR gene leads to hypermethylation and transcriptional shutdown

X-linked dominant inheritance (more common in males)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Fragile X clinical presentation

A

intellectual disability, autism spectrum, elongated faces, large ears, macroorchidism (large testicles)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Fragile X Associated Tremor/Ataxia Syndrome (FXTAS)

A

Late adult onset (over 50 usually). Will see Grandfathers have this - indicative of genetic anticipation

Causes tremor and ataxia (loss of control of body movements)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Fragile X Summary

A

Expanded CGG repeats -> hypermethylation of the FMRP 5’ UTR -> Loss of FMRP protein -> increased production of specific synaptic proteins (glutamate receptors) and loss of ability to regulate synaptic biology

** Example of DNA path

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Myotonic Dystrophy Summary

A

Expanded CTG repeat -> Transcribed into expanded CUG repeats -> Sequestration of MBNL proteins -> Widespread changes in MBNL-mediated RNA splicing and RNA metabolism (the exon that is supposed to be excised isn’t!)

** Example of RNA path

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Huntington’s Disease symptoms

A

Motor (chorea, delayed and reduced velocity, dystonia, rigidity), cognitive (difficulty searching memory, executive dysfunction), psychiatric (depressed mood, anxiety, irritability, increased risk for suicide)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Huntington’s Disease Summary

A

Expanded CAG repeat -> Transcribed and translated into polyglutamine repeats -> myriad of downstream consequences, protein aggregates, etc - > cell death (dramatic loss of striatal neurons in the brain)

** Example of protein path

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Most common form of familial amyotrophic lateral sclerosis

A

C9ORF72/ALS/FTD

FTD = fronto-temporal dementia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

C9ORF72/ALS/FTD

A

G4C2 and C4G2 antisense transcripts are produced. These transcripts form RNA foci.

Ribosomes initiate on these repeats without an AUG/start codon and various, toxic dipeptide repeats are created.

Still unknown whether its the toxic RNA, toxic protein, or both that contribute to the disease.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Most repeat expansion diseases are: dominant or recessive?

A

Dominant

Friedreich’s Ataxia is recessive

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Hemoglobin S

A

Mutation in the beta-globin gene (valine for a glutamine)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Clinical manifestations of Sickle Cell Disease

A

Every organ in the body can be affected

  • Anemia (reduced RBC life span, hemolysis)
  • Vaso-occlusion most common clinical complication. No biomarkers to check for this. Believe the patient
  • Vasculopathy (changes in the blood vessel wall)
  • Strokes
  • Loss of vision
  • Acute chest syndrome
  • Gallstones (cholelithiasis)
  • Liver & kidney failure
  • Splenic infarction (prevent with vaccinations and prophylactic antibiotics
  • Leg ulcers
  • Priapism (sustained erection)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Hydroxyurea

A

Used to treat SCD

Decreases painful episodes, hospitalizations, chest syndrome, and extends life

Acts by increasing the amount of HbF in the blood (exact mechanism unknown)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Clinical Interventions for SCD

A

immunizations, penicillin prophylaxis, stem cell transplant, RBC transfusions, hydroxyurea, L-glutamine powder

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Heteroplasmy

A

More than one species of mitochondrial DNA per cell (mtDNA)

In dividing cells it leads to somatic mosaicism. When cells are partitioned during cytokinesis, some get higher levels of mutant mitochondria than others

Also often results from high mtDNA mutation rate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Homoplasmy

A

Uniformity of mitochondrial DNA (mtDNA)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

How do mitochondrial diseases become established in families?

A

It’s a two generation process from mutated mtDNA to affected individual

If a blastomere with mutated mtDNA becomes a primordial germ cell, then the gamete of that individual will ultimately be affected

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Mitochondrial diseases

A

About 40, very rare. Variable severity within families. Affects tissues with high energy requirements: muscle and nerve

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Dosage compensation

A

Equalization of expression between XX and XY

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

X Chromosome inactivation happens when?

A

Occurs in blastomeres in early embryonic development

Random and irreversible. Decision is made independently in each cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Mechanism of X inactivation

A
  1. Initiation (counting, selecting, inactivating)
    * * The X chromosome bound by blocking factors (created by autosomes) remains active
    * * Xist and Tsix compete (Xist prevails on inactive, Tsix prevails on active)
  2. Establishment, spreading of inactivation from “inactivation center”
  3. Maintenance during subsequent mitotic divisions
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Turner Syndrome

A

45,XO

Short stature, webbing of the neck, amenorrhea, normal intelligence

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Klinefelter Syndrome

A

47, XXY

Tall, hypogonadism, some learning difficulties

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Trisomy X (Triplo X)

A

47, XXX

Tall, variably reduced intelligence, may be fertile

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What percentage of genes on the X chromosome normally escape X inactivation?

A

15%

What causes issues in Turner Syndrome (not enough gene product) and Trisomy X (too much gene product)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Basic Properties of Enzymes

A
  • They enhance reactivity (acceleration reaction rate). ALWAYS to the same extent in forward and reverse directions
  • They exert absolutely NO effect on the reaction equilibrium
  • Lower the activation energy that reactants must surmount for a rxn to occur
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Mutations in enzymes can affect:

A
  1. Rates of substrate binding
  2. pKa’s of catalytic ionic groups
  3. Metal ion interactions
  4. Rates of product release
  5. Conformational changes

NEVER RXN EQUILIBRIUM CONSTANT

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

A mutation that decreases Km will

A

Increase activity

Because it now takes less substrate to reach half maximal velocity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

A mutation that increases Km will

A

Decrease activity

Because it now takes more substrate to reach half maximal velocity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Other enzyme mutational effects

A
  • Change allosteric properties
  • Alter enzyme polymerization
  • Loss of organelle-targeting sequence
  • Altered posttranslational modifications
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Imatinib (Gleevec)

A

used in the treatment of CML (Philadelphia chromosome! 9 & 22)

Binds to the inactive form of the c-Abl protein kinase (in Bcr-Abl) and blocks cell motility. Very successful in long-term management of the disease, unless drug resistance mutations occur

32
Q

Isozymes

A

Different proteins catalyzing same reaction

33
Q

Alterations in T0 state stability

A

If T0 is much more stable than R0, then the molecule has a reduced affinity for O2. Harder to bind O2, easier to release. This shifts the O2 curve to the right (affinity for O2 has been reduced).

If T0 is slightly more stable than R0, than there is an increased affinity for O2. Easier to bind O2, but harder to release. This shifts the O2 curve to the left and makes it more hyperbolic (increased affinity for O2).

34
Q

HbS polymerizes in the oxygenated or deoxygenated state?

A

Deoxygenated.

High metabolic activity lowers peripheral tissue pH and thus favors deoxygenation and then polymerization of a2BSBS

Polymerization requires homozygous HbS (aka no Sickle Trait)

35
Q

What prevents irreversible fiber formation & sickling in SCD?

A

Delay in polymerization allows HbS to return to the lungs to get O2

36
Q

Balanced polymorphism

A

condition where mutation leads to an advantage for the heterozygote but a disadvantage for the homozygote

ex: malaria resistance in Sickle Cell Trait

37
Q

Major mediators of epigenetic effects

A

DNA methylation, chromatin modifications, non-coding RNAs

38
Q

What maintains X inactivation?

A

DNA methylation

39
Q

Sickle Cell Disease

A

Group of inherited blood disorders:

  1. Hb SS (sickle cell anemia)
  2. Hb S/B thalassemia
  3. Hb SC
40
Q

Enzymes NEVER (even when mutated)

A

alter the reaction equilibrium constant

41
Q

CFTR

A

Cystic Fibrosis Transmembrane-conductance Regulator

Phenylalanine deletion at position 508 found in 90% of CF patients

Protein fails to fold and cannot reach membrane

42
Q

Hb genes are clustered on which chromosome?

A

16

43
Q

Ways to biochemically confirm clinical indications of SCD

A
  1. Gel electrophoresis of an Hb sample
  2. High-performance liquid chromatography of alpha and beta chains
  3. Treat RBCs with dithionite to rapidly deoxygenate & then observe rate of sickling under a microscope
44
Q

Fragile X Repeat

A

CGG

45
Q

Myotonic Dystrophy Repeat

A

CTG

46
Q

Huntington’s Disease Repeat

A

CAG

47
Q

C9ORF72/ALS/FTD Repeat

A

G4C2 or C4G2

48
Q

Is BRCA1/BRCA2 primarily germline or somatic mutation?

A

Germline

49
Q

Family history questions for cancer screening

A

Cancer (age of onset, type, pathology), genetic testing, surgeries (breast, ovaries)

50
Q

Where is genetics testing criteria found?

A

NCCN.org

51
Q

What is the most common form of breast and ovarian cancer?

A

Sporadic

52
Q

Genetic basis of Alveolar Capillary Dysplasia (ACD)

A

30-40% of cases due to mutation in the FOXF1 gene

Remaining cases have unknown cause

10% of cases have a familial association (usually siblings)

53
Q

Alveolar Capillary Dysplasia

A

developmental anomaly of the pulmonary vasculature; “misalignment” of the pulmonary veins

54
Q

Drapetomania

A

“disease” that caused slaves to run away from their masters

55
Q

Buck vs. Bell

A

Supreme Court allowed Virginia’s involuntary steriliaztion law to stand

56
Q

RNAi

A

RNA Interference

Technique to decrease mRNA levels of a target gene

siRNAs can be used to knockdown gene function

can have “off site” problems

57
Q

miRNAs

A

non-coding, transcribed genes

mutations of miRNAs can lead to cancer & other diseases

mutations that create (or abolish) an miRNA binding site can cause disease (like TS)

possible targets for gene therapy

58
Q

Benefits of RNAi

A
  1. very useful for studying gene function
  2. gene therapy
  3. fight off infection
  4. A number of products in clinical trials
59
Q

miRNA pathway leads to

A

Imperfect match with mRNA and thus protein synthesis inhibition

60
Q

RNAi pathway leads to

A

siRNA, perfect match with mRNA, and transcript degradation

61
Q

Different between RNAi and miRNA?

A

RNAi is a lab technique. miRNA is encoded in our genes

62
Q

Difference between RNAi and miRNA?

A

RNAi is a lab technique. miRNA is encoded in our genes

63
Q

Can miRNA cause disease?

A

Yes!

Ex: Random point mutation results in the production of a novel miRNA binding site (Tourette’s Syndrome)

Only happens if the miRNA is expressed in the tissue where the protein is

64
Q

myostatin

A

protein family that inhibits muscle differentiation and growth

elevated levels = little muscle growth
low levels = high muscle growth

65
Q

Problems with RNAi therapy

A
  1. Delivery - getting it where you want it
  2. Off-target effects (sequence homologies can affect this)
  3. May induce subsets of genes in the immune response
66
Q

Inheritance pattern of Fragile X

A

X-linked dominant

67
Q

Inheritance pattern of Huntington’s Disease

A

Autosomal Dominant

68
Q

Inheritance pattern of Myotonic Dystrophy

A

Autosomal Dominant

69
Q

Lifespan of sickle RBC

A

10 - 20 days

120 is normal

70
Q

What is the most common genetic disorder in the US?

A

Sickle Cell Disease

71
Q

The sigmoidal curve of O2 binding to Hb is best explained by what?

A

Positive cooperatively - an increase in the availability of binding sites.

72
Q

Majority of patients with ACD will have what other associated anomalies?

A

cardiovascular, gastrointestinal, urogenital, or musculoskeletal

73
Q

Five major models that researchers use to explain racial inequalities in health

A
  1. socioeconomic status
  2. health behaviors
  3. psychosocial stress
  4. social structure and cultural context
  5. genetics factors contribute substantially to racial inequalities in health
74
Q

Bio-psychosocial model

A

social and cultural factors have biological impacts beyond molecular genetic variation

75
Q

Familial Pleuropulmonary Blastoma

A

rare pediatric lung tumor that is part of an inherited cancer syndrome (germline mutation in DICER1 halts miRNA creation and thus creates serious issues)

MS1 Fall (23 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions