Brainscape's Knowledge GenomeTM

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


See full index

Unit 2 M2M > Unit 2 Day 8 > Flashcards

Unit 2 Day 8 Flashcards

1
Q

genetic testing definition

A
  • analyzing an individual’s genetic material to determine predisposition to particular conditions or to confirm diagnosis
  • risk or diagnosis*
  • examine blood/fluid/tissue for markers (biochemical, chromosomal, genetic) that indicate presence/absence of disease
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

loose definition of genetic testing

A

tests informing risks/diagnosis of genetic disease

  • genetic tests are not solely restricted to DNA basis*
  • other tests can diagnose genetic conditions*
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

what is chromosomal analysis useful for?

A
  • identifying aneuploidies (trisomy 21)
  • identifying large chromosomal structural changes (duplication, deletion, rearrangements)
  • 3-5 mb
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

WAGR syndrome

A
  • high resolution chromosmal analysis
  • wilims tumor, aniridia, genitourinary malformation, retardation
  • on 11p13, must be 3-5 mb or larger
  • find w/ PAX6 locus in FISH
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Fish analysis

A
  • specific, cost efficient if know/strongly suspect the diagnosis
  • micro-dup/del syndromes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what test do you use when you don’t know the diagnosis?

A

a “genomic” test

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

CMA-chromosomal microarray analysis

A
  • test and reference DNA sample targets
  • labeled w/ diff colors and washed across array covered in probes
  • abnormal ratios indicate deletions/duplications
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

microarray/aCGH

A
  • array comparative genomic hybridization
  • looks for deletions, shows them in same location
  • can compare sizes of similar deletions to see which zone is the critical disease region
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

dna sequencing

A
  • mutations in known genes, polymorphic variants, small (1-100nt) deletion/insertions
  • looks at sequence of known disease gene
  • DETECTS NOVEL MUTATIONS
  • may miss larger deletions
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

diagnostic testing

A
  • patient with signs/symptoms of disease

- positive genetic test result confirms diagnosis

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

predictive testing

A
  • patient with no signs/symptoms of genetic disease

- positive genetic provides estimate of future disease risk

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

allelic heterogeneity

A

different mutations (alleles) at a single locus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

genetic heterogeneity

A

different mutations (alleles) at different loci

  • SC: 1 mutation, 1 gene
  • CF: many mutations, 1 gene
  • AD: many genes/mutations
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

informativity as a concept when genetic test is normal

A
  • some negative results are truly negative

- other negative results are non-informative (do not exclude diagnosis/risk)

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

OTC Deficiency

A
  • X linked disease
  • Urea cycle defect
  • designed for healthy OTC patients, Jessie Gelsinger enrolled for therapy
  • adenoviral vector + otc gene used
  • he died after large dose of intra-hepatic drugs (treatment may have tempered if they had looked at bloodwork)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

chromosomal mutation challenges

A
  • cannot remove, silence, regulate extra chromosomal material
  • cannot insert missing material
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

single gene mutation challenges

A
  • cannot remove, silence, or regulate single genes

- cannot insert single genes

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

complex (genes+environment) mutation challenges

A
  • cannot remove, silence, or regulate multiple genes
  • cannot insert multiple genes
  • gene environment interactions not fully understood
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

genetic approach to human diseases

A
  • general management
  • primary disease specific therapies (if they exist)
  • genetic counseling
  • secondary prevention
  • primary prevention
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

therapies for metabolic disorders

A
  • usually due to enzyme deficiency
  • some can do dietary/pharmacological intervention
  • newborn screening, early diagnosis, treatment (less morbidity)
21
Q

treatment strategies for metabolic disorders

A
  • avoidance
  • dietary restriction (PKU)
  • replacement
  • diversion
  • inhibition
  • depletion
22
Q

protein replacement approaches

A
  • Alpha-1 AT: autosomal recessive, deficient, elastases unchecked, treat w/ recombinant AT1 therapy
  • Fabry: x linked, deficient in alpha-galactosidase a, treat with recombinant Alpha-gal
23
Q

Fabry treatments

A
  • glucose injections
  • chaperone based therapies
  • enzyme replacement therapy
  • chaperone + enzyme
24
Q

challenges to protein-based therapies?

A

production, delivery, targeting, imm. reactions, cost

25
Q

gene therapy

A
  • intro of dan into human cells to treat disease
  • should cure/slow progression of disease
  • done with non-viral (naked DNA and liposomes), adenoviral (dna viruses), and retroviral (rna viruses)
  • includes in vivo and ex vivo strategies
26
Q

x linked disorders

A
  • mutations on x chromosomes
  • mostly affects males
  • no male to male transmission
27
Q

x linked recessive inheritance

A
  • phenotype expressed in all males who carry affected genotype
  • phenotype in homozygous females only
  • heterozygote females=carriers
28
Q

x linked dominant inheritance

A

-expressed male hemizygotes and female heterozygotes

29
Q

x linked dominant diseases

A 
Hypophosphatemic Rickets
Alports
Fragile X Syndrome
Charcot Marie Tooth 
Incontinentia Pigmenti
Rett Syndrome
Orofaciodigital Syndrome
Focal Dermal Hypoplasia
30
Q

hypophosphatemic rickets

A
  • 1/20000
  • short stature
  • bone deformity
  • mutation in PHEX regulates fibroblast growth factor
  • kidneys unable to reabsorb phosphate
31
Q

fragile X

A

-x linked, CGG repeats
-1/2500-4000 males; 1/7-8000 females
-most common cause inherited mental delay
-maternal transmission bias
-dysmorphic features, autistic, biting, aggression, etc.
-FMR1, FMRP, Xq27.3 mutation
-protein for normal cognitive development/female reproductive function
46-55 repeats is grey zone
56-200 is premutation
>200 full mutation

32
Q

rett syndrome

A
  • x linked dominant
  • 1/10000 females
  • 95% new mutation rate
  • abnormal movement/coordination, loss communication, failure to thrive, seizures
  • MECP2 mutation
  • Methyl Cpg bp, impt nerve cells
33
Q

x linked recessive disorders

A 
Lesch-Nyhan Syndrome
Dystrophinopathies
Hunter’s Disease
Menkes Disease
Glucose 6 phosphate dehydrogenase deficiency
Hemophilia A and B
Wiscott Aldrich Syndrome
Colorblindness
34
Q

lesch-nyhan syndrome

A
  • x linked recessive
  • 1/ 380000
  • neurological/behavioral abnormalities
  • uric acid overproduction
  • HPRT1 mutation (recycles purines)
35
Q

dystrophinopathies

A
  • x linked recessive
  • spectrum muscle disease
  • Duchenne and Becker Muscular Dystrophy
  • DMD mutation, dystrophin
  • Xp21-21.1 (largest human gene)
36
Q

duchenne musc. dystrophy

A
  • progressive muscular weakness
  • calf weakness
  • ck levels=10x
  • dead in 30’s, absence dystrophin
37
Q

Becker muscular dystrophy

A
  • progressive muscular weakness
  • ck levels=5x
  • later onset, dead 40’s
  • abnormal quantity/quality dystrophin
38
Q

hemophilia A

A
  • recessive
  • 1/4000
  • 10% female carriers affected
  • F8 mutation
  • Xq28
  • 50% caused by 22A inversion
39
Q

replicative segregation

A
  • at cell division, multiple copies of tDNA replicate and sort randomly among newly synthesized mitochondria
  • normal or mutated DNA
40
Q

Kearns-sayre

A
  • mitochondrial inheritance
  • 1-3/100000
  • somatic mutation
  • affects eyes, cardiac conduction, ataxia, deafness, kidney issues
  • deletion of mtDNA (removes 12 genes commonly)
41
Q

MELAS

A

-Mitochondrial encephalomyopathy
-1 in 300,000
-Low new mutation rate
-muscle weakness, seizures, stroke-like episodes, lactic acidosis
80% caused by mutation in MT-TL1

42
Q

MERRF

A

-mitochondrial
-Myoclonic epilepsy with ragged-red fibers
-1/400000
-low new mutation rate
-muscle symptoms, seizures, ataxia, dementia
mutations in MT-TK

43
Q

leber hereditary optic neuropathy

A
  • mitochondrial inheritance
  • 1/30-50000 europeans
  • vision loss
  • mutations in MT-ND genes
44
Q

achondroplasia

A
  • major features: prenatal, rhizomelic short stature, spinal cord compression, brainstem compression
  • 1/40000
  • beteen 3-7% die unexpectedly in 1st year
  • due to advanced paternal age
  • autosomal dominant
  • FGFR3 Gly380Arg substitution–>gain of function
  • spinal cord compression (and apnea) most feared complication
45
Q

nonsyndromic deafness

A
  • congenital deafness is commonly recessive form
  • progressive childhood deafness is the dominant form often
  • 3/4 of genetic are non syndromic. GJB2 mutations are most common mutation.
46
Q

syndromic deafness

A
  • systems outside of ears involved

- different combinations can indicate different diseases/syndromes

47
Q

GJB2 mutations

A
  • recessive inheritance for severe congenital
  • parents=carriers
  • LOF mutations
  • autosomal dominant progressive with childhood onset
  • genetic, autosomal recessive, non syndromic deafness due to this mutation=most common category of congenital deafness*
48
Q

FMR1 Gene

A
  • fragile X syndrome
  • haplotype effect, full triplet expansion
  • premutation vs. mutation
  • full mutations have absent/reduced FMRP protein
  • premuations are not hypermethylated, have increased FMRP RNA
  • fragile X triplet repeat is in 5’UTR region

Unit 2 M2M (8 decks)

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