G&n Final - Week 1

Front 1

What are the three (3) major, related mechanisms of epigenetic inheritance?

Back 1

1. Covalent histone modification
2. DNA methylation/demethylation
3. Silencing/activation of chromatin

Front 2

What are the three (3) major inherited epigenetic diseases?

Back 2

1. Praeder-Willi syndrome
2. Angelman syndrome
3. Beckwith-Wiedmann syndrome

Front 3

T/F: Many cancer genes are incorrectly methylated/demethylated.

Back 3

True

Front 4

How does methylation silence genes?

Back 4

Attracts silencing complexes...

Regulatory proteins guide methyltransferases

Same regions attract proteins that confer transcriptional activity

Front 5

What is the 'nerdy' name for demethylation?

What are its two pathways?

Back 5

5mC erasure

1. Passive: 5mC -> 5hmC -> Cyt
2. Active: 5mC -> many intermediates (inc Thy) -> Cyt

Front 6

Define imprinting.

Back 6

Selective silencing of ONE parent's genes

Front 7

What is the #1 force holding together DNA?

Describe the other components as well.

Back 7

*Base stacking* (VdW, h-phobic interactions)
-Main free E store

Base pairing - minimal free E

Plectomeric coil into double helix (unwind, not pull - ladder)

Front 8

Describe the significance of the major/minor grooves.

Back 8

DNA recognition by proteins

Front 9

What are the three (3) physical factors of DNA stability and duplex formation?

Back 9

1. Tm (environment)
2. Base composition (exploited for probes)
3. Ionic strength

Front 10

What is Tm?

Back 10

Midpoint temperature where DNA is stable

Front 11

What are the three (3) major, related mechanisms of epigenetic inheritance?

Back 11

1. Covalent histone modification
2. DNA methylation/demethylation
3. Silencing/activation of chromatin

Front 12

What are the three (3) major inherited epigenetic diseases?

Back 12

1. Praeder-Willi syndrome
2. Angelman syndrome
3. Beckwith-Wiedmann syndrome

Front 13

T/F: Many cancer genes are incorrectly methylated/demethylated.

Back 13

True

Front 14

How does methylation silence genes?

Back 14

Attracts silencing complexes...

Regulatory proteins guide methyltransferases

Same regions attract proteins that confer transcriptional activity

Front 15

What is the 'nerdy' name for demethylation?

What are its two pathways?

Back 15

5mC erasure

1. Passive: 5mC -> 5hmC -> Cyt
2. Active: 5mC -> many intermediates (inc Thy) -> Cyt

Front 16

Define imprinting.

Back 16

Selective silencing of ONE parent's genes

Front 17

What is the #1 force holding together DNA?

Describe the other components as well.

Back 17

*Base stacking* (VdW, h-phobic interactions)
-Main free E store

Base pairing - minimal free E

Plectomeric coil into double helix (unwind, not pull - ladder)

Front 18

Describe the significance of the major/minor grooves.

Back 18

DNA recognition by proteins

Front 19

What are the three (3) physical factors of DNA stability and duplex formation?

Back 19

1. Tm (environment)
2. Base composition (exploited for probes)
3. Ionic strength

Front 20

What is Tm?

Back 20

Midpoint temperature where DNA is stable

Front 21

What effect does the addition of positive ions have on Tm?

Back 21

Decreased Tm because backbone (-) charges neutralized

Front 22

How can forensic scientists perform unambiguous DNA identification?

Back 22

PCR
Run PCR products on gel for VNTR's (hypervariable forensic sequences)
Compare VNTR configuration
18-20 genomic region

Front 23

What is the (+1) nucleotide?

Back 23

a) First nucleotide of RNA transcript
b) where transcription starts

Upstream: (-1), not 0

Front 24

"Write a sequence"

Back 24

All gene regulation signals: top (coding) [AUG, TATA, A2UA3]

Front 25

What is a gene?

Back 25

DNA segment coding a functional RNA transcript

coding RNA: mRNA -> ptn
ncRNA: many types

Front 26

What is a promoter?

Back 26

Txn start site - Guides RNAP

Front 27

What is a terminator?

Back 27

Txn stop site - Guides RNAP

Front 28

What is a start codon?

Back 28

AUG

Translation start in cytoplasm

Front 29

What are the three stop codon sequences? What are their functions?

Back 29

UAA/UAG/UGA

Translation stop (in cytoplasm)

Front 30

What is an ORF?

Back 30

Open reading frame

Front 31

What are RNA processing signals?

Back 31

Sites for intron splitting and polyadenylation

Front 32

What are the two (2) main mechanisms of mRNA processing?

Back 32

1. 5` cap addition
2. 3` Poly-A tail addition

Front 33

Describe 5` cap addition.

a) linkage
b) function
c) when added

Back 33

a) 5`-5` linkage

b)
Stability (protects 5` from ez's)
Transport (first to enter cytoplasm)
Translation (ribosome uses it to get onto mRNA)

c) Co-transcriptionally (requires Carboxyterminal domain [CTD] of Large RNAP

Front 34

True or false: Exon order is retained from DNA -> RNA?

Back 34

True

Front 35

Describe the translation process

Back 35

1. 40S SMALL subunit joins 5` cap
2. 40S continues down 5` -> 3` until AUG it "likes"
3. 60S joins 40S -> 80S
4. 80S goes 3nt at a time, inserts aa
5. 80S hits stop codon, complex dissociates

Front 36

True or false: the "stop" codon (UGA/UAG/UAA) codes for an amino acid.

Back 36

False

Front 37

True or false: Most disease-causing gene mutations are located in coding regions.

Back 37

False... promoter, exons, introns, UTR's

Front 38

What are the four specific types of mutations?

Back 38

1. Point mutation
-Missense
-Nonsense -> "nonsense-mediated decay"

2. Deletion/inversion/insertion
-Disrupt reading frame
-Usually premature stop -> truncated ptn

3. Expansions
EX: Huntingtons

4. Xsomal reciprocal/nonreciprocal translocations

Front 39

How can transcription be exploited to yield breast/colon cancer prognosis or diagnosis?

Back 39

Oncotype-DX: profiles mRNA in tumor cells

Front 40

Describe the three steps of transcription.

Back 40

1. Initiation
RNAP binds DNA
RNAP conformation change opens dsDNA in bubble

2. Elongation

3. Termination
RNAPII - preceded by poly-A cleavage
Releases small RNA fragment between cleavage and Poly-A

Front 41

What is the primary RNA polymerase of eukaryotes?

Back 41

II: mRNA, snRNA (splicing), miRNA

Front 42

What are the three components of the promoter region?

Back 42

1. Core promoter
2. Proximal control region
3. Distal control regions + Enhancers

Front 43

Describe the core promoter:
-Relationship to start site
-Regulatory regions
-"Other"

Back 43

Between 5` (-35) and 3` (+35) of start site

Regulatory regions: -3 to +5

Multiple conserved sequence elements

Front 44

Describe the multiple conserved sequence elements of the core promoter.

Back 44

Initiator region: -2 to +4
-In every promoter
-Can be 2+ (allows 2+ transcripts from one gene)

TATA box
-Binds TFIID, which allows RNAP "landing"
-Then, other factors solidify -> txn initiation

BRE/DPE

Front 45

What is the function/location of the proximal control region?

Back 45

Binds gene-specific transcription factors

-35 to -100

Front 46

What is the function/location of the distal control region + enhancers?

Back 46

Binds tissue-specific transcription factors

1000's of bp's away from start site

Front 47

What are the binding domains for gene-specific transcription factors and what are their functions?

Back 47

DBD- DNA binding domain
-Prox/dist to promoter

TAD - transactivation domain
-Interacts w/ basal txn apparatus via DNA looping (RNAP, mediator, TF)

DD - Dimerization domains
-Interacts w/ TF's - Homo/heterodimers

Front 48

Name the sites which activate core promoters 1000's of bp's away.

Back 48

Enhancer sites

Front 49

How does the enhancer binding protein work to initiate transcription?

Back 49

Binds TF, reaches out to general TF complex

Front 50

When does capping/splicing occur?

Back 50

Co-transcriptionally as RNA emerges from RNAP

Front 51

What allows TF's to recognize specific bp sequences?

Back 51

DNA binding and dimerization domains

Front 52

How do glucocorticoids (in ex) stimulate transcription?

Back 52

-Binds glucocorticoid receptor
-Binds GRE (glucocorticoid response element in promoter)
-Reaches out and touches basal cell transcription apparatus
-Has Zn fingers (get into DNA, look for specific seq in binding)

Front 53

What do TF's recognize?

Back 53

Patterns of H-bond donors/acceptors in major/minor grooves

Front 54

Describe the mutation in Duchenne muscular dystrophy.
-Gene
-Inheritance pattern
-Mutation mechanism

Back 54

Dystrophin gene (-> skeletal/cardiac muscle)
XR
Splice site mutations

Front 55

What are the differences between Duchenne v. Becker muscular dystrophies? What do they share?

Back 55

Duchenne

Mxn: COMPLETE elimination
-Nonsense (early stop), frameshift, splicing, large deletion

Sy: EARLY onset, more severe

Prog: Nonambulatory by teens, early death

----------
Becker

Mxn: PARTIALLY defective
-Point mxn, in-frame deletion (still make ptn, larger), rearrangements, deletions

Sy: LATER onset, slow progression

Prog: Nonambulatory in 20's live til 30's-50's

---------------

Both: Cause of death = dilated cardiomyopathy

Front 56

How do you determine the exact nature of a genetic defect?

Back 56

Multiplex PCR: across all introns/exons
-Use all primers
-Generate PCR products from all regions, find missing ones

Front 57

What are the six (6) mechanisms that can produce multiple proteins from the same gene?

Back 57

1. Alternate transcription start sites (promoters)
2. ** Alternative splicing (70% all genes)
3. Alternative use of tln start/stop codons
4. "Slippery regions" change frame
5. Alternative Poly-A (extra exons)
6. Post-translational processing -> breakdown into smaller peptides

Front 58

What are the three critical regions for splice signals of mRNA introns, which are highly-conserved?

Back 58

1. 5` splice junction
[E1] AG | GU [INTRON]

2. 3` splice junction
[INTRON] AG | G [E2]

3. UACUAAC box
In intron, contains "branch point A"

Front 59

Describe the process of mRNA splicing.

Back 59

-Cut @ 5` splice, 3` splice
-Lariat intermediate (loop w/ A branch point)
-Intron spliced out (spliceosome [snRNP's]
-Exon ligation

Front 60

What components make up the spliceosome?

Back 60

snRNP's:

U1 - 5` splice junction
U2 - A branch point
U4/5/6 - Knock off U1

Front 61

What is the purpose of the long nose of RNAPII? (3)

Back 61

1. Landing site: Poly A, splicing/capping factors

2. Allows orderly, sequential splicing

3. Splicing factors there, ready to jump on splice sites and begin splicing DURING transcription

Front 62

Describe how the two (2) tissue-specific regulatory proteins control use of splice sites, independent of transcription.

Back 62

1. Repressors: negative control, no splicing
2. Activators: positive control, splicing

Front 63

True or false: the First and Last exon HAVE to be exons in alternative splicing.

Back 63

True. There cannot be introns at 5` or 3` end.

Front 64

What is the modified scanning hypothesis?

Back 64

40S subunit stops at first AUG it "likes"

Front 65

What are the 2 pathways for mRNA degradation?

Back 65

1. Decay pathways
2. Regulation pathways

Front 66

What is the Decay pathway of mRNA degradation?

Back 66

Degrade from 3` UTR and 5` end

Front 67

What is the regulation pathway of mRNA degradation?

Back 67

NLS: Nuclear localization signal
-Binds adaptors for nuclear import
-Block: prevents protein influx for translation

Front 68

What are the three (3) trisomy disorders from Week 1?

Back 68

1. Trisomy 21 (Down's)
2. Trisomy 18 (Edwards)
3. Trisomy 13 (Patau)

Front 69

What are the manifestations of Edwards syndrome (trisomy 18)?

Back 69

"Fawn-like ears"
Clenched hand, returns if pulled out

Genital hypoplasia
Foot missing digits
Short sternum
Cardiac/renal defects
Facies

Front 70

What are the manifestations of Patau syndrome (trisomy 13)?

Back 70

"Rocker bottom" feet
Holoprosencephaly
Micropthalmia

Cleft
Polydactyly
Cryptorchidism
Cardiac defect

Front 71

What is the common cause of triploidy?

What is the most common triploid karyotype?

Back 71

Dispermy (2 sperm fertilize egg)

69, XXX (usu extra maternal Xsomes)

Front 72

What are the four (micro)deletion deletion syndromes we discussed in Week 1?

Back 72

1. 5p Syndrome (cri-du-chat)
2. Williams syndrome (elf)
3. DiGeorge/VCF
4. WAGR syndrome

Front 73

What is the deletion in cri-du-chat syndrome?

Back 73

5p

Front 74

What are the manifestations of 5p deletion?

Back 74

Cri-du-chat cry
Single palmar creases

Front 75

What is the deletion of Williams syndrome?

Back 75

Elastin on X7

2 common deletions, spontaneous

Front 76

What are the manifestations of Williams syndrome?

Back 76

Elf....
Triangular face
Small
Outgoing/happy
Hypercalcemia
MR

Front 77

What is the deletion of DiGeorge/Velocardiofacial syndrome?

What is the common cause?

Back 77

22q11.2 - TBX1 gene

Bad recombination of LCR's (low copy repeats)

Front 78

What are the manifestations of DiGeorge/Velocardiofacial syndrome?

Back 78

Facial dysmorphology (cleft)
Thymus deficiency
VSep defects
Slow growth

Front 79

What is the deletion in WAGR syndrome? What genes are affected?

Back 79

11p13

PAX6: Eye (aniridia)
WT1: Tsg, kidney/male genitals

Front 80

What are the clinical manifestations of WAGR syndrome?

Back 80

Aniridia - blindness/glaucoma
Kidney dysfunction
Undescended testes / small phallus
Wilms tumor

Front 81

What are the 4 sex chromosomal disorders we discussed during Week 1?

Back 81

1. Klinefelter's (extra X('s))
2. Extra Y
3. Turner's syndrome (X absence)
4. SRY deletion/crossover

Front 82

What are the two common Klinefelter karyotypes?

Back 82

47, XXY
48, XXXY

Front 83

What are the clinical manifestations of Klinefelter's syndrome in:
-47, XXY
-48, XXXY (severe)

Back 83

47,XXY
-Small testes, tall/thin
-Gynecomastia
-Hypogenitalism/azospermia

48, XXXY - Severe
-Genu valgum (knock kneed)
-Short stature
-Motor delay
-MR

Front 84

What is the most common "NOS" (extra Y karyotype)?

Back 84

47, XYY

Front 85

What are the manifestations of 47, XYY?

Back 85

No phenotype, normal fertility

Conduct disorder, LD's

Bite knuckles

Front 86

What are the 4 variants of Turner's syndrome karyotypes?

Back 86

1. 45, X
2. Mosaic (may include Y)
3. X-deletions
4. Deletions/rings/isochromes

Front 87

What are the manifestations of Turner's syndrome in:
-newborn
-adolescent

Back 87

Newborn:
-Web neck / space suit edema
-Aortic coarctation

Adolescent:
-Lack of puberty
-Short

Front 88

What are the manifestations of SRY deletion/crossover?

Back 88

No ovarian maintenance
Streak gonads

Front 89

What is the inheritance pattern of retinoblastoma?

Back 89

AD

Front 90

T/F: Retinoblastoma is a "2-hit" disease (i.e. before problems)

Back 90

True

Front 91

What is the inheritance pattern of neurofibromatosis?

Back 91

AD

Front 92

What are the manifestations of neurofibromatosis?

Back 92

Cafe-au-lait spots
Lisch nodules in eye

Front 93

What gene is deleted in Marfan syndrome?

Back 93

FBN1 (fibrillin protein)

Front 94

What is the inheritance pattern of Marfan syndrome?

Back 94

AD

Front 95

What are the diagnostic criteria for Marfan syndrome?

Back 95

Pectus carinatum/excavatum
Dec upper/lower body size
Whirl/thumb signs
Reduced elbow extension

Front 96

What are the manifestations of Marfan syndrome?

Back 96

"Spider fingers"
Ectopia lentis (vision impairment)
Dilated aortic root
Skeletal dysmorphia

Front 97

What are the five biochemical laboratory tests Heidenreich discussed?

Back 97

1. AA quant (Phe in blood)
2. Urine OA (methylmalonic acid)
3. Carnitine / acylcarnitine analysis: FA oxidation
4. Ammonia/BUN: Urea cycle defects
5. Urine mucopolysaccharides / VLCFA's: Zellwegger syndrome

Front 98

What is the main AA metabolism disorder?

Back 98

PKU

Front 99

What is the problem in PKU?

Back 99

-Can't metabolize Phe, accumulates
-Essential - can't synthesize
-Eat excess -> tyrosine (catabolic)

Front 100

What are the manifestations of PKU?

Back 100

Dev delay @ 3-4 months if untreated

Born normal - Mom "takes care of Phe"

Seizures, autistic features

Front 101

What is the mechanism of PKU?

Back 101

SEE PICTURE

Front 102

What is the tx for PKU?

Back 102

Low-protein diet

Can improve neurological f(x)

Front 103

What is the main organic acid metabolism disorder?

Back 103

Methylmalonic aciduria

Front 104

What is the problem in methylmalonic aciduria?

Back 104

Can't convert methylmalonyl-CoA into succinyl-CoA (for Kreb's)

-Lack of methylmalonyl-CoA mutase

MMA produced in many catabolic reactions (aa's, chol, odd-chain FA's)

Front 105

What is the manifestation of methylmalonic aciduria?

Back 105

Week 1 - Severe acidosis

Front 106

What is the tx for methylmalonic aciduria?

Back 106

Low protein diet

Liver transplant to prevent acidotic episodes later in life

Potential bone marrow

Front 107

What is the mechanism of methylmalonic aciduria?

Back 107

SEE PICTURE

Front 108

What is the main peroxisomal disorder?

Back 108

Zellwegger syndrome

Front 109

What is the inheritance pattern of metabolic disorders (except Zellwegger)?

Back 109

AD

Front 110

What is the problem in Zellwegger Syndrome?

Back 110

Can't form peroxisomes

Front 111

What are the manifestations of Zellwegger syndrome?

Back 111

Large head
Flat nasal bridge
Hypotonia

Front 112

How is Zellwegger syndrome diagnosed?

Back 112

Biochemical test: Inc VLCFA, abnormal bile acid

Prenatal dx

Front 113

What is the tx for Zellwegger syndrome?

Back 113

None effective

Front 114

What are the three lysosomal storage diseases Heidenreich discussed?

Back 114

1. Tay-Sach's
2. Gaucher's
3. Hurlers/(Hunters?) syndrome

Front 115

What is the problem in Hurler's syndrome?

Back 115

Can't metabolize mucopolysacharrides (MPS)
-MPS's compose ground substance b/w collagen + fibrinogen of skin
-During growth, MPS's accumulate -> dysmorphia

Front 116

What is the presentation of Hurler's syndrome?

Back 116

Macrocephaly
Upturned nose / flat nasal bridge
Short
Hepatosplenomegaly

Front 117

What treatment is available for Hurler's syndrome?

Back 117

Enzyme replacement (aldurazyme)

-Weekly infusion into blood stream (not BB barrier)
-Ports into ventricles -> directly infuse brain w/ enzyme

Front 118

What is the mineral disorder Heidenreich discussed?

Back 118

Menke's disease

Front 119

What is the problem in Menke's disease?

Back 119

Can't absorb Cu2+ across intestinal epi -> severe deficiency

Front 120

What is the inheritance pattern of Menke's disease?

Back 120

XR (mostly males)

In females...
-Consanguinity
-Turner's
-X translocation, autosomal comes back to X
-Skewed inactivation

Front 121

What is the manifestation of Menke's disease?

Back 121

"Kinky hair"
Neurodegeneration

Front 122

What is the tx of Menke's disease?

Back 122

Copper histidinate infusion under investigation

Front 123

What is the vitamin disorder Heidenreich discussed?

Back 123

Biotinidase deficiency

Front 124

What is the problem in biotinidase deficiency?

Back 124

Biotinidase defect: Can't recycle/reclaim biotin

F(x): performs -COOH reactions

Front 125

What is the manifestation of biotinidase deficiency?

Back 125

Alopecia
Dermatitis
Deafness
Seizures / neurodeterioration @ 4-6 months

Front 126

What is the mechanism of biotinidase deficiency?

Back 126

SEE PICTURE

Front 127

What is the treatment for biotinidase deficiency?

Back 127

Biotin supplementation -> cure

Front 128

What are the three main FA oxidation disorders we discussed in class?

Back 128

1. MCAD (most common, AR)
2. FAD
3. "Rest" (VLCAD, often cardiac/hepatic pblms)

Front 129

What is the problem in MCAD?

Back 129

Deficiency: medium chain acyl-CoA dehydrogenase deficiency

Front 130

What is the manifestation of MCAD?

Back 130

-Lethargy/vomiting child after fasting

-Hypoketotic hypoglycemia

-Possibly asymptomatic

Front 131

What is the tx for MCAD deficiency?

Back 131

Avoidance of fasting (cake frosting)

Rapid tx of hypoglycemia

Front 132

What is the purine/pyrimidine disorder Heidenreich talked about?

Back 132

Lesch-Nyhan

Front 133

What is the problem in Lesch-Nyhan syndrome?

Back 133

HGPRT mutation - purine reclamation

Front 134

What is the inheritance pattern in Lesch-Nyhan syndrome?

Back 134

XR (males)

Front 135

What is the manifestation of Lesch-Nyhan syndrome?

Back 135

Neurological dysfunction [basal ganglia disorders]
Self-mutilation
Inc uric acid -> gout

Front 136

What is the tx for Lesch-Nyhan syndrome?

Back 136

Low purine diet
Allopurinol
Medications for neurologic signs

Front 137

What is the carbohydrate disorder Heidenreich talked about?

Back 137

hereditary fructose intolerance

Front 138

What is the problem in hereditary fructose intolerance?

Back 138

Aldolase B (fructoaldolase) defect

Normal: Converts fructose to glucose

So, nursing babies get no fructose

Front 139

What is the manifestation of hereditary fructose intolerance?

Back 139

Acute ingestion: vomiting/hypoglycemia

Chronic ingestion: hepatomegaly / renal dysfunction

Front 140

What is the mechanism of hereditary fructose intolerance?

Back 140

SEE PICTURE

Front 141

How is hereditary fructose intolerance diagnosed?

Back 141

Apple juice -> "Boom! Coma"

Molecular analysis of fructoaldolase

Front 142

What is the tx for hereditary fructose intolerance?

Back 142

Restrict fruit/veg/corn syrup/table sugar

Front 143

What is the problem in a urea cycle defect?

Back 143

Ammonia buildup... can't convert ammonia to urea

Front 144

What is the most common ez deficiency in urea cycle defect?

Back 144

OTC (ornithine transcarbamylase)

Also:
NAGS, CPS, ASA, As, Arginase

Front 145

What are the manifestations of a urea cycle defect?

Back 145

Presents as severe hyperammonemia
Neuro damage if no rapid tx

Front 146

What is the mechanism of a urea cycle defect?

Back 146

SEE PICTURE

Front 147

How is a urea cycle defect diagnosed?

Back 147

BUN
Inc ammonia, diag aa

Front 148

What is the tx for a urea cycle defect?

Back 148

Dialysis in babies
Dietary restiction (low protein)
Ammonia scavenger medications

Pxl liver transplant - lots of urea cycle in liver

Front 149

What is the difference between sex-limited, -influenced, and -linked?

Back 149

Sex-limited: only expressed in one sex

Sex-influenced: influenced by sex hormones (i.e. male pattern baldness)

Front 150

What is male hemizygosity?

Back 150

Males express all X genes

Front 151

What is X inactivation? (aka Lyonization)

Back 151

Inactivation event - "dosage compensation" (dec expression to 1 allele)

Front 152

What is the pseudoautosomal region?

Back 152

X&Y have "Par" @ talomeres

-Crossing over here b/w X&Y
-Stays active w/ X inactivation

Front 153

What is the name of the inactivated X chrosome?

Back 153

Barr body

Front 154

Describe hypohidrotic ectodermal dysplasia.
-Inheritance
-Manifestation (female/male)

Back 154

X-linked

Female: missing teeth / anhydrosis patches

Male: no teeth, total agenesis, sparse hair

Front 155

What is the function of the SRY gene? What happens when it is absent?

Back 155

Testicular development

Female phenotype (XX,male) w/ ambiguous genitalia

Front 156

What genes allow spermatogenesis?

Back 156

Yq genes

Front 157

The inheritance pattern of sex-linked disorders is always ___ and usually ___.

Back 157

X-linked; recessive

Front 158

Why aren't Y-related disorders relevant?

Back 158

Would cause infertility -> mnot inherited

Front 159

What is the 1 dominant sex-linked disorder we talked about?

Back 159

Incontinentia pigmenti

Front 160

What are the 3 recessive sex-linked disorders we talked about?

Back 160

Duchenne
Hemophilia
Red/green colorblindnes

Front 161

What is the inheritance pattern of incontinentia pigmenti?

Back 161

Dominant sex-linked

Front 162

What is the genetic defect in incontinentia pigmenti?

Back 162

NEMO gene

Front 163

What are the manifestations of incontinentia pigmenti?

Back 163

Redness/blisters
Thick skin
Neurologically normal (i.e. not herpes)

Front 164

True or false: incontinentia pigmenti is only present in females.

Back 164

True

Front 165

What is the genetic defect in hemophilia?

Back 165

Reduced clotting factor 8(A) or 9(B)

Front 166

Why are the clinical manifestations of hemophilia so variable?

Back 166

Different mutations in same gene = allelic heterogeneity

Front 167

What is the inheritance pattern of hemophilia?

Back 167

X-linked recessive

Front 168

What is the genetic defect and mutation locus of Duchenne muscular dystrophy?

Back 168

Deletion/mxn of dystrophin gene @ Xp21

Front 169

What are the clinical manifestations of Duchenne muscular dystrophy?

Back 169

Normal @ birth -> muscle weakness -> wheelchair @ 10yo -> death

Pseudohypertrophy (Gower's sign)

Respiratory insufficiency

Front 170

What are the manifestations of Duchenne muscular dystrophy in a carrier female?

Back 170

None - asymptomatic