Lecture - Ch. 5 - Genetics Flashcards
1
Q
there are 3 categories of human genetic disorders, what are they?
A
1) mutation in a single gene with large effects (aka mendelian disorders)
2) chromosomal DOs: structural or numerical alterations in autosomes and sex chromosomes
3) complex multigenic DOs (aka polymorphisms)
2
Q
describe mendelian/ single gene mutations and give an example
A
- rare, high penetrance
- sickle cell anemia: strong selective forces maintain it in the population
3
Q
describe chromosomals DOs
A
uncommon, high penetrance
4
Q
what are examples of complex multigenic/ polymorphic DOs
A
atherosclerosis, diabetes, hypertension, autoimmune dzs, height and weight
5
Q
what are mutations?
A
permanent changes in the DNA
6
Q
what type of mutations give rise to inherited dzs?
A
germ cell mutations
7
Q
what type of mutations give rise to cancer and congenital malformations?
A
somatic cell mutations
8
Q
what is a missense mutation? give an example
A
alter meaning of sequence of protein encoded
eg: sickle cell: glutamic acid to valine in beta-globin chain of Hb
9
Q
what is a nonsense mutation?
give example
A
stop codon
- if it occurs in beta-globin chain = beta-not-thalassemia
10
Q
what are transcription factors to be aware of when it comes to mutations in noncoding regions
A
MYC, JUN, p53
11
Q
what happens if you get deletions or insertions of 3 base pairs?
A
reading frame is intact, you just get an abnormal protein
12
Q
what is a trinucleotide-repeat?
A
amplilification of a sequence of 3 nucleotides;
almost all contain G and C
13
Q
what is anticipation and what are some examples?
A
as genetic disorders are passed down to the next gen, the symptoms appear earlier and worsen in severity
eg: Huntingtons Disease, and myotonic dystrophy
14
Q
what type of alterations occur in Cystic fibrosis? ABO blood type? and Tay sachs?
A
CF: 3 base deletion
ABO: single base deletion (frameshift)
Tay Sachs: 4 base insertion (frameshift)
15
Q
what are Autosomal Dominant disorders to be aware of here?
A
nervous stystem: HD, neurofibromatosis, myotonic dystrophy
MSK: Marfan, EDS, and Osteogenesis imperfecta
Metabolic: Familial hypercholesteremia
16
Q
how are AD DOs manifested?
A
in heterozygous state
17
Q
where do new AD mutations come from?
A
seem to occur in germ cells of relatively older fathers
18
Q
what is familial hypercholesterolemia an example of?
A
loss-of-function mutation
19
Q
what is HD an example of?
A
gain of fx mutation
20
Q
what are the 2 main patters of diseases that are AD? what patterns would tell you its an AD disorder?
A
1) affects regulation of complex metabolic pathways, subject to feedback inhibition
2) key structural proteins: collagen cytoskeleton etc
21
Q
what is an example of an AD disease with a pattern of affected regulation of metabolic pathways?
A
Fam. Hypercholest.
- LDL receptor concentration decreases by 50% -> secondarily incr. cholesterol -> atherosclerosis in affected heterozygots
22
Q
what is an example of a key structural protein affected by AD?
A
osteogenesis imperfecta
23
Q
in regards to onset, what gives it away that its an AD?
A
age of onset is delayed In many conditions; sx appear in adulthood
24
Q
whats is the chance of an affected parents with an AD would pass it on?
A
50/50
25
Almost all inborn errors of metabolism are what?
AR
26
what are some examples of AR DOs?
CF; PKU
27
What if two parents who are carriers of AR disease have kids? whats their chance of passing it on?
1/4
50/50: carrier
1/4 unaffected
28
what are the 3 features of AR DOs?
1) parent is usually not affected
2) singlings have 1/4 chance of having the trait
3) if mutation is low frequency in general populations, consanguineous marriage increases the chances above 1/4
29
how do you differentiate AR from AD?
- expression of defect is more uniform
- complete penetrance
- onset is **early** In life
- new mutations are rarely detected clinically (takes several gens)
- **many mutations Involve ENZYMES** (Inborn **metabolic** errors) (enzyme may be normal but low in abundance, or defective)
30
what two bugs give you CF?
staphylococcus and psudomonas
31
what is the primary defect in CF?
abnormal function of an **epithelial chloride channel protein**
encoded by: **CFTR** gene
chromosome: **7q31.2**
32
what symptoms do you expect to see? clinically, what should you keep an eye out for?
chronic lung disease (in kids!), male infertility (top two)
- pancreatic insufficiency, steatorrhea, intestinal obstruction
- cirrhosis, malnutrition
33
whats the incidence of CF?
1/2500 libe births,
## Footnote
**most common lethal genetic disease In Caucasians (AR)**
34
What are CF heterozygote carriers prone to?
resp and pancreatic disease
35
if you kiss a baby with CF, what do they taste like?
salt
36
what are key clinical findings of CF?
**maconium Ileus**
male urogentical abnormalities; pseudomonas aeruginosa infections
37
if babies have a diaper with a smell described as musty or mousy odor, what do you suspect?
PKU (phenylketonuria)
38
whats the incidence for PKU?
1/10,000 live births; caucasians
39
what is PKU and what are the clinical findings?
AR, deficiency of phenylalanine hydroxylase (PAH) leading to hyperphenylalaninemia
- phenylalanine cant be converted to tyrosine
- tyrosine is a precursor for melanin
------
normal at birth
at 6 months, severe mental retardation
hypopigmentation of hair and skin
eczema
40
what is the tx for PKU?
Dietary restriction
41
name some X linked DOs
G6PD def.
Fragile X syndrome
42
what are some things about X linked DOs to be aware of?
- almost all men are recessive (located in male-specific region of Y)
- males, usually infertile
- all daugheters of affected male are carriers
- hetero female dont express full phenotypic change cuz they got a normal paired allele
43
when taking a family history of X linked DO case, what will stand out?
all males affected, and skips a generation
44
what can you suspect if you give your pt a drug, and they come back with some sort of hemolytic reaction?
suspect G6PD deficiency
## Footnote
**drug Induced hemolytic rxs**
45
Describe the pedigree of X linked recessive if an affected father links w a normal mom; or an affected mom linking with a normal dad
- affected dad, normal mom: sons are unaffected, daughters are carriers
- reverse: both son and daughter have 50/50 of being unaffected; affected son = 25%; daughter carrier = 25%
46
describe mitochondrial inheritance:
47
what are mendelian disorders?
- alterations to a single gene: leads to abnormal product, or decrease of a normal product
48
what are the 4 main catergories of mendelian DOs?
49
what are the consequences of a mutation in regards to an enzmye for Mendelian DOs?
decrease activity (abn fx) or decr. amount of NL enzyme
50
what are the 3 major consequences of having enzyme defects?
1) accumulation of substrate
2) decrease amount of end product
3) failure to inactivate a tissue damaging substrate
51
what is an example of #1)
galactosemia
- galactose-1-phosphate uridyltransferase defeciency
52
what is an example of decreased amount of end product?
- albinism: lack of tyrosinase leads to less melanin
**lesch-nyhan:** Incr. Intermediate product and their breakdown product Is toxic
53
what is an example of failure to inactivate a tissue-damaging substrate?
**alpha1- antitrypsin defect:**
- unable to inactivate **neutrophi** **elastase** In lung -\> **EMPHYSEMA**
54
what is the most common clinically significant mutation in regards to lung disease?
PiZ; homozygots for the PiZZ protein have alpha1-AT levels that are only 10% of normal
55
what are two examples of defects in receptors and transport systems?
1) **familial hypercholsterolemia:** decr. synthesis or decr in fx of **LDL receptor =** defective transport of LDL into cells = secondary incr in cholesterol synthesis
2) **CF:** chloride ion transport
56
what are some examples in alterations in structure, fxs or quantity of non-enzyme proteins?
sickle cell disease: globin structure defect
- thalassemias: globin GENE affects amount of globin chains made
57
what medication can surface as adverse reactions to drugs in regards to mendelian DOs?
primaquine (anti-malerial) -\> severe hemolytic anemia = G6PD def.
58
whats the genetic scoop on Marfan?
AD
* FBN1*, chr. 15Q21.1
* FABN2,* CHR. 5q23.31 (less common)
- defect in (extracell. glycoprotein) **fibrillin-1**
59
whats the marfan syndrome incidence?
1 in 5K
70-85% familial
60
what are the 2 fundamental mechanisms by which loss of fibillin leads to clinical findings?
1) **loss of structural support** (where microfibril is rich)
2) **excessive activation** of TGF-beta signaling
61
what are physical/ clinical findings of Marfan Syndrome?
- tall, exceptionally long extremeties
- "double jointed," thumb can be hyperextended to wrist
**ectopia lentis** (dislocation of lens)
**aortic dissection,** mitral valve prolapse
**cystic medial necrosis**
62
whats the scoop on Ehlers-Danlos syndromes?
EDS
- **defect in synthesis/structure of fibrillar collagen**
- skin is hyperextensible, joints are hypermobile
- extra stretchy skin, extremely fragile and vulnerable to trauma
**\*gaping defects**, caused by minor injury. surgery is difficult cuz they lack normal tensile strength
63
because EDS is a basic defect in connective tissue, whats serious internal complications can you expect?
- rupture of colon and large arteries (vascular EDS)
- rupture of cornea and retinal detachment (kyphoscholiosis EDS)
- and diaphragmatic hernia (Classic EDS)
64
what are the clinical findings of Classic EDS and its gene defects?
**COL5A1, COL5A2**
Skin and joint hypermobility, atrophic scars, easy bruises
65
what are the clinical findings and gene defects for vascular EDS?
COL3A1
- thin skin
- arterial or uterine rupture
- bruising
- small joint hyperextensibility
66
what are the clinical findings and gene defects for
kyphoscholiosis EDS?
**lysyl hydroxylase**
hypotonia, joint laxity, congenital scoliosis, ocular fragility
67
what should lead you to the suspicion of familial hypercholesterolemia?
MI before 20 yo
68
facts on familial hypercholesterolemia?
- receptor dz
- mutation in receptor for LDL
- **one of the most frequent mendelian DOs**
1/500 from birth have 2-3 fold Increase In cholesterol and dfvelope **tendinous xanthomas**
**-** Incr. cholesterol leads to premature atheroschlerosis leading to increased risk of MIs
69
what if someone is homozygous for FH?
5-6 times the plasma cholesterol
- skin xanthomas (as well as coronary and cerebral and vascular **atherosclerosis** at a young age; **MI BEFORE 20 yo**
70
what does the LDL receptor recognize? where does the LDL come from? explain that train
liver cell secretes VLDL (with ApoC, ApoB-100, ApoE) --\> lypolysis of VLDL --\> IDL with ApoE and ApoB-100 ---\> conversion of IDL to LDL (**with ApoB-100),**
## Footnote
**LDL RECEPTOR ON LIVER RECOGNIZES ApoB-100**
71
what happens in lysosomal storage Dzs?
catabolism of subsrates of the missing enzyme remains incomplete, leading to the accumulation within the lisosomes = **primary accumulation**
- lysosomes are also used for autophagy, so when THAT is the route that is taken, the impaired autophagy gives rise to **secondary accumulation** of **autophagic substrates**
72
what are the 3 approaches to treating lysosomal dzs?
1) enzyme replacement therapy
2) substrate reduction therapy
3) some random shit based on our understanding of the molecular basis of the deficient enzyme (not even mentioned)
73
what is the enzyme deficient and major accumulating metabolites for tay sachs disease?
enzyme: alpha-subunit of hexosaminidase
metabolite: G-M2 ganglioside
74
what is the defective enzyme and accumulated metabolite in Gaucher dzs?
glucocerebrosidase
- glucocerebroside
75
what is the defective enzyme and major accumulated metabolite in Niemann-Pick disase (type A and B)
sphingomyelinase
sphingomyelin
76
what is the defective enzyme and major accumulated metabolite in muchopolysaccharidoses (MPS): MPS I
AKA HURLER Dz
alpha-l-iduronidase
dermatan sulfate, heparan sulfate
77
what is the defective enzyme and major accumulated metabolite in MPS II
aka Hunter Dz
l-iduronosulfate sulfatase
dermatan sulfate, heparan sulfate
78
whats Tay Sachs aka
Gm2 gangliosidosis: hexosminidase alpha-subunit deficiency)
79
where does the tay sachs mutation occur?
alpha-subunit locus on **chromosome 15** --\> severe deficiency of **hexosaminidase A**
80
what is the incidence and clinical presentation for tay sachs?
- eastern european (**Ashkenazic Jews):** 1 In 30 carrier rate
- normal at birth; 6month = **motor and mental detrioriation**
- by 1-2 years: vegetative state; deathy by 2-3 yo
- **CHERRY RED SPOT IN MACULA**
81
where do you find accumulations of Gm2 ganglioside?
neurons, retina,
heart, spleen, liver
82
what are the cytoplasmic inclusions for tay sachs?
fat stains on oil red O
and Sudan black B are positive
83
describe the Niemann-Pick Dz, types A and B
- lysosomal acumulations of **sphingomyelin** due to Inherited def. of **sphingomyelinase**
84
what do you see in a histo slide of Niemann-Pick Dz?
foamy cytoplasm
85
what are the raw stats on niemman-pick dz/
ashkenazi jews
AR
chr- **11p15.4**
86
describe type A, B, C
A: **severe Infantile form, complete lack** of enzyme, missense mt; **extensive neuro**, sx by 6m, death before 3yo
B: No CNS involvenemt, reach adulthood
C: most common, ***NPC1***, progressive neuro damage, ataxia
87
if you see zebra bodies, what is it?
NP diease
88
what are some other clinical findings of NP dz?
- massive splenomegaly (10x normal weight)
- 33-50% have cherry red retinal spot
89
whats the scoop on Gaucher Dz?
- AR
- glucocerebrosidase mutation
- accum of **glucocerebroside In phagocytes**
- this accumulation leads to activation of macrophages -\> secrete **IL-1, IL-6, TNF**
90
what is the most common lysosomal storage disorder?
gaucher
91
what are the 3 types?
type I: **chronic**, 90% of cases, european jews, **NO CNS**
TII: ACUTE NEUROPATHIC; **Infantile cerebral pattern, early death, NOT JEWISH**
TIII: intermediate; **progressive CNS, begins in adolescence of early adulthood**
92
whats the morphology of Gaucher?
distended phagocytic cells = gaucher cells in liver, spleen, **bone marrrow** (bone erosion --\> **pathologic fx),** LN,
93
whats it look like under a scope?
crumpled tissue paper
94
what organ is enlarged in gaucher dz?
spllen, more than 10kg;
also, pancytopenia or thrombocytopenia
95
whats the defect in mucopolysaccharidoses?
def enzymes degrading glycosaminoglycans
96
whats some facts on MPS?
All of the syndromes are AR, except Hunter syndrome (X-linked recessive)
- coarse facial features, **clouding of the cornia**, joint stiffness, mentally retarded
97
facts on hurler:
MPS 1-H;
**normal at birth,** hepatosplenomegaly at 6-24 months, **death by 6-10 yo due to cardiovasc complications**
**\*\*corneal clouding; dwarfism**
98
facts on Hunters syndrome
MPS II; X-LINKED;
**NO CORNEAL CLOUDING** (mild clinical course)
99
where do you find the mucopolysaccharides in MPS?
what are common histo findings?
mononuclear phagocytic cells
balloon cells + zebra bodies
100
what is common to all MPS?
hepatosplenomegaly; (esp. coronary deposists); brain lesions
101
what is the COD for MPS?
myocardial infarction and cardiac decompensation
102
what is glycogenoses?
glycogen storage disease
103
what does glygenoses result in?
glycogen storage in the liver or muscle
104
what are the 3 types?
hepatic form: von Gierke
myopathic form: McArdle
Misc: Pompe Dz
105
for von gierke (type I) what enzyme is deficient, what can you expect to see in the clinic?
deficiency of: **glucose-6-phosphatase**
Increased glycogen storage in liver = **low blood glucose (hypoglycemia)**
**----**
**clinic: hyperlipidemia, hyperuricemia; convulsions; gout and skin xanthomas; bleeding tendency**
106
in Mc Ardle dz, what is the defective enzyme and major accumulated metabolite in ?
**muscle phosphorylase** deficiency
**no Incr. In blood lactate after exercise**
leads to muscle cramps and weakness after exercise
107
in Pompe Dz, what is the defective enzyme and major accumulated metabolite in?
**glucosidase (acid maltase)** deficiency
also, **lack of branching enzymes**
**early death**
**cardiomegaly**
108
what can be said about complex multigenetic disorders?
they are of **multifactorial inheritance** = Implies interaction of environmental influences with two or more genes
## Footnote
**most common genetic cause of congenital malformations**
109
what can you suspect from a cleft lip, cleft palate and neural tube defects?
there was a reduced intake of folic acid preconceptionally
110
what type of severity can you expect frmo multifactorial inheritance'?
variable expressivity
reduced penetrance of a single mutant gene
111
euploid
any exactl multiple of haploid number (23)
112
aneuploid; how do they occur?
NOT an exact multiple of 23
- nondisjunction: gametes have +/- 1 chromosome
- anaphase lag: one normal cell + one monosomy cell
113
when monosomy occurs, whats the fate?
monosome doesnt form
trisomies do happen tho
114
whats mosaicism?
mitotic errors; gives rise to two or more populations of cells with different chromosomal complements
115
where is mosaicism common?
sex chromosomes
116
whats a ring chromosome?
where breaks occur at both ends of chrmosomes and the ends **fuse**
117
whats inversion? what are the two examples?
- 2 breaks occur within a single chromosomes with reincorporation of the **Inverted** Intervening segment
**1) paracentric:** only one arm involved
**2) pericentric:** breaks are on opposite sides of the centromere
118
whats isochromosome?
on arm of the chromosome is lost, and the remaining arm duplicates
- **chromo has either 2 short arms or two long arms**
119
whats translocation?
segment of one chromosome is transferred to another one
120
whats balanced reciprocal translocation?
single breaks in each of 2 chromosomes; but NO LOSS OF MATERIAL
NORMAL PHENOTYPE
121
What is an example of a Robertsonian translocation?
Trisomy 21
122
what are the 2 physical give aways of trisomy 21?
slanted palpebral fissures
single palmar crease
123
what is the most common chromosomal disorder?
trisomy 21
124
what is the number one cause of mental retardation?
trisomy 21
125
what is the US incidence of trisomy 21?
1 in 700; 95% of affected individuals have trisomy 21, 47 chromosomes
126
what is the strongest influence on incidence for trisomy 21?
maternal age
127
what are the diagnostic clinical features of trisomy 21?
- flat facial profile
- oblique palpebral fissures
- epicanthic folds
----------
40% of pts have congenitcal heart disease (ASD and VSD); responsible for majority of deaths in infancy
128
what are they at risk of developing?
10 to 20 fold incr. risk of developing **acute leukemia**
129
what are the 3 trisomies?
down: tri 21
patau: tri 13 (1 in 15,000 births)
edwards: tri 18 ( 1 in 8K)
130
what is the DiGeorge syndrome chromosome that is deleted?
Ch. 22q11.2
1/4K births
131
what can you expect from DiGeorge syndrome?
- congenital heart defects
- abnormalities of the palate,
facial dysmorphisms
developmental delays
**T-cell Immunodeficiency (gets viral Infections) and hypocalcemia**
132
what clinical findings do you find with DiG synd.
**thymic hypoplasia = T-cell immunodef.**
**parathyroid hypoplasia = HYPOcalcemia, cardiac malformations**
**velocardiofacial syndrome: long face, narrow palpebral fissures, overfolded ear helix, pear shaped nose, cleft palate**
**CATCH 22**
133
whats worse, imabalances of sex chromosomes or autosomal imbalances?
sex chromosomes are better tolerated
134
what two factors are peculiar to the sex chromosomes?
lyonization (inactivation) of all but one X chromosome
- modest amount of genetic material carried by the Y chromosome
135
whats the Lyon hypothesis?
1) only one X chromosome is genetically active
2) other X undergoes **heteropyknosis,** rendered Inactive
3) inactivation occurs at random
4) inactivation of same X chromo persists in cells derived from each precursor cell
136
what is a Barr body?
inactive X can be seen in the interphase nucleus as a darkly staining small mass in contact with the nuclear membrane
137
what determines the presence of the male sex?
presence of a single Y
138
when are sex chromosomes usually detected?
at puberty; they are suble, and chronic problems related to sexual development and fertility
139
what increases your chances of mental retardation?
an incr in X chromosomes
140
what is the most common cause of hypogonadism in males?
klinefelter syndrome: 47, XXY
141
what is the indicence of KS?
1 in 660; usually not detected til puberty
142
what are people with klinefelter syndrome at an increased risk of getting?
type 2 diabetes and metabolic syndromes
- 50% of them have mitral valve prolapse
- osteoporosis
**lack of secondary male characteristics: deep voice, beard, and male distribution of pubic hair**
**20X incr risk of breast cancer; incr risk of lupus**
143
what else does klinfelter syndrom cause?
male infertility and reduced spermatogenesis
144
buzzword for Kleinfelter?
gynecomastia
145
buzzwords for Turner syndrome?
- webb neck
- broad chest with spaced nipples
**STREAK OVARIES**
146
What is the karyotype for Turner syndrome?
45, X
\*complete or partial monosomy of X chr; hypogonadism in phenotypic females
other karyotypes: 45, X/ 46, XX;
45,X/ 46, XY;
45,X / 47, XXX;
147
What is the most common sex chromosomal abn in females?
turner syndrome; 1/2,500 births
148
what is cystic hygroma?
infant with edema; swelling of the neck due to lymph statis; it subsides but leaves behind bilateral neck webbing
149
what is turner syndrome the single most important cause of?
primary amenorrhea (1/3 of the cases)
150
what are the clinical findings of turner syndrome?
- congential heart disease (25-50% of pts; coarctation of aorta)
- cardiovasc. abn. are most important cause of incr. mortality
- shortness of stature
- amenorrhea
- streak ovaries (atrophi ovaries = fibrous strands, devoid of ova and follicles)
- hypothyroidism
- glucose intolerance, obesity, and insulin resistance
151
true hermaphrodite vs pseudo
true: presence of both ovaries and testis
psudo:
- female pseudohermaphro: ovaries, but a dick
- male pseudoherm: testis, but a vagina
152
what are the 4 categories of single-gene disorders with nonclassical inheritance
- diseases causing **trinucleotide-repeat** mts
- dos caused by mutations in **mitochondrial** genes
- **genomic Imprinting**
**- gonadal mosaicism**
153
what is the repeated sequence in fragile X syndrome?
CGG
protein: FMRP
154
what is the repeat in HD?
CAG
- huntingtin
155
what can you expect from trinucleotide-repeat mutations
neuro disorders
156
what are the 3 general principles of trinucleotide-repeat mutations?
1) asscted with **expansion of a stretch of trinucl., usually include G and C**
2) shit depends on sex of transmitting parent
3) the unstable repeats cause disease (via 3 mechanisms)
157
what are the 3 mechanisms by which unstable repeats cause disease?
1) loss of fx
2) toxic gain of fx
3) toxic gain of fx mediated by mRNA
158
what is a morphologic hallmark of trinucleotide-repeats?
accumulation of aggregated mutant proteins in large intranuclear inclusion
159
fragile X syndrome
loss of fx
trainscriptional silencing
CGG triplet in UTR
160
fragile-X tremor ataxia
accumulation of toxic mRNA
- transcriptional dysregulation
CGG triplet in UTR
161
friedreich ataxia
loss of fx
transcriptional silencing
GAA triplet
intron
162
HD
toxic gain of fx
polyglutamine expansions with misfolding
CAG triplet in exon
163
what is the second most common genetic cause of mental retardation?
fragile X syndrome
164
where does the trinucleotide mutation occur in FXs?
FMR1
(familial mental retardation-1)
- normal pop: 6-55 repeats;
- affected pop: 200-4000 repeats
\*when FMR1 gene exceeds about 230 repeats, the DNA of that region becomes super methylated = silencing of the FMR protein
165
what is the incidence of Fragile X syndrome?
1 in 1550 men
1 in 8000 women
166
phenotype for fragile X syndrome
long face, large mandible
large ears,
macro-orchidism (affects more than 90% of males)
- hyperextensible joints
- high arched palate
- mitral valve prolapse
167
fragile X lazy slide
168
HD facts
- 15 years of life after dx
- AD disease
- dementia and progressive jerky movemnts
- *HTT* located on chromonome **4p16.3**
**anticipation**
169
affected mothers of mitochondrial diseases pass the mutations to who?
all their children
170
mitochondrial fathers pass mito mutations to who?
no one
171
what is LHON?
progressive bilateral loss of central vission; first noted between ages 15-35, leading to eventual blindness
172
whats heteroplasmy and threshold effecct?
tissues have both normal and mutatnt mtDNA
- minimum number of mutant mtDNA needed in cell to give rise to disease
173
what is genomic imprinting?
selective inactivation of either maternal or paternal allele
174
when and where does imprinting occur?
in ovum or sperm, before fertilization
175
what are the 3 mechanisms of genomic impriting?
1) **deletions:** 70% of cases: eg: **15q12**
2) **Uniparental disomy:** eg: **prader-willi syndrome**; they have two maternal copies of ch 15
3) **defective Imprinting:** 1-4% of prader-willi folks, the paternal chromo carries the maternal imprin
reverse is true for angelman syndrome
176
prader-willi syndrome
mental retardation
short statur
- hypotonia
profound hyperphagia
obesity
small hands and feet
hypogonadism
**deletions of 15 (q11.2;q13)**
177
angelman syndorme
same deletion but derived from mothers
- ataxic gait, seizures, happy puppets
178
what will deletion of maternal chromosome render? paternal?
angelman
prader
179
