Genetics Flashcards
CBAVD
(congenital bilateral absence of the vas deferens) is a/w what mutation
CFTR
cystic fibrosis
- acute hemolytic anemia in response to oxidant drugs
- X linked recessive d/o
G6PD deficiency
blotchy red muscle fibers on Gomori trichrome stain
mitochondrial myopathies
fibers are irregular shape and size on cross section ; “ragged red fibers” b/c of accumulation of abnml mitochondria under the sarcolemma
mitochondrial mypopathies (3)
MERRF: myoclonic epilepsy with ragged red fibers
Leber optic neuropathy (blindness)
MELAS (mitochondrial enceph with stroke-like episodes and lactic acidosis)
lyonization
x-inactivation
condensed heterochromatin: _____ DNA and ____ histones
methylated DNA
deacetylated histones
pleiotropy
1 gene –> many effects
maternal inheritance
variable phenotype
heteroplasmy
different amounts of mt mitochondria
3 mt sites for early-onset familial alzheimer disease (
- Ch 21: amyloid precursor protein (APP) gene
- Ch 14: presenilin 1
- Ch 1: presinillin 2
(all promote production a A beta-amyloid)
Late-onset Alzheimer disease allele
E4 allele of Apoliprotein E
ApoE4 may be involved in senile plaque formation
Hypertrophic cardiomyopathy
AD
beta-myosin heavy chain mt
Hemeatologic risks in down synd
Acute Lymphoblastic Leukemia
Acute Myelogenous Leukemia
1st and 2nd MCC of congenital mental retardation
- Downs
2. Fragile X
Fragile X genetics
X linked
CGG trinuc repeats
FMR-1 gene on long arm of X
when cultured in folate-def medium, area of incrased repeats does not stain and appears “broken”
tall stature
gynecomastia
small, firm testes
Klinefelter
XXY
renal mass
deletion on 3p
VHL
majority of nondisjunction events (for tri 21) occur….
meiosis 1
prominent occiput micrognathia small mouth low-set and malformed ears rocker-bottom feet
Tri 18
Edwards
clenched hands with index finger overriding the middle finger and fifth overriding the fourth
Tri 18
Edward
cleft lip and palate polydactyly microcephaly/holoprosencephaly rocker-bottom feet umbilical hernia cardiac defects renal defects
Tri 13
Patau
stillborn:
edematous hands and feet
cystic hygroma of the neck
coartation of the aorta
stillborn Turner
45, XO
stillborn: flat facial features excessive skin at nape of neck VSD duodenal atresia
Tri 21
Down
GI a/w Patau (tri 13)
abdominal wall defects - omphalocele or ubilical hernia
pyloric stenosis
Friedreich’s ataxia (genetics)
AR
Frataxin gene (ch 9) - codes for mitochondrial protein important in respiratory function and Fe homestasis
- GAA repeats disrupt trasncription
HIV gag
p24
p7
HIV env
gp120
gp41
HIV pol
reverse transcriptase
integrase
protease
HIV tat and rev genes
regulatory genes required for viral replication
Huntington mech
- AD
- CAG repeats in the huntingtin protein
- expansion of plygutamine region –> GAIN OF FUNCTION mt –> various transcription factors
- thought to be through transcriptional repression silencing
- histone deacetylation –> silencing genes necessary for neuronal survival
Fragile X mech
increased CGG trinuc repeats –> hypermethylation of cytosine bases –> gene inactivation
when does trinucleotide expansion occur
paternal transmission
during spermatogenesis
Auer rods (gene)
t(15,17)
AML
t(15,17)
- AML
- Auer rods
- retinoic acid receptor (17) onto promylelocytic leukemia gene
–> abnl retinoic acid receptr inhibits differentiation of myelobloasts and triggers acute promyelocytic leukemia
t(8,14)
Burkett lymphoma
c-myc (proto-onc) -ch8
next to Ig heavy chain
t(9,22)
abl (9 to 22)
bcr-abl
tyrosine kinase
“philadelphia chromosome”
chronic myelogenous leukemia
t(11,14)
activation of cyclin D
Mantle cell lymphoma
deletion of 13q
chronic lymphocytic leukemia (CLL)
t(14,18)
bcl-2 (14) and Ig heavy chain
90% of Follicular lymphoma
30% of Diffuse large B-cell lymphoma
infant "floppy" not feeding well mild jsundice enlarged tongue hypotonia constipation umbilical hernia
congenital hypothyroidsm
15 y/o gait instability frequent falls kyphoscoliosis pes cavus lower extremity ataxia impaired position/joint sense (inherited)
Friedreich ataxia
Friedreich ataxia - areas affected
posterior columns and spinocerebellar tracts of spinal cord
loss of larger sensory cells of dorsal root ganglia
Friedrich ataxia - common cause of death
hyerptrophic cardiomyopathy –> arrhythmias and CHF
bulbar dysfunction (unable to protect airway)
hypertrophic cardiomyopathy
diabetes mellitus
kyphoscoliosis
foot deformities
Freidreich ataxia
bilateral renal masses composed fo fat, smooth muscle, and blood vessels… a/w…
(renal angiomyolipomas)
a/w tuberous sclerosis
may also see:
brain hamartomas
ash-leaf spots
Tuberous sclerosis (gen)
AD
Tuberous sclerosis symp
- cortical tubers
- subependymal hamartomas in brain–> seizures, mental retardation
- cardiac rhabdomyomas
- facial angiofibromas
- ash-leaf patches
pigmented nodules of the iris
Lisch nodules
Neurofibromatosis type 1
cafe au lait spots
neurofibromatosis type 1
optic gliomas
neurofibromatosis type 1
bilateral acoustic neuromas
neurofibromatosis type 2
meningiomas, gliomas, ependymomas of the spinal cord
neurofibromatosis type 2
neurofibromas
neurofibromatosis type 1
cerebellar hemangioblastomoas
retinal hemangiomas
liver cysts
VHL
leptomeningieal capillary-venous malformation
Sturge-Weber
also port wine stain
multiple telangiectasias of the skin and mucosa –> recurrent epistaxis or GI bleeding (melena)
Osler-Rendu-Weber
hereditary hemorrhagic telangiectasia
location of tangles and plaques in Alzheimers
generally
INTRAcellular neurofibrillary tangles
EXTRAcellular A-beta-amyloid plaques
composition of intracellular neurofibrillary tangles in Alzheimers
tau protein:
a primary component of intracellular microtubules
what is the normal function of amyloid precursor protein (APP)
involved in synaptic formation and repair
which is more specific to alzheimer’s - tangles or plaques?
tangles
- only in Alzheimer’s dementia
(amyloid plaques may be present in other neurodegen d/o and normal adults)
tri 21 quad screen
low AFP
HIGH beta-hCG
low estriol
HIGH inhbin A
achondroplasia genetics
AD GAIN of function mt FGFR3 gene (fibroblast growth factor receptor 3)
85% sporadic mutation due to advanced paternal age
complete hydatidaform mole:
ploidy uterus size hCG levels tissue risk of malignancy
diploid
uterus -“size greater than dates”
hCG - extremely high
tissue - only trophoblast
Malignancy risk - 15-20%
partial hydatidiform mole
ploidy uterus size hCG levels tissue risk of malignancy
triploid
uterus - normal size
hCG - high normal
tissue - fetal parts present
malignancy risk - low (
location of promoters
25-70 bases upstream from the gene
maternal virulization during pregnancy and ambiguous XX genetalia
placental aromatase deficiency
5’ prime post trascriptional mod
5’ guanasine cap
5’ cap methylation
= 7-methyl-guanosine cap
order of post translational mod
hnRNA (pre mRNA) 1) 5'cap 2) Poly A tail Introns 3) intron removal
BRCA 1&2
- DNA repair genes
- Breast and ovarian cancer
- 2 hit LOF
APC/beta-catenin
-wnt signalling pathway
- colon cancer
- gastric cancer
- pancreatic cancer
- Familial adenomatous polyposis (Lynch?)
-2 hit LOF
TP53
-genomic stability
- most cancers
- Li-Fraumeni syndrome
- 2 hit LOF
RB
G1/S transition inhibitor
- retinoblastoma
- osteosarcoma
2 hit LOF
WT1
urogenital differentiation
- Wilms tumor
2 hit LOF
VHL
ubiquitin ligase component
- renal cell carcinoma
- Von Hippel-Lindau syndrome
2 hit LOF
order of enzymes in BASE excision repair
-glycosylase: recognize abnormal base and cleave from DNA molecule –> AP site (apurinic/apyrimidinic)
- endonuclease:
cleaves 5’ end of AP site - lyase or phosphodiesterase:
completes extraction of AP site by removing sugar-phosphate base - DNA polymerase
- ligase
DNA damage from dietary nitrites
deamination of
cytosine –> uracil adenine –>hyoxanthine
guanine –> xanthine
Genetics for MCC of hair loss
(androgenic alopecia)
polygenic
variable penetrance
genomic change due to 1 base pair deletion resulting in changed/ineffective protein
frameshift
vs nonsense, which is a substitution
neonate w/ lymphadema and cystic hygromas
turner (XO)
de novo partial deletion of chromosome 5
5p-
cri du chat
round face
catlike cry
microcephaly
round face
catlike cry
microcephaly
cri du chat
5p-
usually de novo
Kallmann genetics
mt in KAL-1 gene or
fibroblast growth factor receptor 1 gene
delayed puberty
absence or incomplete dev of secondary sex characteristics by:
14 in boys
12 in girls
first sign of putberty
boys - testicular enlargement
girls - breast enlargement
3 cytogenic abnormalities that produce Down Syndrome
- Tri 21 (95%)
- Unbalanced Robertsonian translocation (2-3%)
- Mosaicism
proteins that can bind DNA (examples)
- transcription factors
- steroids
- thyroid proteins
- vit D receptors
- retinoic acid receptors
(others)
MYC proteins
mammalian transcription factors
e.g. c-myc is overexpressed in Burkitt lymphoma
imprinting
methylation of cytosine residues
X linked lysosmal storage diseases
Fabry
Hunter
Lesch-Nyhan genetics
X-linked Recessive
deficiency of hyoxanthine phosporibosyltransferase
hyoxanthine–>IMP
guanine –> GMP
purine salvage
Leber hereditary optic neuropathy genetics
mitochondrial
Hemophilia B genetics
X-linked recessive
factor IX def
classical galactosemia genetics
AR
typical inheritance pattern for enzyme deficiencies
AR
typical inheritance pattern for defective non-catalytic proteins
AD
tall stature gyneocomastia azoospermia behavior problems intellectual disability
Klinefelter
recognize
UGA
UAA
UAG
releasing factors
Meyer-Rokitascky-Kuster-Hauser (MRKH) syndrome
mullerian aplasia/vaginal agenesis
- no upper vagina
- variable uterine development
- normal ovaries
- normal dev of secondary sexual characteristics
- primary amenorrhea
- 50% of any mullerian defects (e.g. unicornate, bicornate, septate uterus) a/w urologic anomalies
(e. g. renal agenesis)
co-infection results in progeny that contain nucleocapsid from one strain and genome of the other;
next generation revert to original, unmixed
phenotype mixing
uptake of naked DNA
transformation
RAS
GTP binding protein
- cholangiocarcinoma
- pancreatic adenocarcinoma
1 hit GOF
MYC
transcription factor
- Burkitt lymphoma
1 hit GOF
ERBB1 (EGFR)
receptor tyrosine kinase
- lung adenocarcinoma
1 hit GOF
ERBB3 (HER2)
receptor tyrosine kinase
- breast cancer
1 hit GOF
ABL
nonreceptor tyrosine kinase
- chronic myelogenous leukemia (CML)
1 hit GOF
BRAF
RAS signal transduction
- hairy cell leukemia
- melenoma
1 hit GOF
