Genetics Flashcards
Meiosis I nondisjunction results in what?
failure of HOMOLOGOUS CHROMOSOMES to separate
after normal meiosis II with sister chromatid separation, 4 gametes form…
2 with 24 chromosomes (doubled chromosome is different due to sister chromatid sep > 2 bands on an RFLP analysis) > cause trisomies
2 with 22 chromosomes > cause monosomies
Meiosis II nondisjunction results in what?
failure of SISTER CHROMATIDS to separate
results in 2 gametes
1 with 24 chromosomes (double chromosome is SAME because sister chroms didnt sep > 1 thicker band on RFLP analysis) > causes trisomy
1 with 22 chroms > monosomy
MCC turner syndrome
less common causes + their consequence
Meiotic nondisjunction - forms a gamete without an X chromosome > all pts cells are 45, XO
(Early embryonic MITOTIC nondisjunction - mosaicism, some cells are 46, XX
may also be due to having both Xs but one is dysfunctional (ie “x fragments” or “isochromosomes”)
which gene is missing in Turner that results in short stature?
SHOX gene
promotes long bone growth
7 common conditions with polygenic inheritance
- Androgenetic Alopecia
- Hypertension
- Glaucoma
- Epilepsy
- Ischemic heart disease
- Schizophrenia
- Type II Diabetes
AH GEIST
Trisomy 18
name? cause? features?
(musculoskeletal features + organ systems affected; specific changes to organ systems in another card)
Edwards syndrome
meiotic nondisjunction of chr. 18 (incr. with maternal age)
Micrognathia Prominent occiput Low-set ears Clenched hands + overlapped fingers Rocker feet Limited hip abduction Overall growth restriction
Heart, renal + GI defects plus INTELLECTUAL disability
Trisomy 18 - Edward’s
Possible defect by organ system (3 systems, 5 defects)
Heart - VSD or PDA
GI - Meckel’s diverticulum or malrotation
Kidney - horseshoe
Cri du chat
genetics? s/s?
5p deletion
Cat-like cry
Hypotonia
Developmental delay / failure to thrive
Microcephaly
Low-set ears
Hypertelorism
Broad nasal bridge
Trisomy 13
name? externally visible defects + internal organ systems involved?
(Specific effects by organ system next)
Patau syndrome
MIDLINE DEFECTS:
Microcephaly / holoprosencephlay
Microphthalmia
Cleft lip/palate
Polydactyly
Rocker bottom feet
Cutis aplasia (scalp lesions)
Cardiac, renal and GI defects
Trisomy 13
effects by organ system?
Patau syndrome
GI - omphalocele, umbilical hernia
Heart - VSD, PDA
Urogenital - renal defects + abnormal genitals
Patau syndrome, trisomy 13
what general embryonic defect do most of the phenotypic features suggest?
a defect in PRECHORDAL MESODERM FUSION
affects midface, eyes, forebrain and GI (omphalocele)
Williams syndrome
4 features? 2 organs and 2 general features
elf-like face
extroverted
supravalvular AORTIC STENOSIS
RENAL ARTERY stenosis
(think open personality, closed arteries…)
DiGeorge
gene? msk / visible changes?
organ systems affected?
hypertelorism
micrognathia
cleft palate
CV - interrupted aortic arch, tet of Fallot
immune - thymic hypo-/aplasia
endocrine - hypoparathyroidism
Nucleotide Excision Repair
defective in what? enzyme sequence (3)?
defective in XERODERMA PIGMENTOSUM (XPA gene)
- ENDONUCLEASE - recognizes helix deformed by UV-induced thymine dimer; cleaves single strand on both sides of segment
- DNA POLYMERASE - replaces segment
- DNA LIGASE - seals gap
What is the formula for ALLELE FREQUENCY in Hardy-Weinberg analysis?
p + q = 1
p = normal allele freq q = mutant allele freq
What is the formula for PHENOTYPIC FREQUENCY in Hardy-Weinberg analysis?
p^2 + 2pq + q^2 = 1
p = normal allele freq q = mutant allele freq
With rare autosomal recessive disorders, what can we assume NORMAL ALLELE FREQUENCY to be?
(remember normal allele is known as “p” in Harvey Weinberg analysis)
1
because if the mutant allele frequency is 1/100… or 1/200… or less … then the normal allele frequency is 99/100 or higher and mathematically might as well be 100%
What is the formula for calculating MUTANT ALLELE FREQUENCY from disease prevalence in Harvey Weinberg analysis?
√q^2 = q
q = mutant allele frequency
diseases pts has 2 mutant alleles, so disease frequency = q^2
What is mosaicism?
Somatic vs. Gonadal/germline mosaicism?
presence of genetically distinct cell lines in same individual
somatic - mutation from mitotic errors AFTER FERTILIZATION and propagates through multiple tissues/organs
gonadal/germline - mutation ONLY IN EGG OR SPERM CELLS; if parent/relative does not have disease, can be suspected
What is an example of a disease with mosaicism?
think endocrine/dermatological
McCune Albright
altered G protein signaling > unilateral CALMs (large + ragged), polyostotic fibrous dysplasia, 1+ endocrinopathy (precocious pub)
lethal if mutation occurs before fertilization > all cells; survivable if mosaic
What hematological malignancy is most common in Downs’ syndrome?
what other one has increased risk?
ALL - acute lymphoblastic leukemia (10-20x risk)
AML also increased
what is the formula to find the FREQUENCY OF CARRIERS (heterozygotes) of the allele for a RARE AUTOSOMAL RECESSIVE disease?
freq. of carriers = 2q
because dominant allele frequency in rare AR diseases is assumed to be p = 1
so the normal 2pq formula for AR carriers becomes 2q
Williams syndrome
genetic abnormality? serum abnormality + why?
7q microdeletion - (includes elastin gene)
HYPERcalcemia due to increased vitamin D sensitivity
Syndrome with similar genetic defect to DiGeorge but without the hypocalcemia + thymic defect?
Velocardiofacial syndrome - 22q11 deletion
palate, facial and CV issues
(3rd/4th branchial pouches)
Uniparental Disomy
if pt is HETEROZYGOUS for the 2 chromosome copies inherited from 1 parent…. what is this called? and when did the error occur?
Heterodisomy
occurs in Meiosis I
(heterodisomy has one i > meiosis I)
Uniparental Disomy
if pt is HOMOZYGOUS for the 2 chromosome copies inherited from 1 parent…. what is this called? and when did the error occur?
Isodisomy
occurs in Meiosis II
(isodisomy has 2 “i”s > meiosis II)
How can a patient get an autosomal recessive disease WHEN ONLY ONE PATIENT IS A CARRIER?
uniparental disomy
specifically “isodisomy” where the pt is HOMOzygous for the 2 chromosome copies inherited from that parent (due to error in Meiosis II)
In Hardy Weinberg analysis…
what is the frequency of an XR disease in males? females?
(formulas)
in males frequency = q
(q is the frequency of the recessive allele)
in females frequency = q^2
(less frequent! because q is a fraction like… 1/1,000 so multiplying that by itself gives you 1/1,000,000)
Prader-Willi
genetics
(what is imprinted, what is deleted?)
Maternal genes are IMPRINTED and
Paternal deletion or mutation of chromosome 15
or
Maternal UPD of chr. 15 (25%)
(so remember the DELETION is what goes with the letter, the UPD/imprinting is what is opposite the letter… Prader = Paternal deletion, maternal UPD, imprinting)
Angelman syndrome
genetics
Paternal UBE3A (chr. 15) is imprinted and
Maternal allele is deleted or mutated
or
Paternal UPD (5%)
(AngelMan = Maternal deletion)
Angelman Syndrome
s/s (behavior, neuro issues)
- inappropriate laughter
- seizures
- ataxia
- severe retardation
