Genetics Flashcards
Gene that encodes ATP-gated chloride channel that secretes Cl- in the lung, GI tract and sweat glands
mutation is misfolded protein that is retained in the RER
AR
CFTR Phe508 deletion Cl- > 60 mEq/L in sweat is diagnostic Newborn: meconium ileus deficiency: ADEK vitamins (pancreatic insuff)
truncated dystrophin protein
X-linked frameshift mutation
accelerated muscle breakdown with pelvic girdle weakness and superior progression
Pseudohypertrophy of calf muscle from fibrofatty replacement
Gower maneuver to aid standing
Cause of death: dilated cardiomyopathy
Duchenne muscular dystrophy Gene: DMD dystrophin connects actin to ECM Lab: Increased CPK & aldolase Dx: bx and Western blot
point mutation in dystrophin
onset in adolescence or early adulthood
Becker muscular dystrophy
muscle wasting, frontal balding, cataracts, testicular atrophy, arrhythmia
CTG repeat expansion of DMPK gene
myotonic dystrophy (type 1)
CGG trinucleotide repeat
altered expression of FMR1 gene due to methylation
X-linked defect
Genetic mental retardation
Post-pubertal enlarged testes, long face with large jaw, large everted ears, autism, mitral valve prolapse
Fragile X syndrome
Brushfield spots
ASD
intellectual disability, flat facies, prominent epicanthal fold, single palmar crease, gap between 1st and 2nd toes, duodenal atresia, increased risk of ALL, AML and Alzheimer disease
meiotic nondisjunction -> advanced maternal age
Trisomy 21
severe intellectual disability rocker bottom feet micrognathia low-set ears, prominent occiput clenched hands congenital heart disease death within 1 year
Trisomy 18 = Edwards syndrome
Lab: decreased PAPP-A, free beta-hCG in trimester
Quad screen: decreased AFP, beta-hCG, estriol, decreased normal inhibin A
severe intellectual disability rocker bottom feet microphthalmia microcephaly cleft lip/palate holoprosencephaly polydactyly congenital heart disease
Patau syndrome = trisomy 13
1st trimester screen: decreased free beta-hCG, PAPP-A,
increased nuchal translucency
occurs when long arms of 2 acrocentric chromosomes fuse at the centromere with loss of the 2 short arms
Robertsonian translocation
balanced = no problem
unbalance = miscarriage, stillbirth, chromosome imbalance
congenital microdeletion of short arm of chromosome 5
microcephaly
moderate to severe intellectual disability
high-pitched cry
epicanthal folds
VSD
Cri-du-chat syndrome
congenital deletion of long arm of chromosome 7 (includes elastin gene)
elfin facies, intellectual disability,
hypercalcemia** (increased sensitivity to Vit D)
extreme friendliness to strangers
cardiovascular problems
Williams syndrome
22q11 deletion syndromes
DiGeorge syndrome
Velocardiofacial syndrome
one gene contributes to multiple phenotypic effects
pleiotropy
tumor suppressor gene mutation that is expressed when complementary allele is deleted/mutated
loss of heterozygosity
This does not happen with oncogenes
nonfunctional altered protein prevents normal gene product from functioning
dominant negative mutation
both alleles contribute to the phenotype of the heterozygote
codominance
ex: blood groups; alpha1-antitrypsin deficiency
not all individual with a mutant genotype show the mutant phenotype
incomplete penetrance
mutations at different loci can produce a similar phenotype
locus heterogeneity
ex: albinism
different mutations at the same locus can produce a similar phenotype
allelic heterogeneity
ex: beta-thalassemia
presence of both normal and mutated mtDNA, resulting in variable expression in mitochondrial inherited disease
heteroplasmy
methylation of one allele makes it inactive
deletion of the active allele produces disease
imprinting
gene from dad is silent (imprinting); maternal gene deleted/mutated
inappropriate laughter, seizures, ataxia, severe intellectual disability
“happy puppet”
Angelman syndrome
Paternal imprinting
“Angel’s daddy is silent in church but laughs at inappropriate jokes”
gene from mom is silent; paternal gene is mutated/deleted
hyperphagia, obesity, intellectual disability,
hypogonadism, hypotonia
Prader-Willi
Maternal imprinting
“willi’s mama is silent when she’s overeating”
mnemonic for blotting procedures
SNoW DRP
Southern blot = DNA
Northern blot = RNA
Western blot = protein ex: HIV
blotting technique to identify DNA-binding proteins
Southwestern blot
often present with myopathy, lactic acidosis, & CNS disease
secondary to failure in oxidative phosphorylation
muscle bx: ragged red fibers
mitochondrial myopathies
AD
mutation in PKD1
polycystic kidney disease
AD
mutations of APC gene on chromosome 5
FAP
familial adenomatous polyposis
AD
mutation in fibrillin-1 gene
Marfan
CT disorder, pectus excavatum, aortic incompetence -> aneurysms, floppy mitral valve, subluxation of lenses
AD
mutation in NF1 gene on chromosome 17
neurofibromatosis type 1
AD
bilateral acoustic schwannomas, juvenile cataracts
mutation on chromosome 22 NF2
neurofibromatosis type 2
AD
numerous benign hamartomas
incomplete penetrance & variable expression
tuberous sclerosis
deletion of VHL gene on chromosome 3
development of multiple tumors
von Hippel-Lindau disease
AD
mutations of RET
familial tumors of endocrine glands
MEN2A & 2B
