Genetics Flashcards
variable expressivity
phenotype varies among individuals with the same genotype (different disease severity)
incomplete penetrance
not all individuals with a mutant gene show mutant phenotype
pleiotropy
one gene contributes to multiple phenotypic effects
mosaicism
presence of genetically distinct cell lines in the same individual, arises from mitotic errors after fertilization
heteroplasmy
presence of both normal and mutated mtDNA, resulting in variable expression of mitochondrial inherited disease
uniparental disomy
offspring gets 2 copies of a chromosome from 1 parent (heterodisomy is a meiosis 1 error, isodisomy is a meiosis II error)
imprinting
epigenetic process involving methylation - gene is silenced without a change in sequence
Prader-Willi syndrome
maternal imprinting: gene from mom is normally silent and Paternal gene is deleted/mutated
- leads to hyperphagia, obesity, intellectual disability, hypogonadism, and hypotonia
- Prader Willi is Paternal
Angelman syndrome
paternal imprinting: gene from dad is usually silent and Maternal gene is mutated/deleted
- inappropriate laughter, seizures, ataxia, and severe intellectual disability
- angelMan has Maternal mutation
Autosomal Dominant Polycystic Kidney Disease
- adult onset, autosomal dominant
- bilateral, massively enlarged kidneys due to large cysts
- 85% due to PKD1 mutation on Chromosome 16
FAP
- autosomal dominant
- APC gene mutation leading to multiple colonic polyps that will progress to cancer if colon is not removed
- on chromosome 5
hereditary hemorrhagic telangiectasia
- AD inherited disorder of blood vessels
- telangiectasias, recurrent epistaxis, skin discolorations, AVMs, GI bleeding, hematuria
- aka Osler-Weber-Rendu
Hungtington disease
- AD disease with CAG repeat on chromosome 4
- depression, progressive dementia, choreiform movements, caudate atrophy, decreased GABA and Ach
NF1
- AD disorder with 100% penetrance, variable expression
- mutation in NF1 gene on chromosome 17 leads to cafe-au-lait spots and cutaneous neurofibromas
NF2
- AD disorder with NF2 mutation on chromosome 22
- bilateral acoustic schwannomas, juvenile cataracts, meningiomas, and ependymomas
von Hippel-Lindau disease
- AD disorder with numerous benign and malignant tumors
- deletion of VHL gene (tumor suppressor) on chromosome 3
chromosome mutations of autosomal dominant disorders
3- VHL
4- huntington
5- FAP
16- ADPKD
17- NF1
22- NF2
Duchenne muscular dystrophy
- x linked frameshift mutation in dystrophin gene
- onset before 5 years, dilated cardiomyopathy
- increased CPK and aldolase
- confirm diagnosis with western blot and muscle biopsy
Becker muscular dystrophy
- point mutation in dystrophin gene
- adolescent onset, less severe than Duchenne
myotonic type 1 muscular dystrophy
- CTG trinucleotide repeat expansion in DMPK gene –> abnormal expression of myotin protein kinase –> myotonia, muscle wasting, frontal balding, cataracts, testicular atrophy and arrhythmia
Fragile X
- x linked defect affecting methylation and expression of FMR1 gene (CGG repeat)
- post-pubertal macroorchidism, long face with large jaw, large everted ears, autism, mitral valve prolapse
- Fragile X = Xtra large testes, jaw and ears
Autosomal trisomies
- Downs (21-Drinking age) - duodenal atresia, hirschsprung, ostium primum ASDs, increased bHCG
- Edwards (18-Election age) - low set Ears, prominent occiput, clenched hands, decreased bHCG
- Patau syndrome (13-Puberty) - microcephaly, cleft lip/palate, holoprosencephaly, polydactyly
- common to all - decreased PAPP-A, increased nuchal translucency, intellectual disability, congenital heart disease,
Robertsonian translocation
nonreciprocal chromosomal translocation that occurs when long arms of 2 acrocentric chromosomes fuse at the centromere and the 2 short arms are lost
Cru-du-chat syndrome
congenital microdeletion of 5p (short arm)
- microcephaly, mod-severe intellectual disability, high-pitched cry, epicanthal folds, VSD
Williams syndrome
congenital microdeletion of long arm of chromosome 7 (7q), which includes elastin gene
- distinctive “elfin” facies, intellectual disability, hypercalcemia, well developed verbal skills and friendliness with strangers, CV probs
22q11 deletion sydromes
CATCH-22
- Cleft palate, Abnormal facies, Thymic aplasia (T cell deficiency), Cardiac defects, Hypocalcemia 2/2 parathyroid aplasia
- Di George - thymic, parathyroid and cardiac defects
- Velocardiofacial syndrome - palate, facial and CV defects
