Genetics Flashcards
Both alleles contribute to phenotype of heterozygote
Codominance
Phenotype varies among individuals with same genotype
Variable Expressivity
ex. NF1
Not all individuals with a mutant genotype show the mutant phenotype
Incomplete Penetrance
BRCA1 gene mutations don’t always cause breast or ovarian cancer
One gene contributes to multiple phenotypic effects
Pleiotropy
Increased severity or earlier onset of disease in succeeding generations
Anticipation (ex Huntington)
Loss of heterozygosity
develops a mutation in a tumor suppressor gene, the complementary allele must be deleted/mutated before cancer develops
Dominant Negative Mutation
a heterozygote produces a nonfunctional altered protein that also prevents the normal gene product from functioning
Linkage Disequilibrium
tendency for certain alleles at 2 linked loci to occur together more often than expected by chance
Somatic Mosaicism
mutation propagates through multiple tissues or organs
Gonadal Mosaicism
mutation only in egg or sperm cells
Arises from mitotic errors AFTER fertilization
mosaicism
McCune Albright Syndrome
Cafe-au-lait, early puberty, abnormal bones
if mosaic - survivable
if somatic - lethal
Mutations at different loci can produce a similar phenotype
Locus heterogeneity (Albinism)
Different mutations in the same locus produce SAME phenotype
Allelic heterogeneity (beta-thalassemia)
Heteroplasmy
both normal and mutated mtDNA
variable expression of mitochondrial inherited disease
Heterodisomy
meiosis I error
isodisomy
meiosis II error or postzygotic chromosomal duplication of one of a pair of chromosomes and loss of the other original pair
Hardy-Weinberg
p^2+ 2pq + q^2
2pq is frequency of heterozygosity
p^2 frequency of homozygosity for allele p
X-linked recessive dx in males in q and females is q^2
Assumption of Hardy-Weinberg
No mutation occurring at locus, natural selection is not occurring, completely random mating, no net migration
Gene from mom is normally silent and Paternal gene is deleted or mutated
Maternal Imprinting
Prader-Willi Syndrome
Gene from dad is normally silent and Maternal gene is deleted/mutated
Paternal Imprinting
Angelman Syndrome
Hyperphagia, obesity, intellectual disability, hypogonadism, and hyptonia
Prader-Willi Syndrome
Happy puppet
Angelman Syndrome, also gets seizures, ataxia and severe intellectual disability
transmitted through both parents
mothers transmit to 50% of daughters and sons
Fathers transmit to all daughters but no sons
X-linked dominant
Type of inheritance for Hypophosphatemic Rickets
X-linked Dominant
Hypophophatemic Rickets
vitamin D resistant rickets, increased phosphate wasting at proximal tubule
Ragged Red Fibers
Mitochondrial Myopathies
Cysts on both kidneys
Autosomal Dominant Polycystic Kidney Disease
PKD1
On chromosome 16, 85% for AD polycystic kidney disease
PKD2
On chromosome 4, 15% for AD polycystic kidney disease
Familial Adenomatous Polyposis
Autosomal dominant, chromosome 5 (APC gene)
Familial Hypercholesterolemia
Autosomal dominant, elevated LDL due to defective or absent LDL receptor tendon xanthomas (Achilles Tendon)
Hereditary Hemorrhagic Telangiectasia
telangiectasia, recurrent epistaxis, skin discolorations, AV malformations, GI bleeding, hematuria
Autosomal Dominant
Hereditary Spherocytosis
spectrin or ankyrin defect, autosomal dominant
hemolytic anemia, increase MCHC
osmotic fragility
Chromosome Huntington’s is on
Chromosome 4
cystic medial necrosis of aorta
Marfan Syndrome (autosomal dominant)
ret gene
MEN 2A and 2B
von Recklinghausen Disease
NF1, chromosome 17
Autosomal Dominant
Bilateral Acoustic Schwannomas and Juvenile Cataracts
Neurofibromatosis 2, Chromosome 22
Autosomal dominant
Cutaneous Neurofibromas
NF1
Meningiomas and epndymomas
NF2
Numerous benign hamartomas, multisystem involvement
Tuberous Sclerosis, Autosomal Dominant
Incomplete Penetrance
von Hippel-Lindau disease
deleted VHL, chromosome 3
Autosomal Dominant
retinal mulberry, rhabdomyoma, sub-ungual fibromas, ashened skin, hematuria
Tuberous Sclerosis
Chr 9 & 16
Autosomal Recessive Diseases
Albinism, ARPKD, CF, glycogen storage diseases, hemochromatosis, Kartagener, mucopolysaccharidoses (except hunter syndrome), PKU, sickle cell, aphingolipidoses (except Fabry), thalassemias, Wilson disease
Cystic Fibrosis
Chromosome 7, defect in CFTR
commonly Phe508
Increased Chloride in Sweat
Cystic Fibrosis
Tx for CF
N-acetylcysteine to loosen mucus plugs dornase alfa (DNAse) to clear leukocytic debris
X-linked disorders
Bruton agammaglobulinemia, Wiskott-Aldrich syn, Fabry, G6PD deficiency, Ocular Albinism, Lesch-Nyhan Syn, Duchenne and Beckers, Hunter, Hemophilia A and B, Ornitine Transcarbamylase deficiency
Gower Maneuver
Duchenne Muscle dystrophy, frameshift mutation
Common cause of death from Duchenne
Dilated Cardiomyopathy
Becker Muscular Dystrophy
X-linked point mutation in dystrophin gene
CTG trinucleotide repeat expansion in DMPK gene
Myotonic Type 1 Muscular Dystrophy
Muscle Wasting, Frontal Balding, Cataracts, Testicular Atrophy, Arrhythmia
Myotonic Type 1 Muscular Dystrophy
CGG trinucleotide repeat
Fragile X syndrome
methylation and expression of the FMR1 gene
Fragile X syndrome
Macroorchidism, mitral valve prolapse, long face with large jaw, large ears
Fragile X syndrome
GAA trinucleotide repeat
Friedriech Ataxia
CAG trinucleotide repeat
Huntington Disease
Brushfield Spots
Whites of the eye in Down’s
1st trimester: increase nuchal translucency and hypoplastic nasal bone, decreased serum PAPP-A, increase beta-hCG
Down
2nd trimester: decreased AFP, increase beta-hCG, decreased estriol, increase inhibin A
Down
1 cause of Down
meiotic nondisjunction of homologous chromosomes
Trisomy 18
Edwards Syndrome
prominent occiput, rocker-bottom feet, micrognathia, low set ears
Edwards Syndrome
Trisomy 13
Patau Syndrome
retarded, rocker-bottom feet, microphthalmia, microcephaly, cleft lip/palate
Polydactyly and holoprosencephaly
Patau Syndrome
Nonreciprocal Chromosomal Translocation
Robertsonian translocation
13, 14, 15, 21, and 22
occurs on long arms of 2 acrocentric chromosomes
microdeletion of short arm Chromosome 5
Cri-du-Chat
high pitched crying/mewing, VSD, dumb
Cri-du-Chat
Congenital microdeletioin of long arm chromosome 7
deleted elastin gene, Williams Syndrome
Elfin facies, dumb, hypercalcemia, well-developed verbal skills, extreme friendliness to strangers
Williams Syndrome
Velocardiofacial Syndrome
22q11 deletion (same as DIGeorge) palate, facial, and cardiac defects
DiGeorge Syndrome
22q11 deletion
thymic, parathyroid, and cardiac defects
Who sells the best cookies?
Girl Scouts!
