Genetics I Flashcards
codominance
both alleles contribute to phenotype
ABO blood group
variable expressivity
phenotype varies with same genotype
incomplete penetrance
not all individuals with mutant genotype show phenotype
pleiotrophy
one gene contributes multiple phenotypes
anticipation
increased severity and earlier onset disease over multi generations
loss of heterozygosity
two hit hypothesis
inherited mutation - tumor suppressor gene
complementary allele must be mutated as well
dominant negative mutation
heterozygote produces nonfunctional altered protein also prevents normal gene product from functioning
linkage disequilibrium
tendency certain alleles at 2 loci to occur together
more or less often than by chance alone
mosaicism
distinct cell line same individual
mccune albright syndrome
mutation GPCR
unilateral cafe-au-lait spots, polyostotic fibrous dysplasia, precocious puberty
survivable if patient has mosaicism
locus heterogeneity
mutation at different loci - similar phenotype
allelic heterogeneity
different mutation same loci - similar phenotype
heteroplasmy
variable expression of mitochondria inherited disease
both normal and mutated mito DNA present
uniparental disomy
2 copies chromosome 1 parent
no copies from other parent
individual is euploid - normal # chromosomes
heterodisomy - meiosis I error
isodisomy - meosis II error
hardy weinberg
p2 + 2pq + q2 = 1
p + q = 1
frequency X-linked recessive - males = q / female = q2
assumption hardy weinbery
no mutation
natural selection no occurring
random mating
no migration
prader willi and angelman syndrome
deletions chromosome 15
prader willi syndrome
maternal imprinting - inactivated
chromosome 15
gene mom normally silent
paternal gene deleted
hyperphagia, obesity, intellect disability, hypogonadism
angelman syndrome
paternal imprinting - inactivated
chromosome 15
gene dad normal silent
maternal gene deleted
inappropriate laughter, seizure, ataxia, intellect disability
imprinting
one allele inactivated - methylation
autosomal dominant
most generations
male and female affected
often structural gene defect
autosomal recessive
seen 1 generation only
often enzyme deficiency
X-linked recessive
son heterozygote mom - 50% chance affected
no male to male transmission
skips generations
X-linked dominant
father transmit to all daughter
mother transmit to 50% of daughter and sons
mitochondrial inheritance
transmitted only through mother
ex/ mito myopathy - ragged red fibers
auto dominant polycystic kidney disease
massive enlargement kidneys
mutation PKD1 - chromosome 16 - MC
or mutation PKD2 - chromosome 4
familial adenomatous polyposis
autosomal dominant
mutation chromosome 5q = APC gene
colon covered adenomatous polyps
familal hypercholesterolemia
autosomal dominant
defective LDL receptor
tendon xanthoma - achilles
hereditary hemorrhagic telangiectasia
autosomal dominant
disorder blood vessels
telangiectasia, recurrent epistaxis, skin discolorations
-arteriovenous malformation
osler weber rendu syndrome
hereditary hemorrhagic telangiectasia
hereditary spherocytosis
autosomal dominant
mutation spectrin or ankyrin RBCs
hemolytic anemia
increased MCHC and RDW
tx - splenectomy
tx hereditary spherocytosis
splenectomy
huntington disease
autosomal dominant
depression, dementia, chorea movement
trinucleotide CAG repeat - chromosome 4
anticipation
li-fraumeni syndrome
autosomal dominant
abnormal TP53
multi malignancy early age
SBLA cancer syndrome
-sarcoma, breast, leukemia, adrenal gland
marfan syndrome
autosomal dominant
chromosome 15 - mutation fibrin - scaffold for elastin
hypermobile joint, tall and skinny, subluxation of lens, aortic dissection
MEN
autosomal dominant
multiple endocrine neoplasias
-1, 2A, 2B
MEN1
MEN1 gene
MEN2
RET gene
NF1
von-recklinghausen disease
autosomal dominant
cafe au lait spots - cutaneous neurofibroma - optic glioma, pheochromocytoma, lisch nodule (iris hamartoma)
chromosome 17
NF2
autosomal dominant
chromosome 22
bilateral acoustic neuroma, juvenile cataract, meningioma, ependymoma
tuberous sclerosis
autosomal dominant
numerous benign hamartomas
von hippel lindau disease
autosomal dominant
deletion VHL - tumor suppressor
chromosome 3
develop numerous tumors
