Exam 1- lectures 1 & 2 Flashcards
How much of the genome codes for proteins?
2%
how much of the genome is “junk DNA”?
50%
how much “difference” do we see in people?
0.1%
locus
the position of an allele on a chromosome
allele
a variant of a gene
central dogma
DNA->mRNA->protein
what DNA is inherited?
DNA in gametes
4 types of SNP mutations
silent, conservative missense, non-conservative missense, nonsense
conservative missense mutation
amino acids are similar and the protein function is similar
silent mutation
leads to the same amino acid
non-conservative mutation
amino acids are different, so chaped & function of protein will change
nonsense mutation
codes for a stop codon
most clinically impactful mutations
nonsense & non-conservative
incomplete dominance
both traits are expressed; blended-> pink
co-dominance
not blended; both expressed equally-> red & white spots
mendelial genetics
monogenic
quantitative traits
(expressivity) traits that vary in the extent to which they are expressed in each individual (i.e. height & weight)
incomplete penetrance
not every individual who has the genotype expresses the phenotype; other genes may affect the phenotype
multifactoral traits
both environment and genetic components (hemochromatosis)
genetic switching
fly eyes
after the genes have already been made, change due to environmental factor & new gene will be passed on to offspring
how many deleterious genes does each person carry?
estimated 5-8
pleiotropism
a mutation in a single gene can lead to many effects
genetic heterogeneity
mutations at several genetic loci may produce the same trait
huntington’s diease
autosomal dominant
triplet repeat on chromosome 4
dysfunctional protein builds up -> toxic GABA neurons
hyperkinesis, parkisonian rigidity, bradykinesia, death w/in 15 years
familial hypercholesterolemia
autosomal dominant
defective LDL receptor-> inability to bind LDL & transport
atheroscleosis, MI by 20 yo
autosomal dominant diseases
huntington’s disease
familial hypercholesterolemia
autosomeal recessive dieases
PKU,
cystic fibrosis
sickle cell anemia
phenylketonuria (PKU)
defective phenylalanine hydrocylase
phenylalanine is not catabolized-> build up in CNS-> severe mental retardation
cystic fibrosis
defective Cl ion channel-> thickened mucus secretions
resp. infections, pancreatic dysfunction, impaired male fertility
sickle cell anemia
defective HbS
sickling of RBCs-> blockage of blood vessels-> tissue hypoxia
x-linked recessive diseases affect who most?
males bc X is inherited from mother
x-linked recessive dseases
hemophilia A & B
GPPD deficiency
diabetes insipidus
hemophilia A & B
defect in clotting factors 8 & 9
-> prolonged bleeding due to inability to form a fibrin clot
G6PD deficiency
usually asymptomatic until triggered (drugs, infection, fava beans)-> RBC unable to repaid
diabetes insipidus
mutation in AVPR2 gene-> defective vasopressin receptor
what is the most common enzyme deficiency in humans?
G6PD
polygenic traits
height, intelligence, BP, skin color, metabolic parameters
polygenic continuous diseases
HTN, DM
polygenic congenital malformations
cleft lip & palate, pyloric stenosis, anencephaly, congenital heart disease
polygenic discontinuous diseases
manic-depressive psychosis, rheumatoid arthritis
diseases due to non-disjunction
down’s syndrome (trisomy 21)
turner’s syndrome (X0)
klinefeiter’s syndrome (XXY)
positive selection examples
alcohol tolerance lactose tolerance sickle cell anemia- heterozygous protects against malaria CF- protects against thyoid tay sachs- protects against TB type AB blood- resistant to cholera
gene-environment interaction examples
multiple sclerosis, asthma, factor V leiden & OCPs
multiple sclerosis
higher incidence far from equator (US, Canada, N. Europe)
increased risk of venous thrombosis in oral contraceptive users who are carriers of what mutation?
factor V leiden mutation
what is the most common cardiovascular event in young women?
venous thrombosis
factor V Leiden mutation
ARG replaced by GLN at 506
R506 is the cleavage site for aPC
R506Q is not cleaved, there fore factor V is not inactivated
overproduction of thrombin & fibrin-> excessive clotting
ACMG recommendations when to do genetic testing for Factor V Leiden mutation & OC use
-<50, MI and smoker
routine genetic screening
trisomy 21, trisomy 12, sick cell, GALT, CF, G6PD, PKU, Beta-thelassemia, etc
