Lecture 3 - Genetic Disorders Potpourri Flashcards
alpha globin gene is on chromosome ____;
beta globin and gamma globin genes are on chromosome ____
16, `11
the _____ controls beta globin expression during development. prior to birth, the _____ globin gene is expressed. after birth. the ____ globin gene is expressed. disorders that effect beta globins present _____
locus control region (LCR);
gamma, beta;
post-natally (cuz not really expressed at birth)
sickle cell:
conversion of ____ to ____. inheritance?
glu–>val;
autosomal recessive
not bothering with the symptoms
beta thal:
_____ mutations in ___ ____ and promoter sequences = reduced levels of ____. heterozygotes get _____
point, splice sites; beta globin; thallasemia minor (typically mild anemia)
alpha thal:
due to ______, genetically.
reduced levels of _____.
gene deletions;
alpha globin
globin deletion can occur with _____, where homologous pairing and unequal crossover occurs
non-allelic homologous recombination (NAHR)
marfan syndrome:
FBN1 normally helps sequester ____ ____; decreased FBN1 leads to ____ _____ action/signalling.
marfan syndrome is due to _____ exacerbated by a _____ effect
inactive TGFbeta;
increased TGF-beta;
haploinsufficiency, dominant-negative
apparently helps explain pleiotropy
what drug has shown to prevent aortic-root enlargement in mice with marfan?
it is thought to ____ TGF-beta
losartan;
block
loeys-dietzy syndrome:
typically due to genes encoding _____. causes very early _____ and pregnancy-related complications (Similar to marfan)
TGFbeta;
arterial aneurysms
homocysteinuria:
inheritance = ?
classic form is due to _____ deficiency. increasing vitamin ___ can help treat this
all forms cause an increase in homocysteine, which is pro-thrombotic or anti-thrombotic?
autosomal recessive;
cystathionine synthase, B6;
pro-thrombotic–> thrombotic and heart prpbs
other effects of homoecysteinuria besides thromboembolism:
____ (bone thing), marfinoid habitus, _____ lens _____, kyphosis
osteoporosis,
downward lens dislocation
other forms of homocysteinuria:
____ synthase deficiency.
different forms causing same disease is an example of _____
methionine synthase;
locus heterogeneity
PKU:
inheritance?
classic form is due to decreased ____ ____. various mutations in this gene can cause this = example of ____ ___;
“malignant form” is due to decreased _____
autosomal recessive
phenylalanine hydroxylase;
allelic heterogeneity;
BH4 (ie due to dihydropteridine reductase deficiency)
PKU: high levels of Phe inhibit transport of _____ ____ amino acids across the BBB–>intellectual ___. also causes ___ Retardation, ____ body odor, ____ skin, seizures, eczema
large neutral; disability; growth; mousy; fair
PKU:
screening shows increased _____. screening should be done when?
phenyl ketones;
2-3 days after birth (at birth, infant reflects maternal blood levels)
PKU diet:
avoid phenylalanine containing foods, such as the artificial sweetener _____. with good diet, all symptoms are reversible other than _____. should diet diet within 4 weeks of age. what cofactor can be supplemented?
aspartame;
mental retardation;
BH4 (aka Kuvan)
maternal PKU = due to elevated Phe levels in _____;
causes ____ cephaly, mid ____ hypoplasia, mental retardation, heart probs
mom;
micro, facial;
can be due to mild hyperphenylalanemia
Malignant PKU:
better or worse prognosis with treatment than classic PKU?
why?
worse;
BH4 is required for synthesis of other NTs
classic galactosemia:
inheritance?
due to absence of _____.
symptoms develop when infant consumes _____
autosomal recessive;
Galactose 1-P uridyltransferase (GALT);
lactose (ie breast milk, formula)
classic galactosemia:
___megaly, jaundice, infantile ____, mental probs, _____ (infection)_
hepatomegaly, cataracts;
E. coli sepsis
galactokinase defiency:
inheritance?
generally, just causes _____.
autosomal recessive;
cataracts
epimerase defeciency = similar to galactokinase deficiency or GALT deficiency?
GALT deficiency
galactosemia screening tests:
testing for elevated blood galactose/Gal 1 P can be inaccurate due to ______
GALT measurements can be inaccurate due to _____
requirement for milk ingestion before test (otherwise false neg);
heat denaturation (false positive)
cystic fibrosis:
inheritance?
GI probs: causes pancreatic ____, malabsorption with _____, ____ in newborns, liver cirrhosis, pancreatitis
autosomal recessive;
steatorrhea;
meconium ileus
CF:
pulm things: recurrent infections, especially ____ in adults. chronic ____ and cough, can cause cor pulmonare
pseudomonas;
bronchiectasis
CF:
usually due to defect in CFTR gene on chromosome ____. typically a deletion of ____ which impairs _____
7;
Phe508, post-translational processing–>CFTR retained in rER
CF other mutations: \_\_\_\_\_ mutations (G542X, R553X) cause reduction in mRNA transcripts and absence of CFTR. \_\_\_\_ affects activation of CFTR and alters function. \_\_\_\_ is a potentiator thaCt has been approved for treatment of this
nonsense (ie nonsense mediated decay);
G551D; Ivacaftor
CFTR encodes for a ___ gated ___ channel.
mutation–> in the mucosa, ___ can’t exit, causing increased intracellular ___ and ____ –> thick mucus
ATP gated Cl channel;
Chloride, Na, H2O
CF:
in sweat glannd, _____ of ___ and ____ is impaired –> very ____ sweat
reabsorption,
Na, Cl;
salty
ie chloride sweat test
CF:
characterized by polymporphisms in intron ___ of CFTR. people with the ____T genotype produce less CFTR protein. in patients without CF, this genoytype causes increased risk of male ____ due to ______
8;
5T (vs normal 9T genotype);
infertility, agenesis of vas deferens (ie congenital absence of vas deferns)
newborn CF test:
elevated _____ _____
immunoreactive tyrpsinogen
tay-sachs disease:
deficiency of ____ –> accumulate ____;
inheritance?
more common in what population
Hexosaminidase A; GM2 ganglioside;
autosomal recessive;
ashkenazi jews
due to mutation of HexA alpha subunit
tay-sachs symptoms:
accumulation of GM2 ganglioside in _____ .
progressive _____, development delay. _____ spot on macula due to what?
lysosomes;
neurodegeneration;
cherry red, lipid accumulation
tay-sachs carrier testing:
complicated by existence of “_____ alleles”. use 2 _____ to identify these alleles
pseudodeficiency;
polymorphisms
familial hypercholesterolemia:
inheritance?
example of a _____ disorder;
typically due to absent or defective ______
Autosomal dominant;
incompletely dominant/semidominant (ie homozygous is worse than heterozygous);
LDL receptors
famial hypercholesterolemia:
characterized by accelerated _____;
tendon ____, corneal _____
atheroscelrosis (Early MI);
xanthomas, arcus;
familial h-cholesterolemia:
in addition to LDL receptor probs, can be due to loss of function of apopprotein ____ or gain of function of _____
B-100; PCSK9 protease (breaks down LDL receptors)
LDL receptor problems are an example of _____;
can occur due to non-allelic homologous recombination, aka _____ crossing over
haploinsufficiency;
unequal
Charcot-Marie-Tooth (CMT):
inheritance is usually ____;
due to ______ of PMP-22 aka due to ____ expression
autosomal dominant;
duplication, over-expression
(chrom 17, can be due to NAHR)
CMT:
characterized by ____ demyelination of ____ NS nerves.
segmental, peripheral
hemophilia A:
____ disrupts genes in 45% of cases. happens in ____ meosis and is a type of ______
inversion;
male, NAHR
a ____ ___ ____ is a DNA segment 1 kb or larger that is present at a variable number in comparison to reference genome;
copy number variant
hemochromatosis:
inheritance =
classic triad of ____, ____, _____ due to ____ overload
AR;
cirrhosis, DM, skin pigmentation;
iron
hemochromatosis:
mutation in ____ gene, usually due to a ____ to ____ mutation at the 282 position on chromosome _____.
HFE; cysteine to tyrosine;
6
Hemochromotosis:
_____ hepcidin = _____ ferritin = _____ iron
decreased, increased, increased
Alzheimers:
name 3 early onset AD genes
APP, presenilin 1, presenilin 2
Lesch-Nyhan syndrome:
inheritance =
due to absent ______, which converts hypoxanthine to ____ and _____ to GMP
X-linked recessive;
HGPRT;
IMP, guanine
remember HGPRT for lesch-nyan = H = G = P = R = T =
also ____ “Sand” in diapers
hyperuricemia gout "pissed off" (self mutilation) retardation (intellectual) dysTonia
orange
lesch-nyhan;
defective ____ salvage;
treat with _____
purine;
allopurinol
alpha 1 antitrypsin (A1AT) deficiency:
inheritance?
codominant (notes also say AR)
A1AT deficiency/phenotype:
PiM =
PiZZ =
PiMZ =
normal;
severe disease, early emphysema and jaundice;
high risk in smokers
adult form of PKD:
inheritance =
85% due to mutation in ____ gene on chromosome ___;
15% due to mutation in ____ gene on chromosome ____
AD
PKD1, 16;
PKD2, 4
in addition to cysts, ADPKD causes... \_\_\_\_\_ (CNS); \_\_\_\_\_ (valve thing); \_\_\_\_\_ (cardiovascular); \_\_\_\_\_ in liver
berry aneurysms;
MVP;
HTN;
benign cysts
PKD1 and 2 mutations = dsrupt ____ signalling –> abnormal _____ mediated proliferation of cystic cells. also due to ____ dysfunction
Ca;
cAMP;
ciliary
