Genetic Disorders I Flashcards
SNP
variation at single nucleotide
CNV
copy number variation
-large stretches of DNA that are repeated
genomics
study of all genes
epigenetics
heritable changes not caused by changes in sequence
proteomics
study of proteins expressed in cells
miRNAs
inhibit gene expression
Dicer
cuts pre-miRNA
RISC
RNA inducing silencing complex
-complexed with miRNA to decrease gene translation
siRNA
therapeutic
most common cause of genetic disorders
multigenic disorders
- caused by complex interactions of variant forms of genes
- polymorphisms
missense
mutation alters meaning of sequnence
conservative - causes little change with AA switch
nonconservative - very different AA switch
sickle mutation
glutamic acid to valine in beta-globin of Hg
-causes sickle cell anemia
nonsense
encodes a stop codon
frameshift
alter reading frame
trinucleotide repeat mutations
amplification of sequence of three nucleotides
fragile x syndrome
fragile x syndrome
trinucleotide repeat mutation
-familial mental retardation 1 (FMR1)
mendelian disorders
mutation in single gene
codominant
full expression of both alleles in heterozygote
CCR5
used by HIV to enter cell
genetic heterogeneity
multiple different mutations lead to same outcome
pleiotropism
multiple end effects of single mutant gene
incomplete penetrance
individuals with mutant gene do not show phenotype
variable expressivity
trait caused by mutant gene is expressed differently
sperm of old men
can get autosomal dominant mutations
autosomal dominant
often loss of function
- nonenzyme proteins
- structural proteins
marfan syndrome
autosomal dominant
-affect of skeletal system
ehlers-danlos syndrome
autosomal dominant
-affect skeletal system
famililal hypercholesterolemia
autosomal dominant
-mutation in LDL receptor
huntington disease
autosomal dominant
- gain of function
- huntingtin protein
- toxic to neurons
onset of dominant vs. recessive?
dominant later in life
recessive earlier in life
autosomal recessive
often enzymes affected
lysosomal storage diseases
autosomal recessive
glycogen storage disease
autosomal recessive
alkaptonuria
autosomal recessive
G6PD deficiency
X-linked
- predispose RBCs to hemolysis
- often in males
anemia with malaria medication
Vit-D rickets
X-linked dominant
alpha-1 antitrypsin deficiency
decreased alpha-1 antitrypsin
- missense mutation
- leads to decreased metabolism of neutrophil elastase
emphysema and liver disease
cystic fibrosis
genetic defect in chloride ion channels
marfan syndrome
disorder in CT elastin
- skeletal, ocular, cardivascular problems
- reduced elasticity
- autosomal dominant
defect in fibrillin 1 (FBN1)
fibrillin-1
mutated in marfan syndrome
clinical features of marfan
tall stature, long extremities long fingers and toes (arachnodactylyl) joint laxity long head (dolichocephaly) spinal deformities dislocated lenses (ectopia lentis) mitral valve prolapse striae skin
Dx:
-two out of four system involvement (cardiovascular, skeletal, ocular, cutaneous), with minor of one other
arachnodactylyl
long fingers and toes
-seen in marfans
ehler-danlos syndrome
defect in synthesis or structure of fibrillar collagen
-has 6 variants
fragile skin, hypermobile joints, rupture of colon and large arteries
mitral regurgitation
in marfan syndrome
lysyl hydroxylase
autosomal recessive mutation - cross-linking of collagen IV
-leads to kypohoscoliosis type of EDS
type VI
COL3S1
autosomal dominant mutation - collagen type III
-vascular type of EDS
type IV
COL1A1 and COL1A2
autosomal dominant mutation - defect in conversion of procollagen to collagen
in arthrochalasia type of EDS
type VIIa, b
COL5A1 and COL5A2
autosomal dominant mutation - collagen type V
classical type of EDS
type I and II
familial hypercholesterolemia
mutation in LDL receptor
-increases LDL in plasma
increased scavenger receptor cholesterol pathway
-xanthomas and premature atherosclerosis
cholesterol metabolism
VLDL released from liver
-cleaved at fat or muscle cells - become IDL
IDL circulate with B-100 and E apoproteins
- taken up by LDL receptor in liver
- some converted to LDL
LDL in plasma removed by
- liver
- scavenger receptor
LDL mechanism into liver
bind receptor taken in as coated pit fuse with lysosome enzyme degradation leaves lysosome - via NPC1 and NPC2
cholesterol feedback
supress cholesterol synthesis
activate esterification and storage of cholesterol
supress synthesis of LDL receptor
mutation in synthesis of LDL receptor
class I
mutation causing LDL receptor in ER
class II
mutation causing LDL receptor that can’t bind
class III
mutations causing LDL receptor that cannot form coated pits
class IV
mutations in LDL recycling
class V
classes of familial hypercholesterolemia
Class 1-5
1 - synthesis 2 - transport 3 - binding 4 - clustering 5 - recycling
