What type of study is the most common type of genetic study?
candidate gene association study
What type of study is best for mendelian traits (uncommon alleles with strong effects)?
Genetic linkage
What types of study can discover new unknown genes?
Genetic linkage, GWAS
What happens to recombination if the loci are too close to eachother?
loci close = tight linkage = lower crossover freq = lower recombination
What happens to recombination if the loci are too far from eachother?
loci far= absent linkage = higher crossover freq = higher recombination
WAGR
caused by?
deletion in Pax6 locus on 11p13 Wilms tumor Aniridia Genital malform Retardation
What type of genetic test should be used for WAGR
chromosomal analysis
Chromosomal analysis can diagnose
aneuploidies,
chromosomal: deletions, duplications insertions, rearrangements
Chromosomal analysis cannot diagnose
simple gene deletions,
pt mut
nucleotide repeats
small: dup insertions, methylation
FISH probes cannot diagnose
- deletions, rearrangements not spec. tested for
- duplications
- pt mut
- small del
Microarray can diagnose:
aneuploids
UNBALANCED chromosomal rearrangements
ch del/dup >200kb
Microarray cannot diagnose:
del/dup <200kb
balanced ch rearrangements/translocations
DNA seq cannot diagnose
larger indels, rearrangements
What mode of inheritance is cystic fibrosis?
Autosomal recessive
Cystic fibrosis is genetically homogenous/heterogeneous
genetically homogeneous
shows allelic heterogeneity not genetic heterogeneity
genetic heterogeneity
multiple genes (when mutated) are associated with same phenotype
what mode of inheritance is hypertrophic cardiomyopathy
autosomal dominant
hypertrophic cardiomyopathy shows allelic/genetic heterogeneity
both
What cofactor would you give for homocystinuria patients
pyridoxine
Multiple endocrine neoplasia (MEN)
cause?
mode of inheritance?
RET mutation
autosomal dominant
What substance would you avoid for:
G6PD Deficiency
antimalarial drugs (avoidance) -you should avoid antimalarial drugs if you are G6PD deficient
What substance would you give for:
PKU
low phenylalanine diet
dietary restriction
What substance would you give for:
congenital hypothyroidism
thyroxine
replacement
What substance would you give for:
urea cycle deficiency
sodium benzoate
diversion
What substance would you give for:
hypercholesterolemia
statin drugs
(inhibition)
Or
LDL apheresis
(depletion)
Fabrys disease
caused by? results in?
deficiency in alpha-galactosidase
resulting in accumulation of glycosphingolipids
Fabrys disease
phenotype
belly button spots microvascular disease neuropathy nephropathy sweat gland damage
2 ways to treat Fabrys disease
recombinant enz replacement therapy: alpha-gal
or
chaperone based therapy
Mode of inheritance of Fabrys
x linked
Nonsyndromic deafness
caused by?
Mut in GJB2 gene (DFNB1) encoding connexin26
What fraction of deafness cases are due to congenital defects? How much of that is due to hereditary/genetic factors?
1/2, 3/4(nonsyndromic)
Deafness with retinitis pigmentosa indicates:
usher syndrome
Deafness with thyroid goiter indicates:
prendred
Deafness with sudden death indicates:
jervell and lange nielson (AR) syndrome
Deafness with white forelock indicates:
waardenburg
Deafness with 8th n schwannomas indicates:
neurofibromatosis type II
Premutation of CGG repeats indicates what?
- Fragile X associated tremor/ataxia syndrome
2. Premature ovarian failure
TNRs are hyper/hypomethylated
hypermethylated -> reduced/absent FMRP prot
Do premutations of CGG have hypermethylation present?
no. Not hypermethylated -> increased FMRP RNA!
What substance would you avoid for:
acute intermittent porphyria
barbiturates