Single Gene Disorders Flashcards
What is haploinsufficiency?
half of gene dosage may not be enough for cell to carry out functions
Would a disease on the Y chromosome be dominant or negative?
Dominant
What is the relationship of an X-linked disease regarding father to daughter transfer? Sons?
all daughters will have it
no sons will have it
What is penetrance?
genotype does not manifest as phenotype
What is expressivity?
how strong the phenotype manifests itself
What type of disease is Huntington’s?
Autosomal Dominant
What is the triplet repeat present in Huntingtons?
CAG
What amino acid does the triplet repeat code for? What is the end product?
glutamine
poly-glutamine
The severity and age of onset of HD depends on what?
extent of the triplet expansion
What kind of mutations takes place in achondroplasia?
dominant
What gene is affected in achondroplasia?
fibroblast growth factor receptor
What kind of receptor is the FGFR?
transmembrane tyrosine kinase
What is the function of the FGFR?
to inhibit chondrocyte proliferation
What do mutations in FGFR do?
constitutive expression of the receptor that inhibits bone growth
What is a mutation hotspot?
chromosomal region where mutations occur frequently
What is a typical chromosomal region for a mutation hotspot?
GC repeat
Dominant forms of EDS are caused by what?
mutations in collagen genes
Less severe forms of EDS are caused by what?
mutations in the genes for collagen processing
Familial Hypercholesterolemia is what kind of mutation?
autosomal dominant
The RET gene encodes what?
tyrosine kinase receptor
Loss of function of the RET gene causes what?
Hirschsprung Disease
Why does the loss of RET cause Hirschprung Disease?
impairs the ability of neural crest cells to populate the colon with ganglia
A gain of function mutation in the RET gene causes what?
Multiple Endocrine Neoplasia
Constitutive activation of the RET gene causes an increase in what cells?
Neuroendocrine Cells
Are mutations in the RET gene dominant or negative?
dominant
What are two hallmarks of an X-linked recessive disorder?
no father to son transmission
boys affected more than girls
What is the most common X-linked recessive disease?
Duchenne Muscular Dystrophy
What gene is affected in DMD?
dystrophin
What if the function of dystrophin?
attachment of cytoskeleton to ECM in muscle
What is more severe, DMD or Beckers Muscular Dystrophy?
DMD
Dystrophin is linked by what protein to the ECM?
beta-dystroglycan
What is a hallmark of X-linked dominant diseases?
father to daughter transmission
Mitochondrial genes affects what two types of tissues predominantly?
muscles and nerves
What is the mode of mitochondrial gene transmission?
mothers to all daughters
Mutations rates are higher where, mitochondria or nuclear genes?
mitochondrial
What is heteroplasmy?
presence of a mixture of more than one type of organeller genome
What is the most prevalent mitochondrial disorder?
Lebers Hereditary Optic Neuropathy
What gene is defective in LHON? What protein does this affect?
ND1
Complex I
Why can consanguineous matings be so detrimental?
closely related individuals often care the same mutant allele
What does the coefficient of inbreeding describe?
homozygosity of a child
What is an autosomal dominant disease with variable expressivity?
neurofibromatosis
The severity and age of onset of Huntingtons depend on what?
triplet expansion
What kind of mutation is present in achondroplasia? What receptor is affected?
dominant
fibroblast growth factor
What is a common mutation hotspot sequence?
CG dinucleotide repeat
Is EDS dominant, recessive or both?
both
Is osteogenesis imperfecta dominant or recessive?
dominant
The dominant negative effect often targets what types of proteins?
proteins in complexes
Is familial hypercholesterolemia dominant or recessive?
dominant
What is the RET gene product?
tyrosine kinase receptor
Loss of function of RET causes what disease?
Hirchsprung Disease
RET protein functions in the development of what type of cells?
neural crest cells
A gain of function in the RET gene causes what disease?
Multiple Endocrine Neoplasia
Are both mutations of the RET gene dominant or recessive?
both are dominant
What is the most common X-linked recessive disease?
Duchenne Muscular Dystrophy
What is the function of dystrophin?
to link the cytoskeleton to the extracellular matrix
What two types of proteins often feature recessive inheritance patterns?
enzymes and proteins involved in transport/storage
What is a proband?
person serving as the starting point of genetic study of a family
What are two autosomal recessive diseases?
CFTR and PKU
What is the acronym for remembering autosomal dominant diseases?
HNA - OFL
What is a key feature of autosomal dominant inheritance?
one parent is likely effected
How do CAG repeats correlate with Huntingtons Disease?
more CAG repeats = more severe of disease
What is the most common X-linked recessive disease?
DMD
Which disease almost exclusively rises from a mutation hotspot?
anchondroplasia (523)
What is the major source for maternal mutations?
non-disjunction
What is the major source of paternal mutations?
replication errors
What type of collagen is defective in osteogenesis imperfecta?
Type I
What does the dominant negative effect mean?
one mutated protein may destroy the entire complex
Defects in what protein cause Li-Fraumeni?
p53
What is a Barr Body?
inactive female X-chromosome in a somatic cell
Where do Barr bodies condense?
at the periphery of the nucleus
What is a common X-linked dominant disease?
Incontinentia Pigmenti
Incontinentia Pigmenti features what defective protein?
NFKB Essential Modulator (NEMO)
How much higher is the mutation rate in mitochondria than it is genomic DNA?
10x
What is heteroplasmy?
presence of more than one type of organeller genome within a cell
How is mitochondrial DNA passed down?
from mother to all offspring
What receptor is mutated in achondroplasia?
FGFR3
What disease features a defective ND1 gene? What protein does this defective gene affect?
ND1
Complex I
Inborn errors of metabolism are what kind of genetic disorder?
autosomal recessive
