Robbins chapt 5 Flashcards
Which is the type of genetic disease that is:
- caused by interaction between variants of fenes and environmental factors
- no single susceptibility gene is necessary OR sufficient to produce the disease
- common
complex multigenic disorders
Can mutation in somatic cell cause hereditary disease?
no
what is the difference between conservative and non conservative missense mutation? And a nonsense mutation?
conservative: causes llittel change in the function of the protein bc substituted amino acid is biochemicallyu similar to the original
nonsense mutation: change a codon to a stop codon (chain terminator)
mutations of non coding sequences can lead to____
reduction or total lack of transcription of DNA
This type of mutation affecting a number of base that is not a multiple of 3 causes an alteration of the reading frame of the DNA strand, usually leading to the incorporation of a variable number of incorrect amino acids followed by truncation resulting from a premature stop codon
frameshift mutation
name 2 characteristics of trinucleotide-repeat mutation
- usually affects guanine and cytosine
- dynamic, meaning the degree of amplification increases during gametogenesis, influencing therefore the pattern of inheritance and the phenotype of the disease
Which disorder type is virtually always the result of mutations in single genes that have large effects?
Mendelian disorders
What is pleiotropism and genetic heterogeneity?
pleiotropisme: a single mutant gene may lead to many end effects
genetic heterogeneitu: mutation of several genetic loci may produce the same trait
what does a 50% penetrance mean?
50% of those who carry the gene express the trait
The transmission of diorders produced by gain of function mutations is almost always autosomal ___________ (dominant or recessive)
dominant
These are usual characteristics of dominant/recessive traits?
- expression of the defect more uniform
- complete penetrance common
onset frequent in early life
new mutations rarely detected clinically - many of the mutated genes encode enzymes
All sex-linked disorders are _______ X/Y linked and almost all are ____ recessive/dominant
X (because all of the genes located in Y are involved in spermatogenesis
recessive
Why is it remotely possible for women to have expression of heterozygous X linked condition in female?
because of the random inactivation of one of the X chromosome in each cell. Proportion of cells in which the mutant X is acive is variable, and can sometimes be inactivated in most cells
It is also possible that women express the disorder partially
Osteogenesis imperfecta, epidermolysis bullosa are two conditions resulting deom mutation affecting _______ ( which component of tissues?)
collagen. Ehlers Danlos syndrome also
When lysosomal enzymes are produced, how do they manage to be only going in the lysosomes?
Because of post translational modifications in the Golgi complex including attachment of terminal mannose 6 phosphate groups. This is recognized by receptors found on the inner surface of Golgi membrane, and lyzozyme bind to them.
Why are mitochondria affected by lyzosomal storage diseases?
Autophagy is important for the turnover of mitochondria (mitophagy), (accumulation of undigested macromolecules in lyzosome = rate of production of autophagic vacuoles reduced) Damaged mitochondria generate free
radicals and release molecules that trigger the intrinsic
pathway of apoptosis.
3 roles of lysozmes?
- membrane repair
- immunity
- autophagy
organ affected in lysozomal disease is determined by 2 factors:
- tissue where most of the material is found
- location where most of the degradation normally occurs
Spleen and liver are often enlarged with lysosomal storage disease because?
Because cells of the mononuclear phagocyte system are especially rich in lysosomes and are involved in the degradatuib of a variety of substrate
Marfan syndrome: Which component of the cell is affected? What type of mutation?
Missense, fibrillin-1
Fibrillin is particularly abundant in (name 3 structures in the body):
aorta, ligaments, ciliary zonules that support the lens. Also cause bone overgrowth and myxoid changes in mitral valves
Classic Ehlers danlos syndrome: which type of collagen is affected (1 to 5), avec clinically what does it causes?
type V, skin and joint hypermobility, atrophic scars, easily bruising
Ehler danlos syndrome: arthrochalasia type is when which type of collagen is avected? (I to V)
I
metabolism of lipids Where is ApoC lost (ApoB and ApoE retained) and VLDL is converted to IDL (or VLDL remnant)?
in the capillary of adipose tissue and muscle
Which protein is left on the IDL that have not been taken by the liver?
ApoB. The IDL not taken by the liver is subjected to metabolic process that removes most of the remaining triglyceride and ApoE
how are named the specialized region of the plasma membrane that have clusters of LDL receptors?
coated pits
complex multigenic disorders VS chromosomal disorders or disorders relted to mutations in single genes with large effects,
Which has the most penetrance and is more common?
complex multigenic disorders
what is a point mutation with coding sequence?
substitution of a single base
What is a conservative missense mutation?
point mutation that give a similar amino acidhat
what is a nonsense mutation?
single base mutation that gives a stop codon
which are the most important non coding RNA?
microRNA and long non coding RNA
autosomal recessive: enzymes are affected often, vs in autosomal dominant: structural (ex: collagen) or ___________
diseases involved in regulation of complex metabolic pathways that are subject to feedback inhibition
Why no sex linked disorder that are x linked?
male with Y linked disorder are infertile
how does cholesterol supress cholesterol synthesis (which enzyme?)
inhibiting activity of HMG CoA reductase
Cholesterol also supresses the synthesis of LDL receptors, activate esterification and storage of cholesterol and uregulae PCSK9 which reduces recycling of LDL receptors
where are the lysosomal enzymees produced in the cell?
endoplasmic reticulum. Then moved to golgi apparatus
mucopolysaccharidose: in which cells are the accumulated mucopolysaccharides?
mononuclear phagocytic cells (histiocyes I guess), fibroblasts, intimal smooth muscle cells, endothelial cells
enzyme glucose 6 phosphatase: which subgroup of glycogen storage disease?
hepatic
three types of glycogen storage disease: hepatic, myopathic and a third category, associated with 2 enzymes, which are:
acid alpha glucosidase (acid maltase, causes cardiomegaly), and branching enzymes
2 main causes of aneuploidy
anaphase lag (chromosome or chromtid is left behind (out of the nucleus)) and non disjunction
which is more common: terminal deletion of chromosome or interstitial deletion of chromosome?
interstiital.
Very rare is ring deletion
what is the role of the gene XIST?
inactivation of one of the X chromosome
what is a pseudohermaphrodite?
testicule +female genitalia or ovaries + male genitalia
what is genomic imprinting?
selective inactivation of maternal OR paternal allele in gametogenesis
what is gonadal mosaicism
in some autosomal dominant disorders ex: osstegenesis imperfecta, phenotically normal parents have more than one affected child because of a mutation that occurs post zygote affecting cells destined to form gonads in the parents
2 utilities of real time PCR
infectious load, monitor the frequency of cancer cells bearing characterisic genetic lesions in blood or tissues
Amplicon lenght analysis: what is it used for?
detecting mutation that affect the lenght of DNA (deletions or expansions)
what is he advantage of next generation sequencing compared to sanger sequencing?
more sensitive, ex for cancer, because the sampling is often contaminated with stromal cells.
Primers for many genomic regions are used at the SAME time
