Exam 2 concepts Flashcards
what are some of the factors that can influence birth defects in childhood?
- multifactorial
- unknown
- teratogens
- monogenic
- chromosomal
what are the classification classes of birth defects
- malformation
- disruption
- deformation
- dysplasia
- sequence
- syndrome
- association
what are some traits associated with cardiac defects
- major cause of death in first year of life
- common anomaly is ventricular septal defects
- incidence is 5-8 per 1000 births
what are some of the developmental milestones as it pertains to neural tubes?
18th day-neural plate developmental
24th day-cranial closure
26th day-caudal closure
what are the different spina bifida degrees?
- spina bifida occulta
- lipomeningocele
- meningocele
- myelomeningocele
in the last decade, what has folic acid/vitamin b0 been used for?
for prevention of neural tube defects (NTD), coronary artery disease (CAD), stroke and colorectal and cervical cancer
polymorphisms in folate metabolism enzyme encoding genes can result in what?
risk factors for neural tube defects. the enzymes are responsible for recycling of folate
what are the fetus malformations that are results of using thalidomide?
amelia, phocomelia, hypoplasia and absence of some bones
what are the immunomodulatory properties of thalidomide therapeutic properties?
Inhibition and stimulation of cytokines Co-stimulation of primary human T cells Modification of surface cell adhesion molecules Induction of NK cells Treats leprosy
what are the non immunomodulatory properties of thalidomide therapeutic properties?
Anti-angiogenic activity
Anti-proliferative and pro-apoptotic activity
Treats cancer
what is the potter sequence?
urethral agenesis–> oligohydramnio–> fetal compression in utero, growth deficiency, multiple malformations, altered facies, limb positioning defects
what are some other health problems that down syndrome could increase the chance of?
- heart defects
- thyroid disease
- nearsightedness
- farsightedness
- alzheimers
- leukemia
what are some of the personality problems with Fetal alcohol syndrome
Difficulty with time
Being where they should be on time
Problems managing money
Difficulty transferring learning to other situations
Difficulty determining what to do in a given situation
what does VATER stand for?
V - Vertebrae problems,
For example, abnormally formed vertebrae, and extra ribs.
A - Anal Anomalies and sometimes rectum problems.
For example, there is no opening where the anus should be
T - Trachea problems.
For example, there is a connection between the trachea and esophagus.
E - Esophagus problems.
For example, part of the esophagus is missing.
R - Radius (lower arm bone) problems
For example, the larger lower arm bone is abnormally formed
what factors influence teratogenicity?
Dose Route Frequency of exposure Duration of exposure Concurrent exposures Concurrent illness Genetic susceptibility
what are the teratogenesis mechanisms
- Mutation
- Chromosomal aberrations
- Mitotic interference
- Nucleic acid metabolism alteration
- Energy metabolism interference
- substrate deficiency
- pathway inhibition - Cell membrane alterations
what are the developmental gene families?
homeobox (hox) gene family Paired box (pax) gene family
what are the developmental gene pathways?
Fibroblast growth factor and receptors
Sonic hedgehog pathway
Neural crest cell migration network
what are the explanations for an important gene family produces only 3 rare human syndromes?
One HOX gene may be able to compensate for deficiency in another (redundancy)
HOX genes are so important that when mutated inevitably produces early pregnancy loss (no viable babies born)
what is the treatment for aniridia?
colored eye lenses in order to reduce the light inlet
what are the cell signals used to organize itself into embryonic tissues
juxtracine signal and paracrine factors
what are the examples of signals used for sonic hedgehog pathway?
to differentiate, die, and migrate
what are the two ways shh does its signals?
-signals to adjacent cells when tethered to the plasma membrane -signals in long range as freely diffusible molecule
what are the symptom ranges of holoprosencephaly?
mild (anosmia, or a single central incisor) to moderate (cleft lip or palate) to severe (cyclopia)
HH signaling is linked to an increasing number of what?
cancers, can be cancers with mutations in the HH pathway or cancers with autocrine requirements for HH ligand
what are the 4 types of waardenburg syndrome?
type 1: hearing loss and white forelock
type 2: very similar to type 1
type 3: severe form with limb abnormalities
type 4: waardenburg and hirschprung
why does loss of melanocytes lead to deafness?
melanocytes produce endolymph in the stria vascularis. stria vascularis uses that endolymph for the scala media where the organ of corti is. Organ of corti contain auditory sensory cells
what are the mutations associated with male pseudohermaphroditism?
SF1 mutation, SOX9 mutation, and WT1 mutation
Any factor
raising testosteron level
will serve as SRY surrogate
and will lead to what?
masculinization
of female genitalia
(Female pseudohermaphroditism)
what are the factors raising testosterone levels in females?
A) Maternal androgen ingestion (exogenous)
B) 21-hydroxylase deficiency
enzyme deficiency
what phase does the genome work to express genes
g1 and g2
what is the ploidy for sperm and eggs vs somatic cells
sperm and eggs are haploid and somatic cells are diploid
what can be the result of changes in the chromosome number and structure
birth defects, mental retardation, infertility, miscarriage cancer
what does chromosome morphology depend on
the position of the centromere
what are the methods of chromosome analysis
- chromosomal banding
- FISH (fluorescent in situ hybridization)
- CHG (comparative genome hybridization)
how does FISH work
fluorescent labeled DNA probe anneals to DNA within the metaphase chromosomes by its complimentarity . Then can confirm if a baby has a certain disease
what is SKY useful in?
in identifying complex karyotypes especially in cancer
individual chromosomes territories are what
tissue specific
the relative positions of chromosomes in an interphase nucleus depend on what
the proportion of genes and the A+T content
how does CGH work?
- mix patients dna with normal dna
- put the mixed solution on a metaphase spread and and with the rest of solution array pieces of genomic dna
- for the spread and array red sections mean gain so duplication. Green means loss which is deletion
subtelomeric chromosome rearrangements are common in whom
kids with idiopathic mental retardation
when does crossing over occur
during prophase I of meiosis (pachytene)
in a process called synapsis
within synaptonemal complexes
what is dicytyotene
when Ova arrested for 10-50 years
in Meiotic prophase I (at birth)
what does long waiting in dictyotene do
leads to increased probability of non disjunction of chromosomes
The relative frequency
of new autosomal dominant mutations
in children increases logarithmically
with what?
paternal age
what is 2 paternal and 1 maternal called
triploid, large placenta, very small fetus
what is the result of 2 maternal and 1 paternal
triploid, some live through 2nd trimester, very rarely to term intrauterine growth retardation
what does monosomy lead to
miscarriages
what does trisomy lead to
patau syndrome (+13) edwards syndrome (+18) down syndrome (+21) and miscarriages
what are structural abnormalities of chromosomes caused by
translocations
deletions and insertions
inversions
what does the clinical outcome of structural abnormalities depend on
the net gain of loss of chromosome material
what is the net effect of robertsonian translocations
no changes
in gene expression on q-arms;
Loss of rRNA expression,
Cell will not feel the loss phenotypically
due to rRNA gene redundancy
what are some other traits of robertsonian translocation
- example of balanced abnormality
- abnormal karyotype
- hybrid mini chromosome
balanced abnormalities may lead to what
unbalanced abnormality in the offspring
As with all chromosome abnormalities, chromosomal inversions and rings problems depends on what
what is found, size of the ring, how much material was lost, which chromosomes are involved
what kinds of chromosomes are always lost in mitosis
acentric and dicentric
what are the two kinds of chromosomal abnormalities
- balanced, no net gain or loss of chromosomal material. Translocation and inversions.
- unbalanced, net gains and loss. deletions and insertions
phenotypes are not produced in balanced chromosomal abnormalities except in what cases?
- chromosomal break disrupts important gene
- break separate gene from regulatory element
robertsonian translocations are always what
unbalanced, as small acrocentric fragment is lost
what happens if a chromosomal translocation happens in a somatic cell?
cancer
what enlarges a telomere
telomerase, a reverse transcriptase, extends the lagging dna strand
what are the reasons for tumor development being a complex process?
A multitude of events (greater than 4)
Each event has low probability, requires years for full phenotype to develop
Mut events happen in succession of each other
Because of that
cancer is typically a disease of old age
what are the steps to genome change
- point mutations
- chromosomal rearrangements
- changes in methylation pattern
- regulatory changes in gene expression
what are the gene involved in tumor development
- tumor suppressors
- oncogenes
- lots of genes that have marginal influence on tumor growth
- lots of genes that change their status as consequence of malignization
are oncogenes or tumor supressors dominantly inherited?
oncogenes are dominantly inherited (one defective allele can predispose the cell to tumor formation) and tumor suppressors are recessive(Mutation in one allele predispose human to cancer, but do not cause it)
how do tumor suppressor genes act in recessive fashion?
If one copy is gone/mutated, second normal allele will function.
If both copies are gone/mutated, cancer can progress (two hit hypothesis).
Replace a single normal copy and cells return to normal (cell fusion assay).
what are the ways oncogenes influence status changing?
- activating point mutations
- translocating under strong promoter
- amplificiation
- overexpression
what are the ways tumor suppressors influence status changing
- inactivating point mutations
- promoter methylation
- gross chromosomal deletion
- under expression
what are the two alternative statements describing tumors?
- tumors are clonal
- tumor is a mix of different cell populations (tumors are heterogenous)
what are some traits towards the claim that darwinian selection is in tumors
-tumor can quickly react to changes in environment (like to treatment of patient with drug or radiation)
-Tumor reacts via expanding of pre-existing population of resistant cells
or by rapid divisions with producing of multiple clones. 99% of them non viable,
but 1% is enough to win a game
what are the two main ideas about metastasis?
- needs many steps and any step is rate limiting
2. cancer cells should profoundly changes their behavior to get an ability to spread through the organism
what is the sequence of metastatic events
Genesis of new vasculature (angiogenesis) Detachment of tumor cell from other cells Invasation (entry to vessel) Evasion of natural host defences Arrest in small vessels Attachment to vessel walls Extravasation Establishment of a new growing colony
what is step 1 of metastasis?
Neovascularisation (neoangiogenesis), Every microtumors
>1-2 mm in size need to
grow new vessels
to escape from hypoxia
what does the tumor secrete during step 1 of neovascularization
pro-angiogenic factors as VEGF, FGFs, IL-8, prostaglandins
what is step 2 of metastasis
detachment of tumor cells from neighboring cells. Also playing role
in the primary tumor invasiveness.
what is step 3 of metastasis
entry of tumor cells to vessel,
what is step 4 of metastasis
evasion of natural host defenses, Because cancer cells are altered-self cells, one would expect cancerous cells to elicit a cell-mediated response
what are steps 4-7 of metastasis
Arrest in small vesselsand attachment to vessel walls. Extravasation.Establishment of a new growing colony
