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165 Cards in this Set

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Molecular marker
a site of heterzygosity for some type of DNA change not associated with any measurable phenotypic chance> The two basic types of molecular markers are those based on nucleotide differences and those based on differences in the amount of repetitive DNA.
The two basic types of molecular markers are
those based on nucleotide differences and those based on differences in the amount of repetitive DNA.
Types of Donor DNA:
Genomic DNA: DNA obtained directly from the chromosomes of organisms under study. It is the most straightforward source of DNA. It needs to ce cut up before cloning is possible
CDNA (complementary DNA) a double stranded version of an mRNA molecule. More useful thatn mRNA because it is more stable and for eukaryotes, contains no introns.
Chemically synthesized DNA
Genomic DNA
DNA obtained directly from the chromosomes of organisms under study. It is the most straightforward source of DNA. It needs to ce cut up before cloning is possible
CDNA
(complementary DNA) a double stranded version of an mRNA molecule. More useful thatn mRNA because it is more stable and for eukaryotes, contains no introns.
S1 nuclease
cleaves the loop that is formed when reverse transcriptase makes a loop that is completed by DNA poly 1
Restriction endonucleases
cut from within. They exist to protect a cell from foreign DNA. Unually cut at palindromic sequences
Modification methylase
methylates at restriction endonuckease sites to prevent EcoRI from cutting at the site
Chance of a restriction endo site exsisting in genome
= (1/4)^n
N= # of bases in recognition site.
Cloning vector
a small plasmid with only one restriction endoduclease site not within a gene essential for replication.
Types of cloning vectors:
PBR 322 – has ori, ampr, tetrr, restriction sites (BamHI) within tertr, Tst restriction site within AmpR
1. Transformed cells have Tet resistance
2. clone foreign DNA into plasmid disrupts the AmpR gene, cannot live of Amp therefore, the plasmid has the foreign DNA in propperly

pUC 1ori8 – Amp res, lac Z with mcs,
PBR 322
has ori, ampr, tetrr, restriction sites (BamHI) within tertr, Tst restriction site within AmpR
1. Transformed cells have Tet resistance
2. clone foreign DNA into plasmid disrupts the AmpR gene, cannot live of Amp therefore, the plasmid has the foreign DNA in propperly
pUC 18
ori, Amp res, lac Z with mcs,

Ecoli + NO plasmid = dies on amp
Ecoli + plasmid = live on Amp
Ecoli + plasmid with insert = no Beta gal, colonies are white.
How do you construct a cDNA library?
1. get cell line
2. separate RNA onto colum with oliho T’s
3. separate mRNA from other RNA
4. Use reverse transcriptanse to make 1st DNA strand
5. use Rnase H in low concentrations to knick RNA strand
6. Use DNA poly 1 to make second strand
What are cDNA libs used for
Expression studies etc
Guessomers
(degenerate probes) of single stranded DNA that can be radioactively labled, are apx 8 am acids long, and are used to screen a cDNA library.
Screening a cDNA lib
1. take plaque and replica plate
2. incubate nitrocellulose in alkali to break open phage and make the DNA single stranded. Block nitrocellulose from sticking to probe with powdered milk.
3. use a degenerate probe with a label to hybridize to the target DNA. (seal-n-aneal at 65 degrees)
4. Use autoradiography to determine where hybridized probe is
5. return to original plate
Southern Blot
used for genome ananlysis. Uses gel eletrophoresis (smaller molecules move through gel faster)
How is a southern blot used to test for different numbers of transposable elements in different strains?
First, the DNA sequence of the transposable element must be known. You must also have a labeled probe that will anneal to the trans element in question.
1. cut each strain’s DNA with restriction endo that cuts outside of the gene of interest. You will get pieces of different sizes.
2. separate by size using an electro gel
3. transfer DNA to filter by putting the gel in a salt solution bath and placing paper towels and wick action to move the DNA
4. take filter and hybridize with labeled probes
5. remove unbound probes by rinsing
6. x ray film audoradiograph
7. number of bands indicates number of copies of the transposable element
Northern Blot
Used for gene expression studies. Uses RNA as target not DNA
1. obtain RNA from different tissue samples, individuals etc…
2. separate by gel electro
3. blot
4. hybridize with cDNA as a probe for particular gene
5. rinse
6. audoradiography
7. if band is there, that means the gene is present. More than one band indicates alternative splicing
Western Blot:
target is a protein, probe is an antibody
1. boil protein to denature
2. Add SDS (a detergent) to give protein a negative charge
3. gel electro
4. blot
5. add specific antibody (primary first, then secomdary that has a color reacton when bound with the first)
6. If you find a specific protein the molecular weight should be right and only that protein will bind with the antibody.
SNP
single nucleotide polymorphism
RFLP
restriction fragment length polymorphism (an SNP in a restriction site)
Rflp analysis:
1. take d.s DNA that has different alleles. These alleles may be due to a different number of restriction sites.
2. Get a probe that overlaps segments
3. cut with rest endo
4. southern
5. probe with radioactive label
6. autoradiography
7. number of bands + 1 indicates number of restriction sites
shuttle vector:
a vector that can replicate in multiple hosts. An expression shuttle vector needs: ecoli ORI, ecoli selectable markers, mammalian ORI (usually from a virus) mammalian selectable markers, mammalian promoter. Shuttle vectors can be easily grown in ecoli but expressed in a euk cell for more accurate translation and post transl mods
position cloning
a tern that can be applied to any method for finding a specific clone that makes use of information about the genes position on its chromosome. Two elements are needed for position cloning: 1. some genetic landmarks that can set boundaries on where the gene might be. Landmarks might be RFLPs or polymorphisms. 2. The ability to investigate the continuous segment of DNA extending between the deliminated genetic landmark.
Chromosome walk
a procedure used to find and order clones falling between genetic landmarks.Can be bi-directional. The sequence of a landmark near a gene is used as a probe to identify a second set of clones that overlaps the marker clone containing the landmark but extends out from it in one of two directoions. (The end of a RFLP probe used to screen a library to get closer to gene)
For dideoxy Sanger sequencing you need
DNA polymerase , 4 dntp’s, ddATP (or another ddNTP) at low concentrations because you don’;t want termination at only one place)
For regular PCR you need
two primers (forward and reverse primer), extracted DNA, all 4 dNTPs, DNA poly (Taq polymerase) As PCR proceeds pieced of desired length increase exponentially whicle longer pieces increase only arithmically.
For Cycle sequencing you need
100bp fragment to be sequenced with part of a known sequence, primer (with no labels), all 4 dNTP’s, Taq polymerase, at low concentration ddATP with fluorescent lable (eacj ddNTP has a different color label)
1. let run
2. get set of diff fragments with diff fluorescent labels
3. separate by size by capillary
4. output: peaks of color
Restriction Map
a physical map of DNA. Must ask, is the DNA circular or linear
How to create a knock out?
In yeast: insert vector with homologous regions flanking a drug resistance gene. Cross over between the gene in the chromosome and the vecotror will insert the drug resistance gene into the gene of interest, deactivating it. This method may be problematic because ectopic insertion is common.

In mice:
Need : a region of gene homologous to target gene that is to be knocked out, neo resistange gene in the middle of the homologous genbe that is resistant to G418, herpes virus thymidine kinase (tk) that makes cells sensitive to gancylovir. The inser looks like this:
[///gene///| neo res|///gene//| tk |

1. embryonic stem cells are transformed. If, gene is insterted just at the target gene and NOT ectopicly then only the region between the homologous regions (neo res) will be insterted and the tk gene will NOT.
2. select for cells resistant to G418 = cells with some sort of insert
3. select against cells with resistance to gancyclovir = cells that die have insert at only the right place
4. cells with insert in correct place are HETEROZYGOUS for the knock out (because it is incredibally rare that insertion would take place in both copies of the gene)
5. insert stem cells into blastocytes
6. grow mice and mate to get knock out homozygotes
PNS
positive negative selection. Main ,ethod used in KO technology
mammilain blastocite
is an embryo that has:
Trophoblast- a hollow sphere of cells that will go on to implant in the unterus and develop extraembryonic membramnes (such as the placenta, umbilical cord and amnion) and the inner cell mass that will develop into the baby
Trophoblast
a hollow sphere of cells that will go on to implant in the unterus and develop extraembryonic membramnes (such as the placenta, umbilical cord and amnion) and the inner cell mass that will develop into the baby
The cells of the inner cell mass are
pluripotent, meaning that each is capable of producing descendance representing all of the hundreds of differentiated cell types.
To gow ES cells in culture:
1. remove oter trophoblast layer
2. separate inner mass cells and culture them on a plate of feeder cells
3. isolate single cells and grow them as clones
4. test the clones
The clones each had a normal human karyotype, high levels of telomerase (which indicates that they are immortal),the cells could make teratomas (which have the different cell types)

ES cells injected into an embryo with form a chimeric organism, with cell types from both the ES donor and the norm organism. By mating rhe chimerics can yield offspring with just the ES donor DNA.
The feeder laye
continues the culture without differentiating the cells. It is a monolayer of cells that has been treated so that the cells can no longer dicide. They continue to metabolize.
FISH
fluorescent in situ hybridization. Cells in which a probe will hybrizize to DNA are still intact.
Reporter genes:
This is a technique used to determine which part of the 5’ regulatory region has what function. The reporter gene is one that is easy to detect. The reporter gene will be located in a vector instead of a gene of interest
-------5’ reg--------prmtr-----[gene]

1. This is cloned many times over
2. Many copied of this are incubated with an EXO nuclease that chews in from the 5’ region to get different lengths of the 5’ reg region:
------------------------[gene]
--------------------[gene]
-------------[gene]
-------[gene]
3. a linker is attatched (so that sick end will form _, and the gene of interest is cut off.
4. the diff size 5’ reg regions are ligated into a vector with the reporter gene
5. ecoli is transformed and plasmids are cloned
6. plasmids are isolated and can be put into a diff type of cell (such as a liver cell)
7. measure amount of reporter gene produced
8. lots of reporter from a certain plasmid means that the promoter and enhancer has not been digested. Very little reporter means no enhancer. No reporter means no promoter.
In order to use somotic cell gene therapy the candidate disease must
have irreversible pathology and less that 100% of the norm protein is therapeutic.
In vivo gene therapy
Retroviral vectors without virulence gene are used. The problem is, the gene can insert anywhere, sometimes causing the loss of function of other genes
Ex viv gene therapy
genes are taken from patient, altered, grown in culture and retuned. For ADA this must be repeated because T cells die.
Euk genes must be able to
turn off expression of most genes in the genome and generate thousands of patterns of gene expression with a limited number of regulatory proteins.
Promoter
where RNA ply and helper proteins bind. Must be located at relatively exact distances from gene.
Promoter proximal elements
regions near the promoter that are cis acting that bind to proteins that in turn assist the binding od RNA poly II to the promoter. Found within 100-200bp of promotor
Enhancer
elements located at a relative distance either upstream or downstream of a promoter that increases the level of transcription. 50 kb or more. Enhancers work with specific activators that interact with the preinitiation complex
GTF
help construct the preinitiation complex
Silencers
the opposite of enhancers. Silencers act like repressors but turning genes off in euk is primarily a function of the structure of chromatin not silencers.
GC rich box
a promoter proximal element
CCAAT box
a promoter proximal element. Binds to transcription factors CTF and NF1
The transcription factors that bind to promoter proximal elements are
constitutively expressed in all cells at all times
activators
bind to enhancers. Different enhancer modules may bind different enhancers. They increase the rate at which intitation of transcription happends. Activators don’t always make contact with the preinitation site.
Chromatin
complex of DNA, RNA and protein that make up a chromosome. When chromatin is loose TF and activatiors are needed to turn of transcription
Dna Binding Protein – an architectural protein that aids in the bending of DNA
Enhancasome
large protein complex that act synergeticaly to activate transcription
CBP
coactivator that lands on (is drawn by high affinity to) activators and increases the rate of transcription
Coactivator
a special class of regulatory complex that serves as a bridge to bring together regulatory proteins and RNA polymerase
Mutation dominance is due to either
1. happloinsuficiency, 2. non functional subunits of a enzyme (like the I in the lac operon) 3. the genes under the regulatory control of the activators, porotors, or enhancers of another gene because of an abnormality in the chromosome causing abnormal expression. This could be because of translocation. An enhancer of another gene will boost transcription of the translocated gene. The gene will then be dominant.
Histone
a class of proteins that make up the nucleosome. Histones are an octomer cponsisting of two types of each protein (H2A, H2B, H3 and H4) The DNA is wrapped twice around the octamer. Histones are positively charged and are attracted to negatively charged DNA.
Heterochromatin
chromosomal regions that are transcriptionally inactive and stain more densily with Feulgen, a dye that binds to DNA.
Euchromatin
less condensed cromatin with constitiutive transcription
Constitutive heterochromatin
tight chromatin around the centromeres and telomeres.
Facultive heterochromatin
shuts of the chromosome
Why is one of the X chromosomes inactivated in humans?
One X chromosome provides enough of the gene products needed. Dosage compensation is achieved by randomly turning off one (actually 70% of the genes) of the X chromosomes during early stages of development. The inactivated cell will be passed on to all progeny. Not all cells will have the same X turned off which may result in “splotchiness”. In oogenesis both X chromosomes are again turned on.
Barr Body
the inactivated chromosome is a highly condensed heterochromatin structure. Barr bodies = num x chrms -1
Epigenetic inheritance
the progeny of a cell line will habe the same X chromosome turned off.
Imprinting
(parental imprinting) When a gene is expressed only when it comes from a certain parent. Very few genes are imprinted but a K.O. mouse for methylation dies as an embryo.
Maternal imprinting
when a gene is expressed only if it comes from the father (This is because the mother’s gene is inactivated)
How does imprinting occur?
There is no chance to the to the DNA sequence. Rather, the cytosine base of a GC dinucleotide are methylated ( - CH3) by methyltransferases. The level of methylation generally correlates to the transcription state of a gene: active genes are LESS methylated than inactive ones.
Why does imprinting occur?
One theory is the parentaly conflict hypothesis. If different fathers have embryos in the same mother the mother tries to downregulate certain genes to keep the gene pool equal from all fathers.
Methyltransferase
adds a methyl group
Maintenance methyltransferase
acts on hemi methylated DNA . Once a pattern of methylation is established it will be maintained throughout replication.
CpG island
in some genes a region near the 5’ promoter end that is methylated to inactivate the gene.
Prader-Willi
a disease of moderate retardation and obesity caused by the deletion of the parentally donated, active PWS gene and paternally imprinted (not active) AS gene. Deletion of the genes is from father.
Angelman’s
a disease of sever retardation and inappropriate laughter caused by the deletion of maternally active AS gene and the maternally imprinted PWS gene. Deletion of the genes is from mother.
Rpd3
an enzyme that is part of a complex that deacydylates N tern tails of histones
RD
repressor domain. Binds the deacetylation compex to the DNA binding domain
Gcn5 complex
acetylates histones. Binds to enhancesome complex, acetylates histones, recruits CBP and SWI-SNF. Loosens chromatin
Methyl CpG binding proteins
may recruit histone deacetylation
SWI –SNF
nudges aside histones
HAT
histone acetyltransferase
HDAC
histone deacetyltransferase
Silent chromatin
NOT heterochromatin. A euchromatin region that can assume a more condensed chromatin structure.
How was it proven that histone H4 plays a role in inducible gene regulation?
Put in H4 gene under control of an inducible promoter to see how mutant kos for certain genes will respond. When H4 transcription was insuced to be high, there was normal regulation of both constitutive and inducible genes. When H4 transcription was induced to be low there was normal regulation for constitutive genes but inducible genes were always on.
RNAi
RNA interference. The rna of one gene posttranscriptionally regulates another protein. The RNA forms a hairpin loob structure and is double stranded
Dicer
an RNase III enzyme that is responsible for processin lond dsRNA’s into siRNA’s. It none specifiacally chops up dbl stranded RNA into pieces that are 22-23 nt long
SiRNA
short interfering RNA
RISK
RNA induced silencing comples that uses double stranded RNA, picks one strand that is complementary to mRNA for a second gene and degrades that messenger
Histone tails
N terminus that sticks out of chromatin
What are the two approaches to the Genome project?
1. whole genome random shotgun cloning and sequencing (Venter/Solera Method)
a. break down genome into random fragments
b. have at least 7x redundancy
c. computer looks for overlaps
2. Ordered clone/contig/hierarchal shotgun approach
a. BAC lib (100-500kb insert)
b. Organize into contigs
STS
sequence tag sites. Pieces that will be amplified with PCR and arranged into a contig
Contig
continuous DNA
Scaffold
the ordered contigs that start to map a chromosome
How do you close gaps in a scaffold?
If the sequence is not too big, make PCR primers with the end of the known contigs and try to span the gap or,
Try to screen a YAC library with ends of contigs
Minimum tiling path
the minimum number of cloned segments you must sequence
What are the limitations to genomic sequencing?
Repetitive DNA. So DNA around the contromeres has not been sequenced.
Annotation in prokaryotes
to identify genes look for promoter, shine-delgarno seq, start condon etc.
Annotation in euk:
to identify genes look for promoter, cpG fragments, Kozak seq, exon intron boundaries, start and tem codon, poly a signal etc…
How do you find out what a gene does?
BLAST it. Compares your sequence with known sequences
Satellite DNA
highly repetitive, noncoding, non transcribed DNA. It found around chromatin and (is usually poly AT??)
Repeat tandem sequence
not sat DNA. Either a mini or micro satellite. Found throughouth the chromosome and doesn’t come out in separate peaks.
SSLP
simple sequence length polymorphisms. Either mini sats (variable number tandem repeat) or micro sats (short tandem repeats)
Mini sats
variable num tandem repeats
units of ~15-100bp with tandem repeats of 1 kb – 5kb scattered around the genokme. They are highly polymorphic in size.originally used as a DNA fingerprint:
1. cut human DNA with endo that cuts outside of the repeat
2. gel à sep by size
3. southern blot
4. prove with labeled VNTR (mini sat) dna
5. audoradiography
Thi sis not good for court because the bands can be faint if the repeat is in few copies (there is little binding to probe) or if the repeat might vary in sequence slightly
Micro sats
STRs) units of 2-4 bp repeated 10-20x very polymorphic because in replication loofs may easily form and vary the length of the repeats. A child has 1/10 to 1/20 diff loci from partent
1. use PCR primers that recognize units outside of the STRs
2. run on gel to measure size of products
13 CODIS loci
combined DNA index system. Each loci is defined by unique PCR primers for STR length. No one matched anyone else in all 13 loci except identical twins.
FISH
fluorescent in situ hybridization:
Chromosome is treated with alkali to make it single stranded
A probe is labled with a fluorescent tag
It hybridizes to the chromosome
Used esp in mitotic metaphase because there are 4 copies of each gene
Can be used to determine the number of copies of a certain chromosome
How can FISH be used to order BACs in a chromosome?
Each BACs probe gets a different fluorescence
Its place on the chromosome determines order of bacs
Psi- pseudogene
A gene that resembles another gene but is not functional. Arose from duplication issues in evolution. A gene can change in evolution to keep its function, have a new function, one copy can loose function to form a pseudogene.
Processed pseudo gen
– has no function but has no promoter, no introns, but does have a ploy A tail and probably arose form the action of reverse transcriptase.
CNV
copy number variation a source of genetic vartiation in which there is more that the regular copy number of a gene. Appx 12% of the human genome is affected.
Microarrays
way to study gene expression of all the genes in a tissue or genome to see which genes are up or down regulated under different conditions.
Transposable element
Bacterial. a segment of DNA that can move either from chromosomes to plasmid or phage. It can move around the chromosome.
IS
insertion sequences elements. Bacterial. Segments of bacterial DNA that can move from one position on the chromosome to another position wither on the same chromosome or another chromosome. The IS gene has inverted repeats at each end and a transposon gene in the middle that codes for transposase. Where the IS jumps into a genome, it causes the repeat of the target on either side of the element
Transposease
the gene that codes for a protein that can put itself into another part of the genome. Cus element out of original location, cuts at target, element is inserted and gaps are filled in
Tn5 (composite transposition)
a class of transposon in which two separate IS elements are flanking a gene and can move it elsewhere
Tn3 (simple transpostition)
A class of transposon in which the inverted repeats of an IS element flank the transposase gene as well as another gene. This is a replcated transposition.
IR
inverted repeats that flank a transposon
Long terminal Repeats (LTR)
sequences of a hundred base pairs long that flank a retro virus or a Ty element in eukaryotes.
Retrovirus
a single stranded RNA virus that employs a double stranded DNA intermediate made by reverse transcriptase for replication.
Gag
retrovirus protein that has a role in maturation of the RNA genome
Pol
retrovirus protein that encodes reverse transcriptase
Env
retroviral protein that codes for the surrounding structural proteins.
Ty element
a eukaryotic transposable element similar to a retrovirus with Gag and Pol genes but no env genes. Ty elements move around the genome because when transcribed into RNA, reverse transcriptase makes it into double stranded DNA and is inserted back into the genome.
Class 1 transposable elements
transposable elements that utilize reverse transcriptase to transpose throught an RNA intermediate. A retrotransposon.
LTR–retrotransposons
retrostransposons with Long terminal repeats like the TY element.
Copia elements
retrotransposons in drysophela
Class 2 transposable elements
DNA transposons the work like bacterial transposons
C value paradox
random differences in size between different orgainsims’ genomes.
LINEs
long interdispersed nuclear elements found in the human genome that move by retrotranspostition with the help of a reverse transcriptase but do not have LTR. 5 kb
Autonomous
self transposable. Codes for its own reverse transcriptase.
SINEs
short interdispersed nuclear elements founf in the human genome that do not code for their own reverse transcriptase.
Alu
the most abundant SINE in the human genome. It codes for the Alu restriction RNA enzyme. 200 bases long. Similar to 7SL RNA involved in protein secretion.
If there is a non disjunction the the 1st division of meiosis what will happen?
Out of the 4 possible gametes, two will be 2n with one chromosome coming from the mother and one from the father. The other 2 gametes will have no copies of the chromosome:
If a nondisjuction happends at the second meiotic division what happends?
Out of the 4 possible gametes one will have two copies of the same chromosome, one will have no copies, and two will be normal:
How to make a human karyotype;
1. cell culture of white blood cells with mitogen to stimulate the white blood cells to reproduce
2. Incubate with colemide to arrest mitosis at metaphase so that chromosomes are easy to see.
3. ceterfuge to spin down cells
4. remove solution medium and add hypotonic solution (distilled water) to cells so that they swell and the chromosomes can be removed
5. the chromosomes are spead out on a slide
6. the slide is stained with Giemsa to give a pattern of light and dark bands
7. chromosomes are photographed, cut out, and arranged into a karyotype
karyotype
map of human chromosomes
mitogen
stimulates reproduction of cells
colemide
a plant compound that disintegrates the spindle apparatus and stops cell divition at metaphase where chromosomes are thickest and easy to see.
Giemsa
stain for chromosomes
Chromsomes landmarks
Telomeres
Satellites – found in the p arm of chromosome 13, 14, 15, 21, 22
Centromere – long tandem repeat of alpha satellite, a 171 bp sequence, 98 – 99% similarity of sequence at centromere decreasing with distance from centromere.
G banding
a type of chromosome stain. Metaphase chromosomes are spread with low concentration of protease, then staines with Giemsa. The advantage to this staining method is that each chromosome can be identified.
Stalks
regions of a chromosome that don’t stain well. They code for ribosomal RNA. They come together in interphase to form the nucleolus.
P arm
short arm of the chromosome
Q arm
long arm of the chromosome
Chromosome painting
a preparation for chromosomes in which specific probes are made for each chromosome. The probes are labled with different color flouraphores. They are treated with alkali and the probes hybridize. The chromosomes are scanned by a laser and a computer assigns different colors to the different chromosomes.
How can chromosomes be abnormal?
Either in number or size
Euploid
any multiple of the haploid n number. Normal. A viable human euploid is 2n = 46
Aneuploid
not euploid due to a nondisjunction. This is an aberration in number of chromosomes
Down syndrome:
Aneuploidy 47, +21 (there is an extra 21 chromosome)
Autosomal aneuploidy
all are lethal early in development because every chromosome has haploinsufficiency. Only trisomy of chromosome 21 is viable (Down syndrome) probably because chromosome 21 has the smales number of genes of any autosomal chromosome.
Sex chromosome aneupleudy
XXX – females, 1/1000, no excess fetal mortality but some developmental delays. There is no abnormality probably due to X inactivation
Klinefelters – XXY aneuploidy 1/1000 male births. Causes no excess fetal mortality. The man is small and sterile with mild retardation
XYY – 1/1000 male births. No excess mortality. Male is tall with a depressed IQ of 10 points ans some behavioral differences such as in increase in criminal behavior (not violence)
Turner’s – XO very high fetal mortality. Short, sterile, poor at 3d problems not retarded. Often this occurs in a mosaic pattern. Due to the fact that the 15% of genes that are not inactivated on the X chromosome
XXX
females, 1/1000, no excess fetal mortality but some developmental delays. There is no abnormality probably due to X inactivation
Klinefelters
XXY aneuploidy 1/1000 male births. Causes no excess fetal mortality. The man is small and sterile with mild retardation
XYY
1/1000 male births. No excess mortality. Male is tall with a depressed IQ of 10 points ans some behavioral differences such as in increase in criminal behavior (not violence)
Turner’s
XO very high fetal mortality. Short, sterile, poor at 3d problems not retarded. Often this occurs in a mosaic pattern. Due to the fact that the 15% of genes that are not inactivated on the X chromosome must be necessary for normal female development. There are no internal sex organs.
Abberations in chromosome structure are due
Deletions- either caused by two breaks in normal chromosome that are rejoined without the middle segment of by a loop caused by repetitive elements facing the same direction. Can also cause duplication caused by a cross over event between homologous chomosomes
Inversions – caused be two breaks in a chromosome in which repairs caus einversion of by a loop caused by inverted repeats facing each other.
Translocation
Balenced
Robertsonian
They can arise from breakage and rejoining or from recombination between repetitive sequences.
Balenced reciprocal translocatio
translocation between non homologous chromosomes that maintaines all the genes (nothing is lost) and evenly switches parts of 2 chromosomes. It can cause reduced ferticilty because only 2/4 gametes will be balanced.
Robertsonian translocation
A translocation in which chromosome 21 and 14 join long arms. Can cause down if, someone who has one norm 14, one norm 21 and one 21+14 mates with a normal person. The short ae of chromsm 21 is just chromatin.
Amniocentisis
15 – 16th week. Provides cells for chromosome analysis and gene testing. But this takes a long time
Chorionic villus sampling
10 – 12 week
Nuchal translucency
the neck and fold of skin od a down baby is filled with fluid and more transleuscent in ultrasound. Must be confirmed with genetic testing.
How do you get human ES cells to form neurons?
Human embryonic stem cells were co cultured with immortalized human fetal midbrain astrocytes. This mimics the invivo conditions that cause stem cells to differentiate into neurons
What is an embryoid body and why is it used?
It is an aggregation of stem cells. It is used to obtain neuronal precursors
what is hTERT and why does it immortalize astrocytes?
HTERT is the catalytic subunit of telomerase. It immortalizes astrocytes by maintaining chromosome length.
what danger of ES therapy was shown by this work?
The inner cells of the graft keep dividing and do not differentiate. They may be tumerogenic