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38 Cards in this Set
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- 3rd side (hint)
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What are the structural chromosome abnormalities?
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Structural Chromosome Abnormalities
1. Translocation 2. Deletions 3. Isochromosomes 4. Inversions A. pericentric B. paracentric |
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Tell me more about translocations!
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1. Robertsonian
2. Reciprocal For now, just give me some deets on Robertsonian! |
ROBERTSONIAN
-Highly specialized -Has to involve two of the acrocentric (13, 14, 15, 21, 22) chromosomes -The breaks have to be around the centromeric areas of both of those chromosomes -Basically it’s a whole long arm fusion of two acrocentric chromosomes -The most common of these is a translocation between chromosome 13 and 14 --- t(13;14) -The diploid number in humans is 46 -Interestingly, if you are a balanced (phenotypically normal) translocation carrier of a Robertsonian translocation, your total chromosome number is 45 -If you are unbalanced, your chromosome number is 46 |
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If you are a phenotypically normal translocation carrier of a Robertsonian translocation, how many chromosomes do you have? What if you are unbalanced?
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-The diploid number in humans is 46
-Interestingly, if you are a balanced (phenotypically normal) translocation carrier of a Robertsonian translocation, your total chromosome number is 45 -If you are unbalanced, your chromosome number is 46 |
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How does a Robertsonian translocation form?
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-It’s a translocation between two acrocentrics (note the pink one flipped upside down)
-The break is typically in the short arm in all of those repeats where they’re similar to each other -Imagine a break in 13p and a break in 14 p -The long arms fuse together and the pieces from the p arm that have no centromeres get lost – this has no effect on phenotype because there are so many other copies of these genes on the other acrocentrics -Now what you actually have is a dicentric chromosome but those centromeres are so close to each other that they act like a monocentric. They do fine in mitosis. |
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This is a 13;14 translocation
Is it balanced or unbalanced? |
-This is UNBALANCED
-There are two chromosomes in each “slot” in the karyotype -This chromosome from here up is 13, if you were to mentally flip it and line it up, it’s a 13 -This person has 3 copies of 13q, 2 copies of 14q, forget about the p arms (we don’t care) -This person is phenotypically indistinguishable from someone with trisomy 13 where you have 3 separate 13’s I-f you saw a baby in the nursery that has trisomy 13, you really need to do a karyotype because this karyotype could have been inherited from a parent who is normal, but you’re not going to have a parent who has 3 13’s |
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This is a 14;21 translocation.
Is it balanced or unbalanced? |
-This is what a BALANCED tranlocation carrier for a 14;21 Robertsonian translocation karyotype looks like
-You have two of everything except when you get to chromosome 21 there is only 1 free standing 21 and the 2nd 21 is right on top of 14. If you were to flip it and put it down by the 21, it’s a 21 -This person has all the right number of important genes – 2 copies of all the 21q genes, 2 copies of all the 14 q genes, and 2 copies of everything else -These individuals are phenotypically normal -They are balanced Robertsonian translocation carriers Why do we worry about people who have balanced translocations? |
We worry about people who have balanced translocations and what kind of gametes form and what their chance is of having a baby with an abnormal karyotype
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What kind of gametes form if mom, for instance, has a balanced Robertsonian translocation? What is the outcome for the child in each case?
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• Let’s assume we’re talking about chromosome 14 and chromosome 21
• Let’s say the light blue is 14 and the dark blue is 21 • This is a mom who is a balanced translocation carrier with a 14;21 translocation • Here’s dad with normal 14’s and 21’s • Mom can make 6 different gametes |
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What is a reciprocal translocation?
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-Reciprocal translocations involve breaks anywhere in any types of chromosomes
-The balanced chromosome number is 46 -The unbalanced chromosome number is also 46 as well, or rarely 47 For example! -->Here we have two different chromosomes, let’s call them 4 and 6, that break -->Both of them break in the q arms, but can be p and p or p and q or whatever -->They exchange pieces of q arms so now we have two chromosomes that have translocations -->This is a derivative 2 with a little 6 and a derivative 6 with a little two -->That person should be fine – they have all the right amount of genes that are repackaged a little bit differently |
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-Patient who had a couple of spontaneous abortions – didn’t know why
-Had 3rd miscarriage and came in for chromosomal analysis -They karyotyped her, and this is what they saw. What's going on???? |
-Turned out she had one normal 7 and one short 7.
-When they looked at 21’s, she had one normal 21 and one very long 21 -From here down, this is 7q -On here, they had to take leap of faith that this was 21 q **Chromosomes don’t rearrange unless they’re BROKEN -->A 7q would not attach onto an intact 21q -->There have to be two sticky ends – need a break in 21 and a break in 7 so that a little piece of 21 goes to 7 and a big chunk of 7 goes to 21 ******Mom had rearrangement of chromosomal material such that she was a balanced reciprocal translocation carrier****** |
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When they karyotyped the fetus that she just miscarried, this is what the fetal chromosomes looked like.
What's up with this? |
-The fetus had inherited from the dad a normal 7 and 21
-From the mom, however, the fetus had a normal 7 AND the mom’s abnormal 21 (21;7) -This fetus has partial trisomy for 7q and a partial monosomy for 21q -This is an unbalanced translocation Is it surprising that this resulted in miscarriage? |
-This fetus has so much trisomy that it’s not unexpected that this would result in a miscarriage
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Then they got a karyotype of this woman. Let's take a looksee on the other side.
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-This is the lady who came to them at Gtown
-The last unbalanced karyotype was her second miscarriage -As they followed her through her other pregnancies, it shows what the possibilities are of a balanced translocation carrier -Her next child was a viable pregnancy – a little girl with totally normal chromosomes -->She inherited her normal 7 and her normal 21 -THEN she had a twin pregnancy – two boys -->The one boy got her normal 7 and normal 21 -->The other boy got both her abnormal 7 AND her abnormal 21, so he was a balanced carrier |
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What are 4 possible gametes that the translocation carrier can produce?
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(Say this is chromosome 7 in blue and chromosome 21 in black)
4 possible gametes that the translocation carrier can produce: 1. The mom can pass on her normal 7 and 21 and have a karyotypically and phenotypically normal child 2. The mom can pass on both translocation chromosomes. This is balanced. She can have a karyotypically balanced child who is phenotypically normal, just like herself The other two possiblities are where problems can occur: 3&4. If one normal and one translocation chromosome is passed on -->This leads to partial trisomy of one chromosome and partial monosomy of the other (and visa versa) |
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What happens if you have a Balanced Reciprocal Translocation showing up in prenatal diagnosis:
a. if you know mom or dad has the translocation b. if the translocation is de novo |
a. If it’s inherited from a family member who is normal and you see it in a prenatal diagnosis, and you know mom or dad has it, then you can expect it will result in a normal child, or at least no increased risk over the normal background
b. If it is a new mutation, a de novo translocation, and mom and dad both have normal chromosomes and you have a fetus that has a translocation, then there is some concern because: ??? What is the difference between these two situations? |
A. chromosome analysis is pretty crude. We can’t see what’s really going on. You have to wonder if you’re seeing any small deletions or duplications
B. even if everything is there, if the chromosome breaks in the middle of a gene, it’s going to disrupt gene function. Thus, you could change gene expression based on where the break is. -The difference is if the parent is a carrier you’ve already done that experiment – if it did break a gene it wasn’t an important gene or it broke in between genes. -In a new mutation in a fetus if you had a de novo mutation, you don’t know where that break is, so they give a 10% risk of phenotypic abnormalities in a fetus with a de novo balanced translocation -We call it balanced, but part of that caveat is that we can’t see at a fine enough level to know that it is truly balanced |
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What are the Reproductive Consequences of Unbalanced Translocations?
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**The larger the imbalance the more likely the fetus is not going to make it to term and the more likely it will result in a miscarriage
** -Conceptuses with large imbalances will abort. -Conceptuses with smaller imbalances will be viable, but abnormal live-born. -Risk of miscarriage in a balanced translocation carrier couple is increased, but is dependent upon particular chromosomal configuration (ranges 20-50%). What is the background population risk of miscarriage? Is there additional risk if you carry a balanced translocation? |
-->Background population risk of miscarriage in a recognized pregnancy is 15% -- 5-35% additional risk of miscarriage if you carry a balanced translocation
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What kinds of deletions are there?
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1. Terminal deletion
2. Interstitial deletions 3. Ring chromosomes Define each! |
Terminal deletion
-->Single break in the p arm or the q arm and you lose the rest of the material -->Any piece of chromosome material that is not attached to a centromere is not going to be stable in meiosis or mitosis. It will be lost -->If you terminal translocation that other little piece, unless there’s another sticky end for it to stick onto, is going to be lost and you end up with a terminal translocation Interstitial deletion -->Involve two breaks – both in the p arm or both in the q arm -->The middle segment comes out and the bottom piece rejoins the part that has the centromere, just the middle segment is lost Ring chromosomes -->Formed when you lose the end of the P arm and the end of a Q arm -->Again, you have these two ends that have no centromeres – they are LOST -->Then you have this big thing with a centromere with two sticky ends -->The sticky ends stick to each other and form a ring -->A ring is basically a specialized type of deletion -->The thing about a ring is that it doesn’t go through mitosis very well – it doesn’t replicate well, it gets lost, it doubles itself -->Individuals with ring chromosomes have more problems than you would expect solely from the loss of the genes on the ends of the p and the q terminus -->They also have problems because of the inability to go through mitosis well |
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What size does a deletion have to be before cytogeneticists can see it on a karyotype?
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-By the time we can see something wrong with chromosomes it’s usually pretty big
-The number that is typically thrown around is that in cytogenetics to be able to see something as a chromosome abnormality it has to be at least 5 Mb or perhaps even bigger -Usually <5Mb deletion which can be missed by G-band studies What are some examples? What do you call these examples that are missed by G-banding studies? How can you see them if you can't see them by G-banding? |
MICRODELETION SYNDROMES:
Things that are less than 5 megabases which you can see with specialized methods Such methods include a. high resolution chromosome analysis b. FISH c. array CGH _____________________________ Examples: Prader-Willi / Angelman 15q11q13 Retinoblastoma 13q14 William 7q11.23 DiGeorge/Velocardiofacial 22q11.2 |
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Are chromosomes one length all the time?
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NO!
-People figured out how to get really long chromosomes – high resolution chromosomes -Basically if you look at a slide of metaphases, there are going to be metaphases that are very short and very long -There are different substages within metaphase -In interphase, chromosomes are extremely decondensed and very long -Basically what’s happening as you go through the cell cycle is that they get shorter and shorter and shorter and then in anaphase is where they get shortest -What you see here is chromosome four – these (?) are closer to prophase where they’re still quite long and these are 4 closer to anaphase where it’s getting quite short -Somebody figured out how to get longer chromosomes more routinely so that we could see small deletions and small duplications with some degree of accuracy -This is called high resolution analysis ___ If you were to order a chromosome analysis and you were to look for something like DiGeorge syndrome of Prader-Willi, what would you order? What if you were looking for trisomy? |
-If you were to order a chromosome analysis and you were to look for something like DiGeorge syndrome of Prader-Willi, until a few years ago you would have asked for high resolution karyotyping. Now we have array CGH (chromosomal microarray) as the preferred technique.
-If you’re looking for trisomy, you don’t need high resolution analysis, you just need to be able to count chromosomes -If you order a karyotype and you don’t specify, you’re going to get a routine karyotype which is fine because you can always follow up with a chromosomal microarray |
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What are isochromosomes?
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-Another structural abnormality of the chromosomes
-Here remember in mitosis or meiosis should be splitting so that one goes in one direction and the other in the other direction -What if it splits transversely so that both p arm pieces go one place and both q arm pieces go in one place? Bad news bears -When that opens up and you go through replication you have two p arms and two q arms joined together with a centromere inbetween – this is an isochromosome What is the most common isochromosome? Give a disease that can be caused by isochromosomes! |
-The most common isochromosome is Xq
****46,X,i(Xq) is second most common karyotype leading to Turner syndrome phenotype**** -->Turner Syndrome : karyotype typically 45, X -->BUT there is actually a significant percentage of females who have a phenotype like turners who have a karyotype of 46X with an isochromosome of Xq -->They have 3 copies of Xq and one copy of Xp which tells you that by and large the turners phenotype is caused by loss of Xp in a female -->There is slight slight differences in the phenotype, but by and large they are indistinguishable |
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What are inversions?
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Inversions
A. pericentric B. paracentric |
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What are pericentric inversions? Paracentric?
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A. Pericentric
-Peri = around -It’s around the centromere -Have a break in the p arm and a break in the q arm and that piece with the centromere flips and reinserts itself -Now genes formerly in the p arm are in the q and genes formerly in the q arm are in the p -All the genes SHOULD be there! -This is considered a balanced structural rearrangement B. Paracentric -Involves two breaks in the p arm or two breaks in the q arm -Does not involve the centromere when it flips and reinserts itself ____ What are carriers of each type at risk for? Is the abnormal chromosome viable? |
-Carriers of either type of inversion are at risk of having offspring with duplication AND deletion of parts of the chromosome involved (known as a “recombinant” chromosome).
-In the case of a paracentric inversion carrier, the abnormal recombinant is almost never viable. |
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What are the general rules according to the International System for Cytogenetic Nomenclature (ISCN)?
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Normal female: 46, XX
Normal male: 46, XY 1. First, give total number of chromosomes per cell 2. COMMA 3. Next, give the sex chromosome constitution 4. COMMA 5. Then, describe any additional, missing or rearranged chromosomes eg. 47,XY,+21 (trisomy 21 male) 47,XXY (extra X in male; Klinefelters) 46,XX,del(5)(p12)(deletion 5p in female) -What she didn’t go through in detail is that each chromosome band is numbered, starting at the centromere, and the numbers get bigger as they go outwards to the telomeres so there is a deletion in 5 p 12 and a lab out in california will know what she’s talking about -If you have an individual with an extra sex chromosome, you string it in here with the extra sex chromosomes |
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Why would you elect to do chromosome analysis? What types of individuals? What types of clinical scenarios?
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1. Recognized cytogenetic syndrome
-->Eg. DiGeorge syndrome – characterized by heart defects, abnormal thymus, etc 2. Unrecognizable syndrome with at least 2 malformations -->For something to be cytogenetically abnormal and visible, it’s going to affect a lot of genes so there will be a lot of problems with these children 3. Ambiguous genitalia -->Might be a sign of a sex chromosome abnormality 4. MR or developmental delay in children who are dysmorphic or have multiple congenital abnormalities (MCA) 5. First degree relatives (siblings) of persons with structural chromosome abnormalities -->If you saw a baby or a child in the nursery that had a structural abnormality the first question you would have to ask is what do the parents karyotypes look like? If the parents have a balanced form of that rearrangement, then you have to ask what do the siblings look like – both the siblings to the parents and the siblings to the child with the unbalanced karyotype 6. Stillborn infants with malformations or with no recognizable reason for fetal death -->Stillborn infants have very high rates (~5%) of chromosome abnormalities 7. Females with proportionate short stature and primary amenorrhea -->Think about Turner syndrome 8. Males with small testes or significant gynecomastia -->Think about klinefelter syndrome or XXY |
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What is mosaicism?
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-Presence in an individual or a tissue of at least two cell lines, which differ karyotypically, but are derived from a single zygote.
-Severity of phenotype is dependent upon: ???? |
1. Frequency of the abnormal cell line
-->Expect that if an individual has 75% trisomy 21 cells than an individual that has 25% trisomy 21 cells 2. Tissue distribution of the abnormal cell line -->Just because you have 25% trisomy 21 cells in the blood doesn’t mean that this is truly reflective of what is going on in the brain or in the heart or other organs you aren’t testing |
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Is a person with Down syndrome mosaicism, what do you expect to see?
How did they become mosaic in the first place? |
-Down syndrome mosaic:
-->Some cells are trisomy 21 -->Some cells are normal -They are all derived from a single zygote – not a chimera where you have two different zygotes that fuse -A mosaic starts out as a single fertilized egg but there are two different cell lines that can occur, possible due to nondisjunction -We don’t know the extent to which mosacism ameloriates the trisomy because we arent sampling those other tissues |
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If you take a blood sample and you don't see mosaicism, are you in the clear that your patient is in fact not a mosiac?
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-Can be such that you look at the blood and you have a good representation of what’s happening in the rest of the body, or it could be fairly compartmentalized
-This is why a really keen eyed clinical geneticist may want to look at skin -They do the blood, don’t find the abnormality they expect, so they may do a skin biopsy and find something -Sometimes its even such that the skin may be lightly pigmented and darkly pigmented and you can biopsy both the light and the dark and one is abnormal and the other is normal |
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How often does mosacism occur?
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-0.1% is probably a slight underestimate because when they did these cells they didn’t count enough cells
-If you karyotype the 1st cell on most people it should tell you the whole story, but to be sure you do 20, 50 or more. Sometimes you come across a 2nd cell line that can have phenotypic effects Why is there a difference / why is it higher for CVS and amniotic fluid? |
-Amnio is probably pretty close to the real thing, although it may be a little higher – the real number is probably between 0.1-0.25%
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Why does CVS give such high percentages of mosaicism?
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-In CVS, we’re sampling the placenta
-When you’re sampling the placenta, you aren’t sampling the baby itself -There can have been a mutation that occurred in the placenta that is completely confined to the placenta -We find 1-2% of the time crazy trisomies in the CVS that we don’t find in the fetus! -->Trisomy 10 and stuff like that The term is Confined Placental Mosaicism |
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What is confined placental mosaicism?
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-Discrepancy between placental and fetal karyotype
-More widely recognized after advent of CVS -Detected in 1.5-2% pregnancies by CVS -~20% of pregnancies with idiopathic IUGR for no known reason actually have confined placental mosaicism -->Placenta has a chromosome abnormality that is not supporting the baby as well as it should; therefore the baby is small -->When you see a small baby with no other reasons, maybe the karyotype of the placenta is not normal |
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What different forms of confined placental mosaicism can you see?
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-This is what confined placental mosaicism can look like
-If you did a CVS and you find mosaicism (say the dark cells are normal and the light cells are abnormal) -You would expect that if you sample that placenta by CVS and you find mosaicism you would hope it’s reflective of the fetus BUT -Sometimes you can find mosaicism in the placenta and the fetus is completely normal – false positive CVS result -Sometimes you can find a normal placenta or CVS result and a mosaic fetus – false negative CVS result -Fortunately this is pretty rare, but it does happen -This is why most cytogeneticists are not fans of CVS -->If you find a mosaicism, most of the time they are unusual things you wouldn’t see in the fetus -->Then you have to tell the patient they have to wait until you can do an amniocentesis and then maybe you can figure it out from there |
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What are the mechanisms for the formation of mosaicism?
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2 main mechanisms
1. Can occur in mitosis -If it happens in mitosis, we aren’t talking about an increased incidence due to advanced maternal age -This can happen as easily in a 25 year old as in a 45 year old -Nondisjunction in the developing fetus CAN happen, just as it can happen in meiosis -You can have nondisjunction in mitosis where one cell ends up being monosomy 21 and one daughter cell ends up being trisomy 21 -The monosomy cell is not going to be viable (this will end right there) -The trisomy 1 cell WILL be viable and produce other trisomy cells -Meanwhile, you have all these other normal cells over here carrying on and producing normal cells -You can get a mosaicism for a normal cell line and a trisomic cell line -You would expect in this case that the normal cell line would be in a greater frequency than the abnormal cell line, but it depends on which cells mutated and where it -ends up in the developing embryo -Alternatively, if that happens with a sex chromosome abnormality, you can have a monosomy X which is viable -->Here the monosomy is viable as is the trisomy, so you’d actually end up with 3 cell lines -- a mosaicism for 45,X, 46,XX, and 47,XXX. -->This is due to mitotic nondisjunction 2. you start out with a meiotic nondisjuntion error -Start out for example with a trisomy 21 probably due to a meiosis I error -Then as these are going through mitosis in the developing fetus, one of the 21s does not get incorporated into the nuclear membrane as its reforming – this is called ANAPHASE LAG – it just kind of lags behind and doesn’t get incorporated -The cell back-mutates to normal -In the midst of all these abnormal cells you have a small line of normal cells -This is called TRISOMY RESCUE when you have anaphase lag -In this case, you would expect that the majority of your cells are trisomic and the minority of your cells are normal |
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What is uniparental disomy?
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-Presence of a disomic cell line containing two chromosomes of a given kind, inherited from only one parent.
-You would expect biparental inheritance for any set of chromosomes – one that you get from your mom and one you get from your dad -There are certain rare cases where that doesn’t happen -Say you get two chromosome 7’s from your dad and none from your mom and visa versa -->That is called uniparental disomy |
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What do 1/3 of corrected trisomies result in ?
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UNIPARENTAL DISOMY!
-Think about CVS, for example, where we talked about confined placental mosaicism -You can find some unusual trisomies -What if you found trisomy 15 in a CVS and then you did the amniocentesis and you found a normal karyotype? Would you feel good about it or not? What could happen? -Say the trisomy 15 is due to a maternal meiotic nondisjunction so that this fetus with trisomy 15 has two maternal 15’s and one paternal 15 -Then we have trisomy rescue which could be a good thing or not When you have trisomy rescue, you have three possibilities: 1. One of the maternal 15s is lost, and you have still normal biparental inheritance in the fetus 2. The other maternal15s is lost and you have normal, biparental inheritance in the fetus 3. This 15 is lost and now you have uniparental disomy MATERNAL. You have two 15’s from the mom and none from the dad Do we care? Why? |
Yes. Because of imprinting.
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What is genomic imprinting?
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-Imprinting is a reversible change in the genetic material that causes changes in gene expression
-Doesn’t happen in the entire genome -Only happens in certain parts of the genome on certain chromosomes, such as chromosome 15, 6, 7, 14, 11 (there are about 6 where imprinting matters) -->If you inherit both of your mother’s chromosomes 1 and none from your dad, because there is no imprinting it shouldn’t make a difference as long as you aren’t inheriting any true chromosome abnormalities -->If she has normal chromosomes 1 and you just get uniparental disomy from your mom for a nonimprinted chromosome, it shouldn’t make any difference -Differential expression depending on parental source -Maternal and paternal chromosomes can function differently and can influence the expression of human genetic disorders. -Modification of DNA during critical period -Modification temporarily changes gene expression -Contrary to basic Mendelian principles. -If its an imprinted chromosome where there is a change in the gene expression depending on whether the parent is male or female or whether certain genes are turned on or off, it will make a difference |
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Name two classic examples of imprinting!
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Angelman and Prader-Willi Syndromes: similar deletions, different syndromes
-In angelman syndrome, the phenotype is more specific (left hand side) -Prader-Willi phenotype (right side) is slightly less severe although these are both severe and they both involve deletions of chromosome 15 |
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What is the Molecular basis for Prader-Willi syndrome (PWS) and Angelman syndrome (AS) ?
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-70% of the time if you see Prader-Willi, it is going to be due to an interstitial deletion of chromosome 15
-->The chromosome 15 that is going to be deleted is going to be the one that the FATHER passed on -70% of the time if you see Angelman syndrome, it is going to be due to an interstitial deletion of the maternally derived chromosome 15 -->This is due to the fact that there is differential gene expression depending on whether your mom passed on the 15 or your dad -In another percentage of Prader-Willi and Angelman, this can be due to uniparental disomy -Another way of getting both of these syndromes is to have uniparental disomy -->Prader-Willi is a deletion of 15q -->If you have two maternal 15’s, you have, in essence, a deletion of paternal 15 --> leads to Prader-Willi syndrome -->If you have two paternal 15’s, that will result in Angleman syndrome because you have loss of the gene expression you would get if you had a maternal contribution |
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What are chromosomal microarrays?
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Chromosomal Microarrays Aka Array CGH
-With a microarray, these are slides that are analyzed by scanner -These slides have little spots of short sequences of DNA on them that cover the entire genome -These short sequences are segments that tile all the way through the genome -You can hybridize the DNA from your patient to the microarray plate |
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What can a chromosomal microarray tell you?
What can't a chromosomal microarray tell you? |
The array will tell you things you cannot see by chromosomal analysis:
1. Copy number GAIN – Trisomy, duplication 2. Copy number LOSS – Monosomy, deletion What it CANNOT tell you is about a balanced structural abnormality, but it can tell you about unbalanced stuff -This is an individual who was diagnosed eventually with this “Nablus mask-like facial syndrome” -They did a microarray, but if you look at the blue tracing which shows chromosome 8, it shows a loss of material that was 3 Mb (by eye, she cant see anything less than 5 Mb) -Not only does it tell you the number of Mb and that it was bands 8q21 and 8q22, it also tells you exactly the NUCLEOTIDES that are involved -We number our nucleotides from #1 and then they get bigger as you go down the chromosome -In this individual, it was nucleotide (see slide) that was deleted -This gives us more power than just saying a particular band was deleted What do we do when we see something like that? |
-What we do when we see something like that is we have these databases like the UCSC Genome Browser that has the genes in it so you can put in your nucleotide sequence and what you can see is exactly which genes are in the deleted region
-Now we’re talking about particular genes -From there we can find out which genes have known syndromes associated with them -We can go and look at the known online mendelian inheritance in man and find out what abnormalities are associated with them -We can now find out which genes are essential for a particular syndrome to be caused |
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What was the cool thing about this paper "Consensus Statement: Chromosomal Microarray Is a First-Tier Clinical Diagnostic Test for Individuals with Developmental Disabilities or Congential Anomalies?"
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-There was a game changing paper (!!) that came out two years ago
-Consensus of an international group of cytogeneticists that talks about chromosomal microarray -She read the red underlined part -NOW we can see down to the exon level of a gene that is deleted! |
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