Cytogenetics Flashcards

Question

How are chromosomes classified

Answer 1

dependent on the size of the chromosome, banding pattern, and position of the centromere p=short arm, q=long arm

Answer 2

centromere in the middle of the chromosome, equal amts of genetic material on each side ex:chrom 1

Answer 3

centromere off-centered, less material on the p arm, more material on the q arm

Answer 4

centromere at the top of the chromosome, virtually not material on the short arm (only satellite material- for ribosomal RNA production) chrms 13, 14, 15, 21, 22

Answer 5

can only visualize gains, loses, and rearrangements in chroms chromosome stretches and more bands= greater resolution (but have more overlap, harder to visualize) @ 850 level, 1 band =50-100 genes ideal resolution for blood/amnio is 550 resolution; ideal for bone marrow is 400

Answer 6

45,X, with a translocation of p11 on chromosome 2 to chromosome 4 and a translocation of q13 from chromosome 4 to chromosome 2 AND another translocation of p13 from chromosome 7 to chromosome 21 and a translocation of q12 from chromosome 21 to chromosome 7

Answer 7

use of fluorescent molecules (labeled DNA probes) to detect a particular chromosome, gene, or chromosome region with a specific complementary sequence visualized with fluorescent microscope if a probe lights up, the gene is present; if nothing lights up, the gene is not present MUST BE LOOKING FOR A SPECIFIC ABNORMALITY ON THE CHROMOSOME can get resolution as great as 2-5 genes/probe, but probe needs to be highly specific

Answer 8

a cell population derived from a single progenitor cell needs to meet at least one of the following criteria: at least 2 cells that have a gain at least 2 cells with the same structural rearrangement (del, add, t) at least 3 cells that have the same numerical aberration (much easier for a chromosome to be lost than gained)

Answer 9

looking at 200 interphase chroms in the nucleus, only can visualize exactly what you are probing for, don't get any other info for the other chroms used for cancer. ex: Abl on chrom 9 and BCR on chrom 22 for chronic myelogenous leukemia, if they co-localize (in the form of a translocation), FISH will light yellow to indicate over lap of red and green probes

Answer 10

measures gains and losses of DNA, can visualize up to 2.5mil bp (~15-30 genes) but usually need a minimum of 5 million bp use for microdels, CNVs, but CANNOT DETECT BALANCED REARRANGEMENTS better resolution than karyotype

Answer 11

a two way exchange of material between 2 chroms. a break occurs in one arm of each chrom involved, breaks switch position

Answer 12

reciprocal, exchanges are equivalent, no loss of genetic material

Answer 13

partial trisomies and monosomies, loss or gain of some genetic material

Answer 14

one of the translocation segments is small (in the telomeric region) ex: t(1:4)(q44;q43.3) may have no effect on phenotype or some effect

Answer 15

both translocated segments are large; translocations at breakpoints at or within a centromere exchanging entire arms are called whole arm translocations individuals with balanced exchanges are phenotypically normal, problems arise when they try to reproduce

Answer 16

1. 2:2- 2 chromosomes to one cell, two chromosomes to the other (typical) 2. 3:1- 3 chromosomes to one cell, one chromosome to the other 3. 4:0- all 4 homologs go to one cell method of segregation is dependent on the size of the translocated segments

Answer 17

one centromere goes to one pole, the next goes to the other pole (each centromere goes alternately to one or the other pole) daughter cells are normal/balanced only mode that leads to gametes with a complete genetic compliment (2:2 segregation)

Answer 18

unlike centromeres travel together (ONE is UNlike centromeres) the most common form of malsegregation ex: chromatin on the long arm of chrom 11 is translocated to the tip of chrom 3 on the short arm, while the telomeric tip of chrom 3 on the short arm has moved to chrom 11 gametes will be: partial 11q trisomy, partial 11q monosomy (2:2 segregation)

Answer 19

like centromeres travel together relatively uncommon typically limited to t's where each chrom has a short arm with little genetic content and can be viable in the trisomic state (most commonly involves 9p and a D or G chrom (D: 13, 14, 15; G: 21,22)) breakpoint usually between the upper long arm of one chrom and immediately below the centromere in the other chrom; the LEAST IMBALANCED, LEAST MONOSOMIC GAMETE WILL BE VIABLE most cause a lethal imbalance during early embryogenesis (2:2 segregation)

Answer 20

gametes with 24 and 22 chromosomes are formed conceptuses have either 47 or 45 chroms

Answer 21

3:1 segregation trisomy: two normal chromosomes and one translocated chromosome move together (the centric portion contains the whole short arm of the derivative chromosome); most abnormal offspring have a tertiary trisomy; ex: der(22)t(11;22)(q23;q11) monosomy: rare, if one der is very small and the amt of material missing is "monosomically small" there may be a viable conceptus (such as missing a subterminal portion)

Answer 22

3:1 segregation full autosome trisomy or full monosomy trisomy: two translocated chroms and one normal chrom move together; more severe outcomes, less frequent only chromosomes 13, 18, 21, and 22 are viable trisomies monosomy: only observed in PGD, likely very early arrested development of the embryo

Answer 23

results in a double trisomy or a double monosomy total nondisjunction of quadrivalent complex is never viable

Answer 24

1. assume alternate segregation is frequent and associated with phenotypic normality 2. the least imbalanced, least monosomic gametes are most likely to produce a viable conceptus 3. if the translocated segments are small in genetic content, adjacent 1 segregation is most likely to give rise to a viable, abnormal offspring 4. if the centric segments are small in genetic content, adj 2 segregation is most likely to produce a viable, abnormal outcome 5. if ONE chromosome in the quadrivalent is small in content, 3:1 segregation is most likely (the small chromosome could be a derivative OR chroms 13, 18, or 21) 6. if the quadrivalent has properties of rules 3 and 5 OR 4 and 5, both adjacent and 3:1 segregations could give rise to a viable conceptus 7. If the translocated and centric segments are large in content, NO viable offspring are possible 8. If the translocated segments are BOTH subtelormeric, pairs may just join as bivalents (no quadrivalent) and segregate independently

Answer 25

large: nonviable moderate: a miscarriage or later fetal death lesser: abnormal live birth (single segment imbalances from adjacent 1 segregation are usually the only viable conceptus

Answer 26

61% of nonviable fetuses came from a translocation carrier mother and only 39% came from a carrier father background pop risk for spontaneous abortion is 15%; the risk for a balanced t carrier ranges btwn 20-30% - risk depends on the size of the chromosome segment couples with three or more miscarriages should undergo karyotype (some male carriers may be infertile due to arrested spermatogenesis)

Answer 27

mode of ascertainment predicted type of segregation leading to potential viable gametes sex of transmitting parent (mom more likely to pass on vs dad) assessed imbalance of the potentially viable gamete risk is ~25% for carriers to have an unbalanced fetal karyotype at amnio when there was a previously abnormal child if the same balanced t is seen in a parent, there is NO INCREASED RISK for abnormality in rare familial t's, the rearrangement may promote mitotic malsegregation and disrupt a tumor suppressor gene, leading to increased cancer risks

Answer 28

change in the level of gene expression caused by a change in a position of the gene relative to where it is normally found

Answer 29

chromosome 3 t's, 5q, 11q, and 17p

Answer 30

involves the acrocentric D and G group chromosomes. the t chromosome has 2 fused long arms and no short arms heterologous t's can pass through generations whereas homologous t's are usually de novo (rare) written as: 45,XX,der(14;21)(q10;q10)

Answer 31

Rob(13q;21q) / Rob(14q;21q)

Answer 32

1. centric fusion: fusion at the centromere forming a monocentric chromosome 2. union following breakage in one short arm and one long arm: essentially a whole arm reciprocal t, resulting in a monocentric chromosome 3. unition following breakage in both short arms: results in a DICENTRIC chromosome

Answer 33

fusion in the zygote of mat and pat homologs can also result from an isochrom during meiosis

Answer 34

nullisomic egg is "rescued" by reduplication of paternal homolog, leading to paternal UPD

Answer 35

possibly due to specific homologous, but inverted, segments in these chromosomes (homology encourages crossing over)

Answer 36

2:1 segregation alternate segregation will produce normal and balanced gametes adjacent segregation produces two types of disomic gametes and nullisomic gametes

Answer 37

males: translocation malsegregants are seen more often in men with oligospermia; in male carriers, t DS and t T13 are rare females: have a ~20% risk for abnormal offspring; children of female carriers of rob's have a ratio close to 60:40 for the balanced rob compared to the normal karyotype

Answer 38

can be corrected due to mitotic loss of one normal homolog: results in UPD UPD does NOT affect phenotype outcomes for chroms 13, 21, and 22 UPD DOES have imprinting effects for chroms 14 and 15; RARE; at prenatal dx, all balanced chromosome 14 and 15 Robertsonians need UPD analysis

Answer 39

typically results from a nullisomic ovum rescue occurs by replication of the paternal homolog, resulting in uniparental paternal isodisomy (RARE)

Answer 40

due to the fusion of two paternal homologs (biparental inheritance) due to a rearrangement of an isochrome where each long arm is the exact copy of the other, resulting in UPD Only disomic and nullisomic gametes are possible NO VIABLE GAMETES ARE POSSIBLE

Answer 41

associated with translocation DS resulting from adjacent segregation in female heterozygotes, the risk of an affected fetus with translocation DS is ~15% at amino the risk for a liveborn is ~10% In male heterozygotes, the risk of an affected fetus with translocated DS is 1% at amnio

Answer 42

rare risk is ~1% for t T13

Answer 43

female risk is ~15% to pass to a fetus at amnio male risk to pass on rob is less than 1% at amnio and liveborn

Answer 44

risk is less than 1% for both males and females

Answer 45

risk for a liveborn is 10% in females and 1% in males

Answer 46

rob(14q;15q); rob(14q;22q); rob(15q;22q)

Answer 47

around the blastocyst stage, lyonization occurs (~2wks post fertilization). One X chromosome in every cell of a female conceptus is randomly genetically inactivated "dosage compensation" allows for the functional monosomy for most of the X chromosome (all progeny cells will have the same X inactivated, making the female a true mosaic

Answer 48

Where X inactivation occurs, Xq13 and spreads in both directions along the chromosome within the XIC is the XIST, a cis-acting gene that is only transcribed on the INACTIVE X chrom; functions by coating the entire chrom to prevent transcription, possibly by methylation/acetylation of DNA and chromatin folding not all genes are inactivated- some loci are disomic; inactivation is blocked at Xp22.3, aka the pseudoautosomal region (PAR1), which pairs with Yp during meiosis; PAR2 in Xq and several other genes also remain active

Answer 49

The der(x) has the XIC and is inactive The der (autosome) is active (for balance, both parts of the X chromosome involved in the translocation must be active; the "normal" X chromosome will be NONRANDOMLY inactivated in most cells) you would rather have a balanced autosome rather than a monosomic autosome

Answer 50

INACTIVATION FAVORS THE LAST UNBALANCED CONCEPTUS. It results from non-random activation of the abnormal X This can only occur if the abnormal X has an XIC; if the der(X) has a large autosomal translocated segment, then the normal X will be nonrandomly inactivated (to prevent monosomy of an autosome) If the der(X) has no XIC, the X chromosome CANNOT be inactivated --> results in a partial X disomy

Answer 51

t's can disrupt genes associated with specific Mendelian conditions when the normal X is inactivated due to a large autosome t, there is NO FUNCTIONAL COPY of the normal allele ex: females with an Xp21-autosome t with DMD/BMD

Answer 52

without intervention are infertile due to spermatogenic arrest

Answer 53

SRY, the testis determining gene is on Yp in PAR1 genes on Yq needed for reproduction are AZFa, b, and c ~1/2 of Yq has the genetic inactive heterochromatic region Y chrom translocation (other than to an acrocentric chrom) could also cause sterility (but otherwise, normal male)

Answer 54

no gain or loss of euchromatin and phenotype is normal ~50% involve chromosome 15 (bc close homology between 15p and Yq heterochromatin, favoring the t)

Answer 55

SRY on Yp could be translocated to an autosome associated with azoospermia and a Turner-like phenotype ex: dic(Y;22)(q11.23;p11.2), dic(Y;15)(q11.2;p11.1)

Answer 56

Distal Xp is deleted with the loss of PAR1 (Xp genes= ARSE, SHOX, STS, KAL, MRX) In males, loss of these regions can be detrimental The X chromosome with the most genetic imbalance is usually inactivated. Since the most genetically stable is active, inactivation IS NO LONGER A RANDOM EVENT

Answer 57

partial monosomy Xp Typically fertile with normal development

Answer 58

nullisomic for Xp usually the son of a t(X:Y) mother if the breakpoint is DISTAL intelligence will be normal if the breakpoint is PROXIMAL (containing a lot of genes) there will be mental delay most males are infertile, the majority of these cases are familial

Answer 59

46,X,der(X)t(Xp;Xq) results in a del dyp of Xp/Xq or vice versa results from unequal crossing over between the two X chromosomes in the oocyte could also occur when an X chromosome folds onto itself (origin is probably paternal in this case) will present with pubertal and menstrual abnormalities, as well as infertility

Answer 60

~50% of female and almost all male carriers are infertile fertile females are at risk of having abnormal offspring ranges from mild (XO/XXY) to severe (partial X disomy or autosomal aneuploidy) each t needs to be assessed individually, dependent on which pieces are involved

Answer 61

partial turner, partial KS, and partial XXX syndromes a single segment translocation with a small X segment could have the above AND a functional disomy for distal Xp or Xq

Answer 62

has a risk for partial autosomal monosomy or trisomy any 2-2 unbalanced segregants (likely adj-1for the least amt of imbalance) from a double segment translocation has a combined deldup risk (since there is not much material or too much, SAB is likely)

Answer 63

a female fetus with the same t may not have the same phenotype as mom (X inactivation may be different, resulting in partial X disomy) male carriers range from normal phenotype to offspring with major genital defects (u/s recommended to look for the presence of typical male genitalia)

Answer 64

in the apparently balanced: male risk for infertility must be assessed based on t breakpoints (can do ICSI, IVF, and PGD) for those with Yq and actocentrics: no clinical significance (very minor risk of T15 with corrected to UPD if t(Yq;15p)) Cryptic 45,X,t(Yp-acrocentric): stable and phenotypically normal

Answer 65

Female offspring are typically fertile and of typical intelligence (50% chance of having offspring with the translocation) male offspring may be abnormal depending on the loci involved (almost always infertile, offer ART)

Answer 66

associated with infertility in small imbalances when fertility is possible, daughters will have same phenotype as mom male pregnancy would most likely miscarry due to X nullisomy/disomy (if del/dup is small, it may be viable, but with major phenotypic abnormalities) offspring with the normal X would be unaffected

Answer 67

an intrachromosomal structural rearrangement in which a chromosome is reversed end to end; a single chromosome undergoes breakage and rearrangement within itself

Answer 68

involves the centromere; break in the short AND long arm (more phenotypic consequences)

Answer 69

no centromere involved; breaks in either the short OR long arm

Answer 70

heterozygotes may produce unbalanced gametes due to recombination within inverted segments during meiosis inversion homolog and normal homolog do not match perfectly; therefore, and inv loop is formed to align the segments of both homologs. results in: 1. normal homolog (aa') 2. inverted homolog (bb') 3. a recombinant homolog (cc'dup(p)- a dup of part of the short arm and del of part of the long arm) 4. a recombinant homolog (dd'(dup(q)- a dup of part of the long arm, del of part of the short arm)

Answer 71

heterozygotes with distally large inverted segments CANNOT have viable abnormal offspring 46,XY,rec(7)dup(7q)inv(7)(p.14q36.3) partial trisomy 7q, monosomy 7p 46,XY,rec(7)dup(7p)inv(7)(p.14q36.3) partial trisomy 7p, monosomy 7q mosaicism for a balanced inv rarely occurs

Answer 72

forms the same way as autosome inv breakpoints in the X critical region may influence the phenotype in females imbalances in the 46,X,rec(X) females may be "corrected" by selective inactivation of the abnormal X 46,Y,rec(X) will have partial X nullisomy and functional X disomy can be transmitted by both males and females

Answer 73

appear normal breaks in the X critical region (q13-q22/q22-q26) can cause gonadal dysfunction (primary amenorrhea, premature menopause) ovum with a recombinant X has different outcomes depending on the X or Y bearing sperm x bearing sperm: del(Xq)/dup(Xp): normal or tall stature, ovarian dysgenesis; del(Xp)/dup(Xq): short stature, normal ovarian function y bearing sperm: nullisomy for the deleted X segment. results in major congenital anomalies and neurodevelopmental compromise; disomy also results in major deleterious effects

Answer 74

no effect on phenotype or reproduction because there is no recombination in the inv segment during meiosis all daughters are heterozygous; sons receive mom's normal X

Answer 75

common, considered a normal variant and has no phenotypic or reproductive effects

Answer 76

heterozygotes whose family had a recombinant child heterozygotes for an inversion heterozygotes with inversions involving chrms 13, 18, and 21 molecular analysis for the invs involving chroms 15q11-q13 to r/o PWS and AS

Answer 77

normal, inverted, acentric, and dicentric chroms (acentric and dicentric gametes are nonviable) therefore, heterozygotes cannot produce unbalanced offspring (will produce normal or balanced zygotes) genetic risk factor for abnormal offspring is VERY SMALL

Answer 78

In utero exposure to sex hormones Random developmental variation (mom/dad with ambiguous genitalia) Chromosomal and genetic anomalies

Answer 79

x chromosome aneuploidies are typically associated with "little" phenotypic abnormality due to dosage compensation however, some loci on additional X chromosomes are still active, leading to mild phenotypic abnormalities in females with abnormal X's, X-inactivation is usually non-random (if the abnormality is a microdel/dup, the inactivation pattern may be RANDOM)

Answer 80

deletion of Xp and Xq (or dup of both) if the XIST is missing, an abnormal phenotype will occur (FUNCTIONAL X DISOMY)

Answer 81

loss of one arm of the chromosome and replacement of it with an exact copy of the other arm

Answer 82

mosaic trisomy 8 and 9

Answer 83

4-5% from a parent with a 45,XX,der(14;21)(q10;q10)

Answer 84

nonviable, intrauterine pregnancy with an empty gestational sac OR a gestational sac with an embryo or fetus with no heart activity in the first 6-7wks of gestation

Answer 85

10% or 1 in 10

Answer 86

caused by polyspermy/dispermy usually spontaneously abort when extra chromosome complement is maternal (digynic): fetus with IUGR, very small placenta when extra chromosome complement is paternal (diandric): well grown fetus, large cystic placenta

Answer 87

inheritance of both homologs from the same parent most UPD pts have: Intrauterine and post natal growth delay, mental disabilities, congenital malformations, and dysmorphic features could also result in homozygosity for an AR gene

Answer 88

KARYOTYPES ARE NORMAL can only be demonstrated at the molecular level

Answer 89

both homologs are identical polymorphic DNA markers show both homologs with the same haplotype (group of alleles inherited from a single parent) from one parent results from nondisjunction in MeII or a mitotic error

Answer 90

homologs are different polymorphic DNA markers show the two chromosomes have the same haplotypes as the chromosome pair from one parent results from nondisjunction in MeI

Answer 91

only part of the chromosome comes from the same parent --> is the result of crossing over

Answer 92

same genotype will produce a different phenotype depending on the sex of the transmitting parent (ex: methylation as an imprinting mechanism) imprinted DNA segments function monoallelically (either maternal or paternal segment will be active; if both segments originate from one parent there will be DOUBLE the amount of expression OR no expression, leading to the phenotypic defects in UPD IF THE CHROMOSOME IS NOT SUBJECT TO IMPRINTING, UPD HAS NO EFFECT

Answer 93

for all 46 chromosomes, forms a complete hydatidiform mole one maternal and two paternal chromosome complements produces a triploid fetus

Answer 94

for all 46 chromosomes, forms a benign cystic ovarian teratoma one maternal and two paternal chromosome complements produces a triploid fetus

Answer 95

gamete complementation trisomic rescue monosomic rescue mitotic error two abnormal events must occur simultaneously OR sequentially in the above: 1. errors can be both meiotic 2. meiotic followed by mitotic 3. both mitotic 4. the original abnormality is sporadic (no recurrence risk) ONLY RISK is AMA, meiotic nondisjunction leading to UPD

Answer 96

one parent produces a nullisomic gamete and the other produces a disomic gamete

Answer 97

CAUSES THE MOST UPD trisomic early conceptus will lose one of the extra chromosomes restores the disomy if the "wrong" chromosome is lost, the zygote will have either mat or pat UPD

Answer 98

if a nullisomic gamete is produced at meiosis, the conceptus will be monosomic mitotic correction replicates the normal homolog producing UPD isodisomy

Answer 99

occurs in a typical conception leading to trisomy or monosomy in trisomy: the "wrong" chromosome is lost producing either mat or pat UPD in monosomy: the chromosome is duplicated

Answer 100

can arise by post-zygotic somatic recombination (UPD segment is distal; rest of chromosome will have typical biparental inheritance) can also arise by meiotic nondisjunction producing a disomic gamete causing a trisomic conception to occur leading to mitotic crossing over between a mat and pat chromatid resulting in one of the chromosomes being loss (trisomy rescue) will have an effect if the chromosome has loci subject to imprinting

Answer 101

12, 18, and 19

Answer 102

caused by the absence of activity of the genes in 15q11-13 under control of SNRPN deletions cause ~70% (removes about 4Mb in 15q11-13, encompasses the PWS and AS structural genes and the IC) can also result from passing an unbalanced t OR inversion of chrom 15 (ALWAYS do UPD analysis at prenatal testing) ~25% is due to UPD PWS: both chromosome 15's are MATERNAL (80% results from maternal nondisjuction in MeI, AMA associated) ~1% result from IC defects (pts have biparental inheritance with a uniparental methylation pattern and gene expression; can also be microdeletion) uncommonly, PWS results from a cytogenetically detectable rearrangement

Answer 103

AS caused by absence of activity of the UBE3A gene deletions cause ~70% (removes about 4Mb in 15q11-13, encompasses the PWS and AS structural genes and the IC) can also result from passing an unbalanced t OR inversion of chrom 15 (ALWAYS do UPD analysis at prenatal testing) 3-5% of AS reusults from UPD AS: both chromosomes are PATERNAL usually results from monosomy 15 correction of a nullisomic ovum, AMA associated 2-4% due to IC defects (pts have biparental inheritance with a uniparental methylation pattern and gene expression; can also be microdeletion) AS can also result from a mutation in UBE3A (also seen in pts with no known etiology, suspected epigenetic error)

Answer 104

Type 1: Classical del of 15q11-13 Type 2: paternal UPD 15 Type 3a: IC microdeletion Type 3b: Functional defect of IC Type 4: UBE3A mutation Type 5: no known etiology, possible epigenetic error

Answer 105

9;22 t associated with SML (small lymphocytic lymphoma/Chronic myeloid leukemia) and AML (acute myeloid leukemia) cancers

Answer 106

derivative chrom 15 has the centromere of chrom 15 end of chrom 15 has been replaced with the end of chrom 22 extra material of 22, missing material of 15

Answer 107

occurs when there is a del at both ends of the chromosome and the ends fuse symptoms due to deleted genes at terminal end features depend on the chromosome bust most include growth delay can be inherited but most are de novo

Answer 108

extra small chrom; no distinct banding pattern so need a CMA to determine what genetic info it includes/what chrom it is from can cause symptoms if it contains a region that would lead to a dup syndrome can be inherited or de novo; 1/3 are familial