Unit 2 Day 2

Question 1

balanced structural aberration

Answer 1

• normal complement of chromosomal material, no loss or gain
• reciprocal translocations
• roberstonian translocations
• inversions

Question 2

unbalanced structural aberration

Answer 2

• abnormal chromosome content
• deletions
• duplications
• isochromes (duplications short/long arm)
• marker (ring) chromosomes
• recombinant chromosomes

Question 3

Structural rearrangements require what type of breaks?

Answer 3

double strand breaks
results deletion, inversion, reciprocal relocation
occur in repeat sequences in homo/non-homo chromosomes

Question 4

reciprocal, interchromosomal exchange (translocation)

Answer 4

break in arm of each of 2 chromosomes

reciprocal exchange of segments

Question 5

balanced (apparent) translocations

Answer 5

no loss or gain of genetic material
no phenotypic effect for heterozygote
exception: breakpoint in a gene disrupting function

Question 6

quadrivalent formation

Answer 6

meiosis 1
reciprocal translocation
normal and translocated arrange to maximize sequence pairing at zytotene
form quadrivalent
segregation described by relationship of the centromeres to each other

Question 7

alternate segregation

Answer 7

centromeres of homologues go to opposite poles
leads to gametes with normal chromosomes
gametes with both derivatives (balanced)
only mode of segregation leading to gamete with full complement of chromosomes

Question 8

adjacent 1 segregation

Answer 8

abnormal segregation
adjacent centromeres go to same pole
nonhomologous centromeres
most common when translocated segments are small
results in trisomy and monosomy for translocated segments

Question 9

balanced translocation carriers

Answer 9

risk of unbalanced progeny (risk=0-30%)

maternal carriers-more likelihood of offspring with phenotype

Question 10

robertsonian translocations

Answer 10

structural chromosome rearrangement
centric fusion
joining of two afrocentric chromosomes at the centromere, short arm (satellite, repetitive sequences, no euchromatin, no protein coding, no effect)
balanced!!!!!

Question 11

phenotype of robertsonian translocations

Answer 11

most common structural chromosome rearrangement
usually no phenotype (no loss euchromatin)
risk to have offspring with unbalanced karyotype
prevalence infertile men

Question 12

most common robertsonian translocations

Answer 12

13;14=75% of all RTs (one of most common in humans)
14;21
21;21
all can be de novo and familial

Question 13

de novo unbalanced robersonian translocations

Answer 13

46 chromosomes
normal homologue+RT “homologue” (leads to trisomy 21)
RT involving 13 and 21 can lead to viable trisomies

Question 14

Trisomy 13 from Robersonian

Answer 14

20% of trisomy 13 is derived from translocation

familial and de novo (mostly de novo)

Question 15

intrachromosomal rearrangement

Answer 15

inversion
balanced (most cases)
normal phenotype (carrier, most cases)
familial-more common
up to 1% of pop

Question 16

pericentric inversions

Answer 16

inverted segment includes centromere
breaks in p and q arms
orient by rotating inverted segment, old fast the flanking segments of chromosome

Question 17

benign pericentric inversions

Answer 17

heteromorphic variants
inversions containing constitutive heterochromatin (***9qh, 16qh, 1qh, Yqh)
pericentric, g-positive bands of 19p12 or q12
almost always familial
not associated with increased SABs, infertility, or recombinant offspring

Question 18

inversions during meiosis

Answer 18

pericentric inversions form loop (during homologous pairing of meiosis)
issue-how to get maximal pairing
potential for recombinant chromosomes

Question 19

outcomes of recombination in pericentric

Answer 19

• one recombination event is predicted within the inverted segment of the inversion chromosome and homolog in chromosome
• crossover btw. 2 non-sister chromatids=2 complimentary recombinants
• duplication of long arm, deletion short arm flanking segments (vice versa)

Question 20

metotic recomb in inversion carriers

Answer 20

• possible gametes: normal unrearranged; inversion, balanced (these 2 are 50%)
• two complementary recombinants (one loveborn, one lethal)

Question 21

rec 8

Answer 21

term infant
appropriate size
hispanic descent alamosa
VSD
hypertelorism, thin upper lip wide face

Question 22

inversion 8 carriers

Answer 22

recurrence risk 6.7%

Question 23

paracentric inversions

Answer 23

inversion segment excludes centromere
2 breaks w/in same chromosome arm
difficult to detect
familial and sporadic
turner syndrome variant, Xp/q inversions

Question 24

chromosome 22 rearrangements

Answer 24

mediated by segmental duplications

deletion or duplication can result in same phenotype

Question 25

epigenetics

Answer 25

mitotically and meiotically heritable variations of gene expression that are not caused by changes in DNA sequences.

Question 26

examples of epigenetic mechanisms

Answer 26

alter chromatin structure, affect gene expression

reversible, post-translational modifications of histones and DNA methylation

Question 27

genetic imprinting

Answer 27

sex-dependent epigenetic modulation of regulatory regions such as promoter sequences
paternally/maternally imprinted

Question 28

DNA methylation as mediator of genetic imprinting

Answer 28

marks are established in gamete
stably maintained in somatic cells after fertilization
reversible
reset during gametogenesis to transmit appropriate sex-specific imprint to progeny

Question 29

where does somatic maintenance of imprinted regions occur?

Answer 29

in somatic cells

Question 30

epigenetic memory

Answer 30

establish new epigenetic markers based on if sperm or oocyte

Question 31

gametogenesis in absence of erasure and resetting

Answer 31

embryos with no active copies, or two active copies, of imprinted genes would be produced at high frequencies
imbalance in gene expression/imprinting

Question 32

how are deletions caused?

Answer 32

• result from repeat misalignments
• in PWS/AS they result from presence of low copy repeats in vicinity of the common breakpoints in patients, derived from large genomic duplications of gene HERC2.

Question 33

what can prader willi result from?

Answer 33

uniparental disomy

2 maternal imprinted chromosomes since had nondisjunction event and male gamete was kicked out.