large structural rearrangements

Question 1

why are rearrangements usually transmitted through maternal line?

Answer 1

spermatogenesis is inhibited by large structural rearrangements

Question 2

what is a robertsonian translocation

Answer 2

an unbalanced rearrangement between two acrocentric chromosomes

Question 3

what is a non-homologus robertsonian translocation?

Answer 3

q arm of one chromome fused to q arm of another- 10 possible combinations

Question 4

what is a homologus robertsonian translocation

Answer 4

2 q arms of the same chromosome fuse- only 5 possible translocations

Question 5

why is the loss of chromsosome part tolerated?

Answer 5

p arm of acrocentrics contains lots of repteitive sequences

Question 6

what is the distribution of non-homologous robertsonian translocations?

Answer 6

non-random. 76% are 13;14, 10% 14;21 and the rest are evenly distributed throughout the remaining 8 translocations

Question 7

what do nuclear organiser regions on p12 do?

Answer 7

allow all acrocentric chromosomes to come together at nucleolous

Question 8

why is it likely that the ds breaks will occur in the nucleolous?

Answer 8

high level of free radicals, transcription and replication

Question 9

where are the majority of breakpoints in robertsonian translocations?

Answer 9

proximal to the NOR

Question 10

how are 13;14 and 14;21 translocations formed?

Answer 10

fusion site for 13;14 and 14;21 are basically homogenous so most likely get homologous recombination between repetitive sequences in opposite direction

Question 11

how is the orientation of p11.2 satellites important?

Answer 11

there are 4 microsatellites, if they are inverted then will get a dicentric chromosome formed. one centromere is deactivated

Question 12

what are the 3 possible products from a robertsonian translocation segragation in meiosis I?

Answer 12

• 2 normal, 2 balanced robertsonians 14;21
• 2 disomic 21 and 2 nullisomic 21
• 2 disomic 14, 2 nullisomic 14

Question 13

what can affect the risk of a child being abnormal for downs?

Answer 13

robertsonian translocations have increased meiotic NDJ likleyhood, also need to account for trisomy and monosomy rescue events, advanced maternal age, adormalities of other chromosomes could also result in NDJ, issues regarding UPD

Question 14

what is Uni parental isodisomy?

Answer 14

2 copies of the same chromosome from one parent

Question 15

how does UPD occur?

Answer 15

trisomy rescue or gamete complementation

Question 16

how does UPID occur?

Answer 16

monosomic rescue, gamete complementation

Question 17

what are robertsonian translocation carriers at higher risk of?

Answer 17

UPD pregnancies, as predisposed to aneuploid gamete formation

Question 18

how do UPD and UPID result in disease?

Answer 18

LOH- loses the gene in a chromosome so results in recessive disease. or if chromosomes imprinted

Question 19

how can structural rearrangements be transmitted?

Answer 19

errors in meiosis late in spermatogeneis can result in a translocation that is mosaic

Question 20

if neither parent carries the abnormality how many the translocation have arisen?

Answer 20

de novo from mitotic NDJ

Question 21

what is a recurrent translcoation?

Answer 21

where translocations appear in individuals in the population that are not related

Question 22

what is the most common recurrent translocation? what are the breakpoints?

Answer 22

(11;22)(q23;q11) AT rich palindromic repeat breakpoints

Question 23

what does this recurrent translocation increase the risk of what disease?

Answer 23

Emanuel

Question 24

what is emanuel syndrome caused by?

Answer 24

3:1 malsegregation of chromosome 22 and the supernumary inheritance of this derivative chromosome. 2 normal chromosome 11 and 22 and derivative one fromed from a translocation between 11 and 22

Question 25

what are the symptoms of emanuels

Answer 25

mental retardation, morphological features eg cleft lip pallete, small head, genital defects. kidney and heart abnormalities

Question 26

what are 30% of oligo and azoospermia due to?

Answer 26

AZFa, AZFb and AZFc genes on Y chromosome. deletion of these genes occurs due to homolgous recombination

Question 27

what can make translocations more likley? (3)

Answer 27

repetitive sequences, longer length of homology between repetitive sequences and shorter distance between the repetitive sequences

Question 28

what is a pachytene cross?

Answer 28

where the 4 chromosomes pair together in meiosis I

Question 29

what gametes are made in alternate segregation?

Answer 29

alternate centromere segreagate together- 2 normal and 2 with balanced translocations

Question 30

what gametes are made in adjacent I segregation?

Answer 30

non-homologous adjacent centromere segregate toegther- unbalanced gametes

Question 31

what gametes are made in adjacent II segregation?

Answer 31

adjacent homologous centromere segreagte together- v unbalanced gametes made

Question 32

how do PATRRs cause instability in the genome?

Answer 32

suspetible to mispairing leading to formation of secondaruy structures which cause instability

Question 33

how are 11;22 translocations thought to happen?

Answer 33

colocalisation of PATRR11 and PATRR22 during late spermatogenesis then get DSB and subequent repir by NHEJ