Chromosomes

Question 1

What are fragile sites

Answer 1

Segments of uncoiled chromatin liable to show gaps and breaks, low gene content, high LINES, arise when cells exposed to conditions damaging the Dna repair process

Question 2

Which fragile sites are pathogenic

Answer 2

FraxA Xq27.3 and FraxE Xq28

Question 3

How are fragile sites classified?

Answer 3

Frequency and culture conditions.

Question 4

Properties of constitutive heterochromatin

Answer 4

AT rich, inert satellite Dna, dark c band

Question 5

What causes heterochromatin variation

Answer 5

Instability of satellite Dna

Question 6

Role of alpha satellite Dna

Answer 6

Centromere development, facilitate proper segregation

Question 7

3 types of satellite dna

Answer 7

Alpha: 3/5% human genome, role in centromere development and proper segregation. Beta and gamma: on X chromosome, has role in preventing heterochromatin spreading

Question 8

Example of inversion variant

Answer 8

Inv(9)(p11q12), inv(2)(p11.2q13), inv(y)(p11.2q11.2)

Question 9

What are uBCAs

Answer 9

Directly transmitted unbalanced Chr abnormalities . Copy number of multiple genes increase or decrease by 1. Unique to family. Compatible with fertility. 5,8,18 most freq.

Question 10

Example of euchromatic variant

Answer 10

Var(16)(p11.2p11.2)verse blue duo of dark g band 16p11.2. Additional copies of cassette. Normal =4 EV=10-12

Question 11

What is a euchromatic variant EV

Answer 11

Cnv of segments polymorphic in population and only detectable when reach certain number of copies. Resemble dups.

Question 12

Frequency of autosomal reciprocal translocation

Answer 12

1:500

Question 13

How do you risk assess outcome of balanced translocation

Answer 13

Literature eg Schinzel, ecaruca, size of segment, de novo?, which chromosome? HAL

Question 14

Freq of robertsonians

Answer 14

1:1000

Question 15

Risks to robertsonian carrier

Answer 15

Upd, unbalanced offspring in female carriers 10-15%, in male carriers

Question 16

Impact of sex Chr ; autosomal translocation

Answer 16

Disrupt sex vesicle can cause infertility

Question 17

Possible outcome from a balanced paracentric inversion

Answer 17

Unequal XO in loop-> dicentric and acentric , XO outside loop -> normal and balanced

Question 18

Outcomes from peri centric inversion

Answer 18

Outside loop-> normal and balanced, inside loop-> normal, balanced, recdup p and recdup q

Question 19

Risk of abnormal offspring from inter chromosomal insertion

Answer 19

50% (live born risk depend on size of imbalance)

Question 20

Risk from intrachromosomal insertion

Answer 20

Small ins 20-30%, large ins 5-10%

Question 21

Freq of insertions

Answer 21

1:80,000

Question 22

Outcomes from interchromosomal insertion

Answer 22

Small-> independent synapsing and get normal,balanced, del,dup. Large-> forms quadrivalent and recombinant chromosomes.

Question 23

What are lcr’s

Answer 23

Low copy repeats, unstable architecture and permit Dna recombinations via nahr.

Question 24

What is a contiguous gene syndrome

Answer 24

Loss/gain multiple adjacent genes

Question 25

What are low copy repeats

Answer 25

10-400kb, >97% homology, low numbers in genome- 5-10%

Question 26

Syndromes mediated by lcr’s

Answer 26

Williams, pws/as, sms/ptls

Question 27

Possible origins of structural rearrangements

Answer 27

Nhej, mmej, Bfb cycle, FoStes, mmbir, chromothripsis

Question 28

What is most common human translocation

Answer 28

T(11;22)(q23;q11)

Question 29

Mechanism of robertsonian formation

Answer 29

Centric fusion, whole arm translocation, break in both arms (dicentric), misdivision of centromere, u true exchange -> isochromosome

Question 30

Clinical relevant isodicentrics

Answer 30

Idic(22)(q11.2) cat eye syndrome, idic(15q)

Question 31

Meiosis errors

Answer 31

Anaphase lag, premature sister chromatid separation, non disjunction

Question 32

G band dark band characteristics

Answer 32

Heterochromatin, gene poor, low histone acetylation, LINES

Question 33

G band light characteristics

Answer 33

Euchromatic, GC rich, height histone acetylation, sines

Question 34

List normal variation seen on human chromosomes

Answer 34

Het variation. Satellite variation. Inversion variants eg 9,2. Fragile sites. uBCAs. Euchromatic variant eg var(16)(p11.2p11.2)

Question 35

Which is most common SMC

Answer 35

Idic(15) most common region duo q11-13 including pwacr.. Severe DD, autism, epilepsy. Ass with AMA.

Question 36

Causes and % of each for T18

Answer 36

90% Maternal NDJ meiosis, 5% paternal meiotic NDJ, 5% mosaic

Question 37

Example of emerging microdel syndrome

Answer 37

19p13.2. 7n, shirt, heart, scoliosis, early puberty, DD, language delay

Question 38

Location DSCR

Answer 38

21q22.3

Question 39

Origins and % of errors leading to Down syndrome

Answer 39

70% maternal meiosis 1. 20% mat meiosis 2. 5% pat meiosis, 5% mosaic

Question 40

Freq of ABCR

Answer 40

1/500

Question 41

How can ABCR lead to abnormal phenotype

Answer 41

Gene disruption at bkpts. Cryptic imbalance. Position effect. Disturb imprinting. Upd. Xi. Mosaicism. IF,

Question 42

ACGH has shown many ABCR are actually cryptically unbalanced - what % of 2 break and CCR are unbalanced

Answer 42

2 break 37% and CCR 90%. This imbalance could be at breakpoints or elsewhere

Question 43

What is position effect variegation (PEV)

Answer 43

Variable but stable inhibition of gene exp due to juxtaposition of euchromatic gene with heterochromatin. Het spreads and silences gene.

Question 44

% markers derived from acrocentric X

Answer 44

70%

Question 45

% markers seen in sub fertile popn

Answer 45

0.125% 3x higher than general pop

Question 46

Example of new marker related syndrome

Answer 46

+der(22)t(8;22). One of few recurrent human translations. Ear and extremity abnormalities, mild mr. Variable phenotype. Sheridan et al 2010

Question 47

Examples of marker syndromes

Answer 47

i12p, i(18p), +der(22)t(11;22), idic(15), ces invdup (22q11.2-pter)